41 research outputs found

    NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

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    Xenarthrans – anteaters, sloths, and armadillos – have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with 24 domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, ten anteaters, and six sloths. Our dataset includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data-paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the south of the USA, Mexico, and Caribbean countries at the northern portion of the Neotropics, to its austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n=5,941), and Cyclopes sp. has the fewest (n=240). The armadillo species with the most data is Dasypus novemcinctus (n=11,588), and the least recorded for Calyptophractus retusus (n=33). With regards to sloth species, Bradypus variegatus has the most records (n=962), and Bradypus pygmaeus has the fewest (n=12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other datasets of Neotropical Series which will become available very soon (i.e. Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans dataset

    Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

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    BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

    Consistent patterns of common species across tropical tree communities

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    Trees structure the Earth’s most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations1,2,3,4,5,6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth’s 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world’s most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees

    Open data from the third observing run of LIGO, Virgo, KAGRA, and GEO

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    The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in 2019 April and lasting six months, O3b starting in 2019 November and lasting five months, and O3GK starting in 2020 April and lasting two weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main data set, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages

    Mitochondria And Reactive Oxygen Species

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    Mitochondria are a quantitatively relevant source of reactive oxygen species (ROS) in the majority of cell types. Here we review the sources and metabolism of ROS in this organelle, including the conditions that regulate the production of these species, such as mild uncoupling, oxygen tension, respiratory inhibition, Ca2+ and K+ transport, and mitochondrial content and morphology. We discuss substrate-, tissue-, and organism-specific characteristics of mitochondrial oxidant generation. Several aspects of the physiological and pathological roles of mitochondrial ROS production are also addressed. © 2009 Elsevier Inc. All rights reserved.474333343Hinkle, P.C., Butow, R.A., Racker, E., Chance, B., Partial resolution of the enzymes catalyzing oxidative phosphorylation. XV. Reverse electron transfer in the flavin-cytochrome beta region of the respiratory chain of beef heart submitochondrial particles (1967) J. Biol. Chem., 242, pp. 5169-5173Jensen, P.K., Antimycin-insensitive oxidation of succinate and reduced nicotinamide-adenine dinucleotide in electron-transport particles. I. pH dependency and hydrogen peroxide formation (1966) Biochim. Biophys. Acta, 122, pp. 157-166Loschen, G., Azzi, A., Flohé, L., Mitochondrial H2O2 formation: relationship with energy conservation (1973) FEBS Lett., 33, pp. 84-87Boveris, A., Cadenas, E., Mitochondrial production of superoxide anions and its relationship to the antimycin insensitive respiration (1975) FEBS Lett., 54, pp. 311-314Forman, H.J., Kennedy, J.A., Role of superoxide radical in mitochondrial dehydrogenase reactions (1974) Biochem. Biophys. Res. Commun., 60, pp. 1044-1050Loschen, G., Azzi, A., Richter, C., Flohé, L., Superoxide radicals as precursors of mitochondrial hydrogen peroxide (1974) FEBS Lett., 42, pp. 68-72Weisiger, R.A., Fridovich, I., Superoxide dismutase: organelle specificity (1973) J. Biol. Chem., 248, pp. 3582-3592Weisiger, R.A., Fridovich, I., Mitochondrial superoxide simutase: site of synthesis and intramitochondrial localization (1973) J. Biol. Chem., 248, pp. 4793-4796Dröge, W., Free radicals in the physiological control of cell function (2002) Physiol. Rev., 82, pp. 47-95Fridovich, I., Superoxide radical and superoxide dismutases (1995) Annu. Rev. Biochem., 64, pp. 97-112Okado-Matsumoto, A., Fridovich, I., Subcellular distribution of superoxide dismutases (SOD) in rat liver: Cu,Zn-SOD in mitochondria (2001) J. Biol. Chem., 276, pp. 38388-38393Liu, Y., Fiskum, G., Schubert, D., Generation of reactive oxygen species by the mitochondrial electron transport chain (2002) J. Neurochem., 80, pp. 780-787Lambertucci, R.H., Hirabara, S.M., Silveira, L.D.R., Levada-Pires, A.C., Curi, R., Pithon-Curi, T.C., Palmitate increases superoxide production through mitochondrial electron transport chain and NADPH oxidase activity in skeletal muscle cells (2008) J. Cell. Physiol., 216, pp. 796-804Tretter, L., Takacs, K., Hegedus, V., Adam-Vizi, V., Characteristics of alpha-glycerophosphate-evoked H2O2 generation in brain mitochondria (2007) J. Neurochem., 100, pp. 650-663Tretter, L., Takacs, K., Kövér, K., Adam-Vizi, V., Stimulation of H2O2 generation by calcium in brain mitochondria respiring on alpha-glycerophosphate (2007) J. Neurosci. Res., 85, pp. 3471-3479Lenaz, G., The mitochondrial production of reactive oxygen species: mechanisms and implications in human pathology (2001) IUBMB Life, 52, pp. 159-164Starkov, A.A., Fiskum, G., Chinopoulos, C., Lorenzo, B.J., Browne, S.E., Patel, M.S., Beal, M.F., Mitochondrial alpha-ketoglutarate dehydrogenase complex generates reactive oxygen species (2004) J. Neurosci., 24, pp. 7779-7788Tretter, L., Adam-Vizi, V., Generation of reactive oxygen species in the reaction catalyzed by alpha-ketoglutarate dehydrogenase (2004) J. Neurosci., 24, pp. 7771-7778Tahara, E.B., Barros, M.H., Oliveira, G.A., Netto, L.E.S., Kowaltowski, A.J., Dihydrolipoyl dehydrogenase as a source of reactive oxygen species inhibited by caloric restriction and involved in Saccharomyces cerevisiae aging (2007) FASEB J., 21, pp. 274-283Johnson, D.T., Harris, R.A., French, S., Blair, P.V., You, J., Bemis, K.G., Wang, M., Balaban, R.S., Tissue heterogeneity of the mammalian mitochondrial proteome (2007) Am. J. Physiol. Cell Physiol., 292, pp. C689-697Johnson, D.T., Harris, R.A., Blair, P.V., Balaban, R.S., Functional consequences of mitochondrial proteome heterogeneity (2007) Am. J. Physiol. Cell Physiol., 292, pp. C698-707Sturtz, L.A., Diekert, K., Jensen, L.T., Lill, R., Culotta, V.C.A., fraction of yeast Cu,Zn-superoxide dismutase and its metallochaperone, CCS, localize to the intermembrane space of mitochondria: a physiological role for SOD1 in guarding against mitochondrial oxidative damage (2001) J. Biol. Chem., 276, pp. 38084-38089Santiago, A.P.S.A., Chaves, E.A., Oliveira, M.F., Galina, A., Reactive oxygen species generation is modulated by mitochondrial kinases: correlation with mitochondrial antioxidant peroxidases in rat tissues (2008) Biochimie, 90, pp. 1566-1577Tahara, E.B., Navarete, F.D., Kowaltowski, A.J., Tissue-, substrate-, and site-specific characteristics of mitochondrial reactive oxygen species generation (2009) Free Radic. Biol. Med., 46, pp. 1283-1297Capel, F., Rimbert, V., Lioger, D., Diot, A., Rousset, P., Mirand, P.P., Boirie, Y., Mosoni, L., Due to reverse electron transfer, mitochondrial H2O2 release increases with age in human vastus lateralis muscle although oxidative capacity is preserved (2005) Mech. Ageing Dev., 126, pp. 505-511Fornazari, M., de Paula, J.G., Castilho, R.F., Kowaltowski, A.J., Redox properties of the adenoside triphosphate-sensitive K+ channel in brain mitochondria (2008) J. Neurosci. Res., 86, pp. 1548-1556Grivennikova, V.G., Vinogradov, A.D., Generation of superoxide by the mitochondrial complex I (2006) Biochim. Biophys. Acta, 1757, pp. 553-561Barros, M.H., Bandy, B., Tahara, E.B., Kowaltowski, A.J., Higher respiratory activity decreases mitochondrial reactive oxygen release and increases life span in Saccharomyces cerevisiae (2004) J. Biol. Chem., 279, pp. 49883-49888Oliveira, G.A., Tahara, E.B., Gombert, A.K., Barros, M.H., Kowaltowski, A.J., Increased aerobic metabolism is essential for the beneficial effects of caloric restriction on yeast life span (2008) J. Bioenerg. Biomembr., 40, pp. 381-388Cavalheiro, R.A., Fortes, F., Borecký, J., Faustinoni, V.C., Schreiber, A.Z., Vercesi, A.E., Respiration, oxidative phosphorylation, and uncoupling protein in Candida albicans (2004) Braz. J. Med. Biol. Res., 37, pp. 1455-1461Jarmuszkiewicz, W., Milani, G., Fortes, F., Schreiber, A.Z., Sluse, F.E., Vercesi, A.E., First evidence and characterization of an uncoupling protein in Fungi kingdom: cpUCP of Candida parapsilosis (2000) FEBS Lett., 467, pp. 145-149Milani, G., Jarmuszkiewicz, W., Sluse-Goffart, C.M., Schreiber, A.Z., Vercesi, A.E., Sluse, F.E., Respiratory chain network in mitochondria of Candida parapsilosis: ADP/O appraisal of the multiple electron pathways (2001) FEBS Lett., 508, pp. 231-235Lebovitz, R.M., Zhang, H., Vogel, H., Cartwright, J.J., Dionne, L., Lu, N., Huang, S., Matzuk, M.M., Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice (1996) Proc. Natl. Acad. Sci. USA, 93, pp. 9782-9787Ruy, F., Vercesi, A.E., Kowaltowski, A.J., Inhibition of specific electron transport pathways leads to oxidative stress and decreased Candida albicans proliferation (2006) J. Bioenerg. Biomembr., 38, pp. 129-135Affourtit, C., Krab, K., Moore, A.L., Control of plant mitochondrial respiration (2001) Biochim. Biophys. Acta, 1504, pp. 58-69Almeida, A.M., Navet, R., Jarmuszkiewicz, W., Vercesi, A.E., Sluse-Goffart, C.M., Sluse, F.E., The energy-conserving and energy-dissipating processes in mitochondria isolated from wild type and nonripening tomato fruits during development on the plant (2002) J. Bioenerg. Biomembr., 34, pp. 487-498Borecky, J., Nogueira, F.T.S., de Oliveira, K.A.P., Maia, I.G., Vercesi, A.E., Arruda, P., The plant energy-dissipating mitochondrial systems: depicting the genomic structure and the expression profiles of the gene families of uncoupling protein and alternative oxidase in monocots and dicots (2006) J. Exp. Bot., 57, pp. 849-864Borecký, J., Vercesi, A.E., Plant uncoupling mitochondrial protein and alternative oxidase: energy metabolism and stress (2005) Biosci. Rep., 25, pp. 271-286Brandalise, M., Maia, I.G., Borecký, J., Vercesi, A.E., Arruda, P., Overexpression of plant uncoupling mitochondrial protein in transgenic tobacco increases tolerance to oxidative stress (2003) J. Bioenerg. Biomembr., 35, pp. 203-209Clifton, R., Millar, A.H., Whelan, J., Alternative oxidases in Arabidopsis: a comparative analysis of differential expression in the gene family provides new insights into function of non-phosphorylating bypasses (2006) Biochim. Biophys. Acta, 1757, pp. 730-741Costa, A.D., Nantes, I.L., Jezek, P., Leite, A., Arruda, P., Vercesi, A.E., Plant uncoupling mitochondrial protein activity in mitochondria isolated from tomatoes at different stages of ripening (1999) J. Bioenerg. Biomembr., 31, pp. 527-533Vercesi, A., Martins, I., Silva, M., Leite, H., Cuccovia, I., Chalmovich, H., Pumping plants (1995) Nature, 375, p. 24Vercesi, A.E., Borecký, J., Maia, I.D.G., Arruda, P., Cuccovia, I.M., Chaimovich, H., Plant uncoupling mitochondrial proteins (2006) Annu. Rev. Plant Biol., 57, pp. 383-404Li, Y., Huang, T.T., Carlson, E.J., Melov, S., Ursell, P.C., Olson, J.L., Noble, L.J., Epstein, C.J., Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase (1995) Nat. Genet., 11, pp. 376-381Sluse, F.E., Jarmuszkiewicz, W., Uncoupling proteins outside the Animal and Plant kingdoms: functional and evolutionary aspects (2002) FEBS Lett., 510, pp. 117-120Brookes, P.S., Mitochondrial H+ leak and ROS generation: an odd couple (2005) Free Radic. Biol. Med., 38, pp. 12-23Caldeira da Silva, C.C., Cerqueira, F.M., Barbosa, L.F., Medeiros, M.H.G., Kowaltowski, A.J., Mild mitochondrial uncoupling in mice affects energy metabolism, redox balance and longevity (2008) Aging Cell, 7, pp. 552-560Korshunov, S.S., Skulachev, V.P., Starkov, A.A., High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria (1997) FEBS Lett., 416, pp. 15-18Kowaltowski, A.J., Costa, A.D., Vercesi, A.E., Activation of the potato plant uncoupling mitochondrial protein inhibits reactive oxygen species generation by the respiratory chain (1998) FEBS Lett., 425, pp. 213-216Popov, V.N., Simonian, R.A., Skulachev, V.P., Starkov, A.A., Inhibition of the alternative oxidase stimulates H2O2 production in plant mitochondria (1997) FEBS Lett., 415, pp. 87-90Skulachev, V.P., Uncoupling: new approaches to an old problem of bioenergetics (1998) Biochim. Biophys. Acta, 1363, pp. 100-124Czarna, M., Jarmuszkiewicz, W., Activation of alternative oxidase and uncoupling protein lowers hydrogen peroxide formation in amoeba Acanthamoeba castellanii mitochondria (2005) FEBS Lett., 579, pp. 3136-3140Ferranti, R., da Silva, M.M., Kowaltowski, A.J., Mitochondrial ATP-sensitive K+ channel opening decreases reactive oxygen species generation (2003) FEBS Lett., 536, pp. 51-55Nègre-Salvayre, A., Hirtz, C., Carrera, G., Cazenave, R., Troly, M., Salvayre, R., Pénicaud, L., Casteilla, L., A role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation (1997) FASEB J., 11, pp. 809-815Melov, S., Doctrow, S.R., Schneider, J.A., Haberson, J., Patel, M., Coskun, P.E., Huffman, K., Malfroy, B., Lifespan extension and rescue of spongiform encephalopathy in superoxide dismutase 2 nullizygous mice treated with superoxide dismutase-catalase mimetics (2001) J. Neurosci., 21, pp. 8348-8353Facundo, H.T.F., Carreira, R.S., de Paula, J.G., Santos, C.C.X., Ferranti, R., Laurindo, F.R.M., Kowaltowski, A.J., Ischemic preconditioning requires increases in reactive oxygen release independent of mitochondrial K+ channel activity (2006) Free Radic. Biol. Med., 40, pp. 469-479Vanden Hoek, T., Becker, L.B., Shao, Z.H., Li, C.Q., Schumacker, P.T., Preconditioning in cardiomyocytes protects by attenuating oxidant stress at reperfusion (2000) Circ. Res., 86, pp. 541-548Echtay, K.S., Brand, M., D. 4-Hydroxy-2-nonenal and uncoupling proteins: an approach for regulation of mitochondrial ROS production (2007) Redox Rep., 12, pp. 26-29Echtay, K.S., Roussel, D., St-Pierre, J., Jekabsons, M.B., Cadenas, S., Stuart, J.A., Harper, J.A., Brand, M.D., Superoxide activates mitochondrial uncoupling proteins (2002) Nature, 415, pp. 96-99Echtay, K.S., Murphy, M.P., Smith, R.A.J., Talbot, D.A., Brand, M.D., Superoxide activates mitochondrial uncoupling protein 2 from the matrix side: studies using targeted antioxidants (2002) J. Biol. Chem., 277, pp. 47129-47135Costa, A.D.T., Garlid, K.D., Intramitochondrial signaling: interactions among mitoKATP, PKCepsilon, ROS, and MPT (2008) Am. J. Physiol. Heart Circ. Physiol., 295, pp. H874-H882Zhang, D.X., Chen, Y.F., Campbell, W.B., Zou, A.P., Gross, G.J., Li, P.L., Characteristics and superoxide-induced activation of reconstituted myocardial mitochondrial ATP-sensitive potassium channels (2001) Circ. Res., 89, pp. 1177-1183Rhoads, D.M., Umbach, A.L., Sweet, C.R., Lennon, A.M., Rauch, G.S., Siedow, J.N., Regulation of the cyanide-resistant alternative oxidase of plant mitochondria: identification of the cysteine residue involved in alpha-keto acid stimulation and intersubunit disulfide bond formation (1998) J. Biol. Chem., 273, pp. 30750-30756Jezek, P., Engstová, H., Zácková, M., Vercesi, A.E., Costa, A.D., Arruda, P., Garlid, K.D., Fatty acid cycling mechanism and mitochondrial uncoupling proteins (1998) Biochim. Biophys. Acta, 1365, pp. 319-327Alberici, L.C., Oliveira, H.C.F., Patrício, P.R., Kowaltowski, A.J., Vercesi, A.E., Hyperlipidemic mice present enhanced catabolism and higher mitochondrial ATP-sensitive K+ channel activity (2006) Gastroenterology, 131, pp. 1228-1234Bienert, G.P., Schjoerring, J.K., Jahn, T.P., Membrane transport of hydrogen peroxide (2006) Biochim. Biophys. Acta, 1758, pp. 994-1003Paucek, P., Yarov-Yarovoy, V., Sun, X., Garlid, K.D., Inhibition of the mitochondrial KATP channel by long-chain acyl-CoA esters and activation by guanine nucleotides (1996) J. Biol. Chem., 271, pp. 32084-32088Meyer, L.E., Machado, L.B., Santiago, A.P.S.A., da-Silva, W.S., De Felice, F.G., Holub, O., Oliveira, M.F., Galina, A., Mitochondrial creatine kinase activity prevents reactive oxygen species generation: antioxidant role of mitochondrial kinase-dependent ADP re-cycling activity (2006) J. Biol. Chem., 281, pp. 37361-37371da-Silva, W.S., Gómez-Puyou, A., de Gómez-Puyou, M.T., Moreno-Sanchez, R., De Felice, F.G., de Meis, L., Oliveira, M.F., Galina, A., Mitochondrial bound hexokinase activity as a preventive antioxidant defense: steady-state ADP formation as a regulatory mechanism of membrane potential and reactive oxygen species generation in mitochondria (2004) J. Biol. Chem., 279, pp. 39846-39855Andersen, J.K., Oxidative stress in neurodegeneration: cause or consequence? (2004) Nat. Med., 10, pp. S18-25Calabrese, V., Lodi, R., Tonon, C., D'Agata, V., Sapienza, M., Scapagnini, G., Mangiameli, A., Butterfield, D.A., Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich's ataxia (2005) J. Neurol. Sci., 233, pp. 145-162Fiskum, G., Mitochondrial participation in ischemic and traumatic neural cell death (2000) J. Neurotrauma, 17, pp. 843-855Fukui, H., Moraes, C.T., The mitochondrial impairment, oxidative stress and neurodegeneration connection: reality or just an attractive hypothesis? (2008) Trends Neurosci., 31, pp. 251-256Geromel, V., Kadhom, N., Cebalos-Picot, I., Ouari, O., Polidori, A., Munnich, A., Rötig, A., Rustin, P., Superoxide-induced massive apoptosis in cultured skin fibroblasts harboring the neurogenic ataxia retinitis pigmentosa (NARP) mutation in the ATPase-6 gene of the mitochondrial DNA (2001) Hum. Mol. Genet., 10, pp. 1221-1228Sousa, S.C., Castilho, R.F., Protective effect of melatonin on rotenone plus Ca2+-induced mitochondrial oxidative stress and PC12 cell death (2005) Antioxid. Redox Signaling, 7, pp. 1110-1116Kowaltowski, A.J., Vercesi, A.E., Mitochondrial damage induced by conditions of oxidative stress (1999) Free Radic. Biol. Med., 26, pp. 463-471Lee, W.K., Thévenod, F., A role for mitochondrial aquaporins in cellular life-and-death decisions? (2006) Am. J. Physiol. Cell Physiol., 291, pp. 195-202Birket, M.J., Passos, J.F., von Zglinicki, T., Birch-Machin, M.A., The relationship between the aging- and photo-dependent T414G mitochondrial DNA mutation with cellular senescence and reactive oxygen species production in cultured skin fibroblasts (2009) J. Invest. Dermatol., 129, pp. 1361-1366Gonzalo, R., Garcia-Arumi, E., Llige, D., Marti, R., Solano, A., Montoya, J., Arenas, J., Andreu, A.L., Free radicals-mediated damage in transmitochondrial cells harboring the T14487C mutation in the ND6 gene of mtDNA (2005) FEBS Lett., 579, pp. 6909-6913Li, J., Zhou, K., Meng, X., Wu, Q., Li, S., Liu, Y., Wang, J., Increased ROS generation and SOD activity in heteroplasmic tissues of transmitochondrial mice with A3243G mitochondrial DNA mutation (2008) Genet. Mol. Res., 7, pp. 1054-1062Menzies, K.J., Robinson, B.H., Hood, D.A., Effect of thyroid hormone on mitochondrial properties and oxidative stress in cells from paHolmgren, A., Antioxidant function of thioredoxin and glutaredoxin systems (2000) Antioxid. Redox Signaling, 2, pp. 811-820Nordberg, J., Arnér, E.S., Reactive oxygen species, antioxidants, and the mammalian thioredoxin system (2001) Free Radic. Biol. Med., 31, pp. 1287-1312Dalton, T.P., Shertzer, H.G., Puga, A., Regulation of gene expression by reactive oxygen (1999) Annu. Rev. Pharmacol. Toxicol., 39, pp. 67-101Carreira, R.S., Miyamoto, S., Di Mascio, P., Gonçalves, L.M., Monteiro, P., Providência, L.A., Kowaltowski, A.J., Ischemic preconditioning enhances fatty acid-dependent mitochondrial uncoupling (2007) J. Bioenerg. Biomembr., 39, pp. 313-320Facundo, H.T.F., de Paula, J.G., Kowaltowski, A.J., Mitochondrial ATP-sensitive K+ channels are redox-sensitive pathways that control reactive oxygen species production (2007) Free Radic. Biol. Med., 42, pp. 1039-1048Talbot, D.A., Hanuise, N., Rey, B., Rouanet, J., Duchamp, C., Brand, M.D., Superoxide activates a GDP-sensitive proton conductance in skeletal muscle mitochondria from king penguin (Aptenodytes patagonicus) (2003) Biochem. Biophys. Res. Commun., 312, pp. 983-988Talbot, D.A., Lambert, A.J., Brand, M.D., Production of endogenous matrix superoxide from mitochondrial complex I leads to activation of uncoupling protein 3 (2004) FEBS Lett., 556, pp. 111-115Radi, R., Turrens, J.F., Chang, L.Y., Bush, K.M., Crapo, J.D., Freeman, B.A., Detection of catalase in rat heart mitochondria (1991) J. Biol. Chem., 266, pp. 22028-22034Salvi, M., Battaglia, V., Brunati, A.M., La Rocca, N., Tibaldi, E., Pietrangeli, P., Marcocci, L., Toninello, A., Catalase takes part in rat liver mitochondria oxidative stress defense (2007) J. Biol. Chem., 282, pp. 24407-24415Petrova, V.Y., Drescher, D., Kujumdzieva, A.V., Schmitt, M.J., Dual targeting of yeast catalase A to peroxisomes and mitochondria (2004) Biochem. J., 380, pp. 393-400Arnér, E.S., Holmgren, A., Physiological functions of thioredoxin and thioredoxin reductase (2000) Eur. J. Biochem., 267, pp. 6102-6109Hofmann, B., Hecht, H., Flohé, L., Peroxiredoxins (2002) Biol. Chem., 383, pp. 347-364Pedrajas, J.R., Miranda-Vizuete, A., Javanmardy, N., Gustafsson, J.A., Spyrou, G., Mitochondria of Saccharomyces cerevisiae contain one-conserved cysteine type peroxiredoxin with thioredoxin peroxidase activity (2000) J. Biol. Chem., 275, pp. 16296-16301Monteiro, G., Horta, B.B., Pimenta, D.C., Augusto, O., Netto, L.E.S., Reduction of 1-Cys peroxiredoxins by ascorbate changes the thiol-specific antioxidant paradigm, revealing another function of vitamin C (2007) Proc. Natl. Acad. Sci. USA, 104, pp. 4886-4891Rydström, J., Mitochondrial NADPH, transhydrogenase and disease (2006) Biochim. Biophys. Acta, 1757, pp. 721-726Castilho, R.F., Kowaltowski, A.J., Meinicke, A.R., Bechara, E.J., Vercesi, A.E., Permeabilization of the inner mitochondrial membrane by Ca2+ ions is stimulated by t-butyl hydroperoxide and mediated by reactive oxygen species generated by mitochondria (1995) Free Radic. Biol. Med., 18, pp. 479-486Kowaltowski, A.J., Castilho, R.F., Vercesi, A.E., Mitochondrial permeability transition and oxidative stress (2001) FEBS Lett., 495, pp. 12-15Lehninger, A.L., Vercesi, A., Bababunmi, E.A., Regulation of Ca2+ release from mitochondria by the oxidation-reduction state of pyridine nucleotides (1978) Proc. Natl. Acad. Sci. USA, 75, pp. 1690-1694Lemasters, J.J., Nieminen, A.L., Qian, T., Trost, L.C., Herman, B., The mitochondrial permeability transition in toxic, hypoxic and reperfusion injury (1997) Mol. Cell. Biochem., 174, pp. 159-165Vercesi, A.E., Pereira-da-Silva, L., NADP redox state and mitochondrial Ca2+ efflux: a controversial issue (1984) Braz. J. Med. Biol. Res., 17, pp. 353-356Zoratti, M., Szabò, I., The mitochondrial permeability transition (1995) Biochim. Biophys. Acta, 1241, pp. 139-176Sazanov, L.A., Jackson, J.B., Proton-translocating transhydrogenase and NAD- and NADP-linked isocitrate dehydrogenases operate in a substrate cycle which contributes to fine regulation of the tricarboxylic acid cycle activity in mitochondria (1994) FEBS Lett., 344, pp. 109-116Jo, S.H., Son, M.K., Koh, H.J., Lee, S.M., Song, I.H., Kim, Y.O., Lee, Y.S., Huh, T.L., Control of mitochondrial redox balance and cellular defense against oxidative damage by mitochondrial NADP+-dependent isocitrate dehydrogenas

    Protective Effects Of L-carnitine And Piracetam Against Mitochondrial Permeability Transition And Pc3 Cell Necrosis Induced By Simvastatin

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    Mitochondrial oxidative stress followed by membrane permeability transition (MPT) has been considered as a possible mechanism for statins cytotoxicity. Statins use has been associated with reduced risk of cancer incidence, especially prostate cancer. Here we investigated the pathways leading to simvastatin-induced prostate cancer cell death as well as the mechanisms of cell death protection by l-carnitine or piracetam. These compounds are known to prevent and/or protect against cell death mediated by oxidative mitochondrial damage induced by a variety of conditions, either in vivo or in vitro. The results provide evidence that simvastatin induced MPT and cell necrosis were sensitive to either l-carnitine or piracetam in a dose-dependent fashion and mediated by additive mechanisms. When combined, l-carnitine and piracetam acted at concentrations significantly lower than they act individually. These results shed new light into both the cytotoxic mechanisms of statins and the mechanisms underlying the protection against MPT and cell death by the compounds l-carnitine and piracetam. © 2013 Elsevier B.V. All rights reserved.7011/Mar8286Barazzoni, R., Zanetti, M., Cappellari, G.G., Semolic, A., Boschelle, M., Codarin, E., Pirulli, A., Guarnieri, G., Fatty acids acutely enhance insulin-induced oxidative stress and cause insulin resistance by increasing mitochondrial reactive oxygen species (ROS) generation and nuclear factor-kappaB inhibitor (IkappaB)-nuclear factor-kappaB (NFkappaB) activation in rat muscle, in the absence of mitochondrial dysfunction (2012) Diabetologia, 55, pp. 773-782Bhuiyan, J., Seccombe, D.W., The effects of 3-hydroxy-3-methylglutaryl-CoA reductase inhibition on tissue levels of carnitine and carnitine acyltransferase activity in the rabbit (1996) Lipids, 31, pp. 867-870Binienda, Z., Przybyla-Zawislak, B., Virmani, A., Schmued, L., L-Carnitine and neuroprotection in the animal model of mitochondrial dysfunction (2005) Ann. NY Acad. Sci., 1053, pp. 174-182Binienda, Z.K., Neuroprotective effects of l-carnitine in induced mitochondrial dysfunction (2003) Ann. NY Acad. Sci., 993 (289-295), pp. 289-345. , (discussion)Brill II, L.B., Bennett Jr., J.P., Dependence on electron transport chain function and intracellular signaling of genomic responses in SH-SY5Y cells to the mitochondrial neurotoxin MPP(+) (2003) Exp. Neurol., 181, pp. 25-38Campos, C.B., Degasperi, G.R., Pacifico, D.S., Alberici, L.C., Carreira, R.S., Guimaraes, F., Castilho, R.F., Vercesi, A.E., Ibuprofen-induced Walker 256 tumor cell death: Cytochrome c release from functional mitochondria and enhancement by calcineurin inhibition (2004) Biochem. Pharmacol., 68, pp. 2197-2206Castilho, R.F., Kowaltowski, A.J., Meinicke, A.R., Vercesi, A.E., Oxidative damage of mitochondria induced by Fe(II)citrate or t-butyl hydroperoxide in the presence of Ca2+: Effect of coenzyme Q redox state (1995) Free Radical Biol. Med., 18, pp. 55-59Collins, R., Armitage, J., Parish, S., Sleigh, P., Peto, R., MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: A randomised placebo-controlled trial (2003) Lancet, 361, pp. 2005-2016Cook, G.A., Khan, B., Heimberg, M., Feeding of lovastatin to rats increases the activity of the hepatic mitochondrial outer carnitine palmitoyltransferase (1988) Biochem. Biophys. Res. Commun., 150, pp. 1077-1082Elinos-Calderon, D., Robledo-Arratia, Y., Perez-De La Cruz, V., Pedraza-Chaverri, J., Ali, S.F., Santamaria, A., Early nerve ending rescue from oxidative damage and energy failure by L: -carnitine as post-treatment in two neurotoxic models in rat: Recovery of antioxidant and reductive capacities (2009) Exp. Brain Res., 197, pp. 287-296Endo, A., The discovery and development of HMG-CoA reductase inhibitors (1992) J. Lipid Res., 33, pp. 1569-1582Fagian, M.M., Pereira-Da-Silva, L., Martins, I.S., Vercesi, A.E., Membrane protein thiol cross-linking associated with the permeabilization of the inner mitochondrial membrane by Ca2+ plus prooxidants (1990) J. Biol. Chem., 265, pp. 19955-19960Figueira, T.R., Barros, M.H., Camargo, A.A., Castilho, R.F., Ferreira, J.C., Kowaltowski, A.J., Sluse, F.E., Vercesi, A.E., Mitochondria as a source of reactiveoxygen and nitrogen species: From molecular mechanisms to human health Antioxid. Redox. Signal, , http://dx.doi.org/10.1089/ars.2012.4729, in pressFigueira, T.R., Melo, D.R., Vercesi, A.E., Castilho, R.F., Safranine as a fluorescent probe for the evaluation of mitochondrial membrane potential in isolated organelles and permeabilized cells (2012) Methods Mol. Biol., 810, pp. 103-117Ghavami, S., Yeganeh, B., Stelmack, G.L., Kashani, H.H., Sharma, P., Cunnington, R., Rattan, S., Halayko, A.J., Apoptosis, autophagy and ER stress in mevalonate cascade inhibition-induced cell death of human atrial fibroblasts (2012) Cell Death Dis., 3, p. 330Ghosh, S., Kewalramani, G., Yuen, G., Pulinilkunnil, T., An, D., Innis, S.M., Allard, M.F., Rodrigues, B., Induction of mitochondrial nitrative damage and cardiac dysfunction by chronic provision of dietary omega-6 polyunsaturated fatty acids (2006) Free Radical Biol. Med., 41, pp. 1413-1424Grijalba, M.T., Vercesi, A.E., Schreier, S., Ca2+-induced increased lipid packing and domain formation in submitochondrial particles. A possible early step in the mechanism of Ca 2+-stimulated generation of reactive oxygen species by the respiratory chain (1999) Biochemistry, 38, pp. 13279-13287Gulcin, I., Antioxidant and antiradical activities of l-carnitine (2006) Life Sci., 78, pp. 803-811Guzman, M., Cortes, J.P., Castro, J., Effects of lovastatin on hepatic fatty acid metabolism (1993) Lipids, 28, pp. 1087-1093Hsu, M., Muchova, L., Morioka, I., Wong, R.J., Schroder, H., Stevenson, D.K., Tissue-specific effects of statins on the expression of heme oxygenase-1 in vivo (2006) Biochem. Biophys. Res. Commun., 343, pp. 738-744Hunter, D.R., Haworth, R.A., Southard, J.H., Relationship between configuration, function, and permeability in calcium-treated mitochondria (1976) J. Biol. Chem., 251, pp. 5069-5077Jun, D.W., Cho, W.K., Jun, J.H., Kwon, H.J., Jang, K.S., Kim, H.J., Jeon, H.J., Lee, M.H., Prevention of free fatty acid-induced hepatic lipotoxicity by carnitine via reversal of mitochondrial dysfunction (2011) Liver Int., 31, pp. 1315-1324Kaufmann, P., Torok, M., Zahno, A., Waldhauser, K.M., Brecht, K., Krahenbuhl, S., Toxicity of statins on rat skeletal muscle mitochondria (2006) Cell Mol. Life Sci., 63, pp. 2415-2425Keil, U., Scherping, I., Hauptmann, S., Schuessel, K., Eckert, A., Muller, W.E., Piracetam improves mitochondrial dysfunction following oxidative stress (2006) Br. J. Pharmacol., 147, pp. 199-208Kim, J.S., Wang, J.H., Lemasters, J.J., Mitochondrial permeability transition in rat hepatocytes after anoxia/reoxygenation: Role of Ca2+-dependent mitochondrial formation of reactive oxygen species (2012) Am. J. Physiol. Gastrointest. Liver Physiol., 302, pp. 723-G731Kowaltowski, A.J., Castilho, R.F., Vercesi, A.E., Mitochondrial permeability transition and oxidative stress (2001) FEBS Lett., 495, pp. 12-15Kwak, H.B., Thalacker-Mercer, A., Anderson, E.J., Lin, C.T., Kane, D.A., Lee, N.S., Cortright, R.N., Neufer, P.D., Simvastatin impairs ADP-stimulated respiration and increases mitochondrial oxidative stress in primary human skeletal myotubes (2012) Free Radical Biol. Med., 52, pp. 198-207Lemasters, J.J., Theruvath, T.P., Zhong, Z., Nieminen, A.L., Mitochondrial calcium and the permeability transition in cell death (2009) Biochim. Biophys. Acta, 1787, pp. 1395-1401Li, J., Sun, Y.M., Wang, L.F., Li, Z.Q., Pan, W., Cao, H.Y., Comparison of effects of simvastatin versus atorvastatin on oxidative stress in patients with coronary heart disease (2010) Clin. Cardiol., 33, pp. 222-227Madesh, M., Balasubramanian, K.A., Activation of liver mitochondrial phospholipase A2 by superoxide (1997) Arch. Biochem. Biophys., 346, pp. 187-192Manfredini, V., Biancini, G.B., Vanzin, C.S., Dal Vesco, A.M., Cipriani, F., Biasi, L., Tremea, R., Vargas, C.R., Simvastatin treatment prevents oxidative damage to DNA in whole blood leukocytes of dyslipidemic type 2diabetic patients (2010) Cell Biochem. Funct., 28, pp. 360-366Marcella, S.W., David, A., Ohman-Strickland, P.A., Carson, J., Rhoads, G.G., Statin use and fatal prostate cancer: A matched case-control study (2011) Cancer, 118, pp. 4046-4052Mondul, A.M., Weinstein, S.J., Virtamo, J., Albanes, D., Serum total and HDL cholesterol and risk of prostate cancer (2011) Cancer Causes Control, 22, pp. 1545-1552Moretti, S., Famularo, G., Marcellini, S., Boschini, A., Santini, G., Trinchieri, V., Lucci, L., De Simone, C., L-Carnitine reduces lymphocyte apoptosis and oxidant stress in HIV-1-infected subjects treated with zidovudine and didanosine (2002) Antioxid. Redox. Signal, 4, pp. 391-403Nishimura, M., Okimura, Y., Fujita, H., Yano, H., Lee, J., Suzaki, E., Inoue, M., Sasaki, J., Mechanism of 3-nitropropionic acid-induced membrane permeability transition of isolated mitochondria and its suppression by l-carnitine (2008) Cell Biochem. Funct., 26, pp. 881-891Oliveira, K.A., Zecchin, K.G., Alberici, L.C., Castilho, R.F., Vercesi, A.E., Simvastatin inducing PC3 prostate cancer cell necrosis mediated by calcineurin and mitochondrial dysfunction (2008) J. Bioenerg. Biomembr., 40, pp. 307-314Panov, A., Dikalov, S., Shalbuyeva, N., Taylor, G., Sherer, T., Greenamyre, J.T., Rotenone model of Parkinson disease: Multiple brain mitochondria dysfunctions after short term systemic rotenone intoxication (2005) J. Biol. Chem., 280, pp. 42026-42035Payne, C.M., Weber, C., Crowley-Skillicorn, C., Dvorak, K., Bernstein, H., Bernstein, C., Holubec, H., Garewal, H., Deoxycholate induces mitochondrial oxidative stress and activates NF-kappaB through multiple mechanisms in HCT-116 colon epithelial cells (2007) Carcinogenesis, 28, pp. 215-222Rasola, A., Sciacovelli, M., Pantic, B., Bernardi, P., Signal transduction to the permeability transition pore (2010) FEBS Lett, 584, pp. 1989-1996Ricchelli, F., Barbato, P., Milani, M., Gobbo, S., Salet, C., Moreno, G., Photodynamic action of porphyrin on Ca2+ influx in endoplasmic reticulum: A comparison with mitochondria (1999) Biochem. J., 338 (PART 1), pp. 221-227Ruiz-Ramirez, A., Chavez-Salgado, M., Peneda-Flores, J.A., Zapata, E., Masso, F., El-Hafidi, M., High-sucrose diet increases ROS generation, FFA accumulation, UCP2 level, and proton leak in liver mitochondria (2011) Am. J. Physiol. Endocrinol. Metab., 301, pp. 1198-E1207Sener, G., Paskaloglu, K., Satiroglu, H., Alican, I., Kacmaz, A., Sakarcan, A., L-Carnitine ameliorates oxidative damage due to chronic renal failure in rats (2004) J. Cardiovasc. Pharmacol., 43, pp. 698-705Shen, W., Liu, K., Tian, C., Yang, L., Li, X., Ren, J., Packer, L., Liu, J., Protective effects of R-alpha-lipoic acid and acetyl-l-carnitine in MIN6 and isolated rat islet cells chronically exposed to oleic acid (2008) J. Cell Biochem., 104, pp. 1232-1243Shepherd, J., Cobbe, S.M., Ford, I., Isles, C.G., Lorimer, A.R., Macfarlane, P.W., McKillop, J.H., Packard, C.J., Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group (1995) N. Engl. J. Med., 333, pp. 1301-1307Silva-Adaya, D., Perez-De La Cruz, V., Herrera-Mundo, M.N., Mendoza-Macedo, K., Villeda-Hernandez, J., Binienda, Z., Ali, S.F., Santamaria, A., Excitotoxic damage, disrupted energy metabolism, and oxidative stress in the rat brain: Antioxidant and neuroprotective effects of l-carnitine (2008) J. Neurochem., 105, pp. 677-689Sirvent, P., Mercier, J., Vassort, G., Lacampagne, A., Simvastatin triggers mitochondria-induced Ca2+ signaling alteration in skeletal muscle (2005) Biochem. Biophys. Res. Commun., 329, pp. 1067-1075Solesio, M.E., Saez-Atienzar, S., Jordan, J., Galindo, M.F., Nitropropionioc acid induces autophagy by mitochondrial permeability transition pore formation rather than activation of the mitochondrial fission pathway (2012) Br. J. Pharmacol.Toman, J., Fiskum, G., Influence of aging on membrane permeability transition in brain mitochondria (2011) J. Bioenerg. Biomembr., 43, pp. 3-10Tonin, A.M., Grings, M., Busanello, E.N., Moura, A.P., Ferreira, G.C., Viegas, C.M., Fernandes, C.G., Wajner, M., Long-chain 3-hydroxy fatty acids accumulating in LCHAD and MTP deficiencies induce oxidative stress in rat brain (2010) Neurochem. Int., 56, pp. 930-936Vamos, E., Voros, K., Vecsei, L., Klivenyi, P., Neuroprotective effects of l-carnitine in a transgenic animal model of Huntington's disease (2010) Biomed. Pharmacother., 64, pp. 282-286Vaseva, A.V., Marchenko, N.D., Ji, K., Tsirka, S.E., Holzmann, S., Moll, U.M., P53 opens the mitochondrial permeability transition pore to trigger Necrosis (2012) Cell, 149, pp. 1536-1548Vercesi, A.E., Dissociation of NAD(P)+-stimulated mitochondrial Ca2+ efflux from swelling and membrane damage (1984) Arch. Biochem. Biophys., 232, pp. 86-91Virmani, A., Gaetani, F., Binienda, Z., Effects of metabolic modifiers such as carnitines, coenzyme Q10, and PUFAs against different forms of neurotoxic insults: Metabolic inhibitors, MPTP, and methamphetamine (2005) Ann. NY Acad. Sci., 1053, pp. 183-191Virmani, A., Gaetani, F., Binienda, Z., Xu, A., Duhart, H., Ali, S.F., Role of mitochondrial dysfunction in neurotoxicity of MPP+: Partial protection of PC12 cells by acetyl-l-carnitine (2004) Ann. NY Acad. Sci., 1025, pp. 267-273Virmani, A., Gaetani, F., Imam, S., Binienda, Z., Ali, S., The protective role of l-carnitine against neurotoxicity evoked by drug of abuse, methamphetamine, could be related to mitochondrial dysfunction (2002) Ann. NY Acad. Sci., 965, pp. 225-232Virmani, A., Gaetani, F., Imam, S., Binienda, Z., Ali, S., Possible mechanism for the neuroprotective effects of l-carnitine on methamphetamine-evoked neurotoxicity (2003) Ann. NY Acad. Sci., 993 (197-207), pp. 198-287. , (Discussion)Yao, D., Shi, W., Gou, Y., Zhou, X., Yee, T., Zhou, Y., Liu, Z., Fatty acid-mediated intracellular iron translocation: A synergistic mechanism of oxidative injury (2005) Free Radical Biol. Med., 39, pp. 1385-1398Yapar, K., Kart, A., Karapehlivan, M., Atakisi, O., Tunca, R., Erginsoy, S., Citil, M., Hepatoprotective effect of l-carnitine against acute acetaminophen toxicity in mice (2007) Exp. Toxicol. Pathol., 59, pp. 121-128Ye, J., Li, J., Yu, Y., Wei, Q., Deng, W., Yu, L., L-Carnitine attenuates oxidant injury in HK-2 cells via ROS-mitochondria pathway (2010) Regul. Pept., 161, pp. 58-66Zhang, H., Jia, H., Liu, J., Ao, N., Yan, B., Shen, W., Wang, X., Luo, C., Combined R-alpha-lipoic acid and acetyl-l-carnitine exerts efficient preventative effects in a cellular model of Parkinson's disease (2010) J. Cell Mol. Med., 14, pp. 215-225Zhou, H., Liu, X., Liu, L., Yang, Z., Zhang, S., Tang, M., Tang, Y., Hu, R., Oxidative stress and apoptosis of human brain microvascular endothelial cells induced by free fatty acids (2009) J. Int. Med. Res., 37, pp. 1897-190

    Manganese-Induced Neurotoxicity through Impairment of Cross-Talk Pathways in Human Neuroblastoma Cell Line SH-SY5Y Differentiated with Retinoic Acid

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    Manganese (Mn) is an important element; yet acute and/or chronic exposure to this metal has been linked to neurotoxicity and neurodegenerative illnesses such as Parkinson’s disease and others via an unknown mechanism. To better understand it, we exposed a human neuroblastoma cell model (SH-SY5Y) to two Mn chemical species, MnCl(2) and Citrate of Mn(II) (0–2000 µM), followed by a cell viability assay, transcriptomics, and bioinformatics. Even though these cells have been chemically and genetically modified, which may limit the significance of our findings, we discovered that by using RA-differentiated cells instead of undifferentiated SH-SY5Y cell line, both chemical species induce a similar toxicity, potentially governed by disruption of protein metabolism, with some differences. The MnCl(2) altered amino acid metabolism, which affects RNA metabolism and protein synthesis. Citrate of Mn(II), however, inhibited the E3 ubiquitin ligases–target protein degradation pathway, which can lead to the buildup of damaged/unfolded proteins, consistent with histone modification. Finally, we discovered that Mn(II)-induced cytotoxicity in RA-SH-SY5Y cells shared 84 percent of the pathways involved in neurodegenerative diseases
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