Astaxanteno procedente de cangrejo (Procambarus clarkii) como ingrediente colorante en la alimentación de gallinas ponedoras

Chicken egg yolks generally owe their color to yellow carotenoids. The addition of synthetic red pigments allows changes in color, from the original yellow to red hues which may be more appealing to consumers in certain markets.Our aim has been to test whether ground crayfish shells, which are a rich and natural source of astaxanthin, produce detectable changes in the coloration of egg yolks through the accumulation of this carotenoid. Laying hens were fed with a commercial feed mixed with crayfish powder and the carotenoid profiles of the yolks in the eggs laid during the trial were monitored by HPLC. The analyses showed a progressive increase in the astaxanthin concentration in the egg yolks, reaching similar levels to those obtained for the rest of present carotenoid pigments.La yema de huevo de gallina debe su coloración a la presencia de carotenoides de tonalidad amarilla. La adición de colorantes sintéticos de tonalidades rojas permite modificar e incrementar la coloración de la yema desde el amarillo original a tonos rojos que pueden ser demandados en ciertos mercados según las preferencias del consumidor. El objetivo del trabajo fue probar si un triturado obtenido a partir de caparazones de cangrejo, que es una fuente natural y rica en astaxanteno, produce cambios detectables en la coloración de la yema de huevo por la acumulación de dicho carotenoide. Las gallinas ponedoras se alimentaron con un pienso comercial al que se adicionó triturado de caparazón de cangrejo. Se realizó un seguimiento de los cambios en la composición carotenoide (mediante HPLC) de la yema de los huevos puestos durante el periodo de alimentación suplementada. Los análisis mostraron una progresiva incorporación de astaxanteno que alcanzó niveles similares al resto de carotenoides presentes inicialmente en la yema

Secondary CoQ10 deficiency, bioenergetics unbalance in disease and aging

Coenzyme Q10 (CoQ10) deficiency is a rare disease characterized by a decreased accumulation of CoQ10 in cell membranes. Considering that CoQ10 synthesis and most of its functions are carried out in mitochondria, CoQ10 deficiency cases are usually considered a mitochondrial disease. A relevant feature of CoQ10 deficiency is that it is the only mitochondrial disease with a successful therapy available, the CoQ10 supplementation. Defects in components of the synthesis machinery caused by mutations in COQ genes generate the primary deficiency of CoQ10. Mutations in genes that are not directly related to the synthesis machinery cause secondary deficiency. Cases of CoQ10 deficiency without genetic origin are also considered a secondary deficiency. Both types of deficiency can lead to similar clinical manifestations, but the knowledge about primary deficiency is deeper than secondary. However, secondary deficiency cases may be underestimated since many of their clinical manifestations are shared with other pathologies. This review shows the current state of secondary CoQ10 deficiency, which could be even more relevant than primary deficiency for clinical activity. The analysis covers the fundamental features of CoQ10 deficiency, which are necessary to understand the biological and clinical differences between primary and secondary CoQ10 deficiencies. Further, a more in-depth analysis of CoQ10 secondary deficiency was undertaken to consider its origins, introduce a new way of classification, and include aging as a form of secondary deficiency.Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía, Grant/Award Numbers: UPO-1259581, UPO-126247, UPO-1265673; Instituto de Salud Carlos III, Grant/Award Number: PI17/01286; Ministerio de Educación, Cultura y Deporte, Grant/Award Numbers: FPU14/04873, FPU16/0326

Regulation of synthesis of coenzyme Q10

The regulation of gene expression needs many mechanisms of control which are multiple and diverse, encompassing from DNA structure to synthesis, modification and location of proteins. These processes, in addition to being tissue-specific, change during embryonic development and throughout the life of the organism. CoQ10 is essential to maintain cell homeostasis and to increase life-span. CoQ10 biosynthesis pathway is strictly regulated and this program involves different levels of regulation (transcriptional, post-transcriptional and post-translational). Here we have focused on processes of post-transcriptional regulation governed by RNA-binding proteins (RBPs) and review the role of these RBPs in senescence and aging. Finally, we report post-transcriptional and post-translational events involved in the regulation of several COQs genes involved in the CoQ10 synthesis complex assembly. The knowledge of processes that control CoQ10 levels in cells is key to develop therapies to stimulate the endogenous synthesis of CoQ10

Astaxanteno procedente de cangrejo (Procambarus clarkii) como ingrediente colorante en la alimentación de gallinas ponedoras

7 pages, 4 figures, 3 tables.[EN] Chicken egg yolks generally owe their color to yellow carotenoids. The addition of synthetic red pigments allows changes in color, from the original yellow to red hues which may be more appealing to consumers in certain markets.Our aim has been to test whether ground crayfish shells, which are a rich and natural source of astaxanthin, produce detectable changes in the coloration of egg yolks through the accumulation of this carotenoid. Laying hens were fed with a commercial feed mixed with crayfish powder and the carotenoid profiles of the yolks in the eggs laid during the trial were monitored by HPLC. The analyses showed a progressive increase in the astaxanthin concentration in the egg yolks, reaching similar levels to those obtained for the rest of present carotenoid pigments.[ES] La yema de huevo de gallina debe su coloración a la presencia de carotenoides de tonalidad amarilla. La adición de colorantes sintéticos de tonalidades rojas permite modificar e incrementar la coloración de la yema desde el amarillo original a tonos rojos que pueden ser demandados en ciertos mercados según las preferencias del consumidor. El objetivo del trabajo fue probar si un triturado obtenido a partir de caparazones de cangrejo, que es una fuente natural y rica en astaxanteno, produce cambios detectables en la coloración de la yema de huevo por la acumulación de dicho carotenoide. Las gallinas ponedoras se alimentaron con un pienso comercial al que se adicionó triturado de caparazón de cangrejo. Se realizó un seguimiento de los cambios en la composición carotenoide (mediante HPLC) de la yema de los huevos puestos durante el periodo de alimentación suplementada. Los análisis mostraron una progresiva incorporación de astaxanteno que alcanzó niveles similares al resto de carotenoides presentes inicialmente en la yema.Peer reviewe

Coenzyme Q biosynthesis is regulated by RNA-protein interaction

Resumen del póster presentado al 22nd IUBMB & 37th FEBS Congress, celebrado en Sevilla (España) del 4 al 9 de septiembre de 2012.-- et al.Coenzyme Q (CoQ) deficiency is a rare disorder with a variable phenotypic presentation that includes pure myopathy, myopathy with encephalopathy, cerebellar atrophy with ataxia, and infantile multisystem disease including encephalopathy and nephrophaty, and nephritic syndrome. Primary CoQ deficiency arises from mutations in COQ genes, while secondary forms of CoQ deficiency are caused by mutations in genes not involved in CoQ biosynthesis. In most patients, the exact site and nature of the defects on biosynthesis have not yet been identified. Because CoQ biosynthesis is complex and not fully defined, identification of the molecular genetic defects has been challenging. At least ten genes (COQ1-COQ10) forming a multi-peptide complex are required for CoQ biosynthesis. One of them, COQ7, is a central regulator of the pathway. We have previously demonstrated that NF-kB regulatesCOQ7 gene transcription under oxidative stress. Our current studies have uncovered the interaction of the RNAbinding protein (RBP) HuR and other as-yet unidentified RBPs with the 3'UTR region of the COQ7 mRNA. We propose a model of post-transcriptional regulation of COQ7 expression, whereby RBPs binding to the COQ7 3'UTR can rapidly and effectively alter COQ7 expression levels to adapt to changing cellular needs for cellular CoQ activity.Peer reviewe

ADCK2 deficiency reduces weight gain and increases body temperature of mice in high fat diet

Póster presentado al Joint Congress of the Spanish Societies of Genetics, Cell Biology and Developmental Biology, celebrado en Gijón del 24 al 27 de octubre de 2017.Primary coenzyme Q (CoQ) deficiency causes a heterogenic group of mitochondrial diseases with high variability in severity and tissues affectation. It has been identified that ADCK2 gene is involved in CoQ biosynthesis and its mutation is responsible of a mitochondrial myopathy and liver dysfunction in humans. ADCK2 knockout mice in heterozygosis developed a skeletal muscle mitochondrial dysfunction and myopathy, liver steatosis and defects in oxidation of fatty acids under standard diet (ST). To understand the role of lipids in its phenotype, we have studied the consequences of a high fat diet (HFD) in ADCK2 knockout mice. Wild type (WT) or ADCK2 knockout were assigned to either ST or HFD for seven months (WT-ST n=5, WTHFD n=6, +/- ADCK2-ST n=4, +/- ADCK2-HFD n=4) and weights were obtained. Animals were housed individually to control weekly food ingestion. Ratio kilocalories ingested per gram of body mass (BM) was determined. Rectal body temperature was explored. Strength and running performance were investigated. Western blots and RT-PCR were performed. Descriptive statics and one-way ANOVA analyses were used. WT animals presented a higher weight than mutants after 31 weeks of study (WT: 31.16g vs. ADCK2 KO: 27.55g in ST and WT: 43.47g vs. ADCK2 KO: 35.20g in HFD; p<0.05). Weight gain significantly differed between the genotype and diets (WT: 2.00g vs. ADCK2: 2.50g in ST and WT: 14.43g vs. ADCK2: 9.55g in HFD; p<0.05). There were no significant differences in kilocalorie intake among mice in the same diet independently of their genotype. Mutants in HFD presented a higher ratio kilocalorie ingested per gram of BM (p<0.05), they tend to exhibit higher body temperature. This group showed higher levels of mRNA and protein of UCP1 in brown adipose tissue, UCP2 in liver and UCP3 in quadriceps, proteins involved in dissipation of energy as heat. ADCK2 KO showed significantly higher insulin resistance on HFD (p<0.05) than control, and also showed decreased strength and running performance. MEFs from ADCK2 KO mice showed dysfunctional respiration by fatty acids as bioenergetics substrate. ADCK2 KO showed a defective fat accumulation under HFD due to decreased weight gain associated to higher rectal temperature, which is apparently due to upregulation of UCPs proteins. These results support the role of ADCK2 encoded protein in mitochondria oxidation of fatty acids and lipid metabolism. As skeletal muscle functions highly depend on fatty acids, our results support the decrease of strength and running performance of ADCK2 KO in HFD.Peer reviewe

Cellular Models for Primary CoQ Deficiency Pathogenesis Study

This work was supported by Junta de Andalucia grants P18-RT-4572, UPO-126247, UPO1265673 and BIO-177, the Instituto de Salud Carlos III FIS grant FIS PI20/00541, the FEDER Funding Pro-gram from the European Union, and CIBERER (U729)-ISCIII, and Spanish Ministry of Science, Innovation and Universities grant RED2018-102576-T.Primary coenzyme Q10 (CoQ) deficiency includes a heterogeneous group of mitochondrial diseases characterized by low mitochondrial levels of CoQ due to decreased endogenous biosynthesis rate. These diseases respond to CoQ treatment mainly at the early stages of the disease. The advances in the next generation sequencing (NGS) as whole-exome sequencing (WES) and whole-genome sequencing (WGS) have increased the discoveries of mutations in either gene already described to participate in CoQ biosynthesis or new genes also involved in this pathway. However, these technologies usually provide many mutations in genes whose pathogenic effect must be validated. To functionally validate the impact of gene variations in the disease’s onset and progression, different cell models are commonly used. We review here the use of yeast strains for functional complementation of human genes, dermal skin fibroblasts from patients as an excellent tool to demonstrate the biochemical and genetic mechanisms of these diseases and the development of human-induced pluripotent stem cells (hiPSCs) and iPSC-derived organoids for the study of the pathogenesis and treatment approaches.Junta de Andalucia P18-RT-4572 UPO-126247 UPO1265673 BIO-177Instituto de Salud Carlos III European Commission FIS PI20/00541FEDER Funding Pro-gram from the European Union Instituto de Salud Carlos III U729Spanish Ministry of Science, Innovation and Universities RED2018-102576-

The two faces of a same function: pro- and antiapoptotic role of ubiquinone

35 páginas, 7 figuras, 2 tablas. Scott R. Erlich (editor)Ubiquinone or coenzyme Q is an essential lipid present in almost all the cell membranes. It is a redox molecule able to accept and donate electrons to several other cellular components. This redox capability is key in the two main functions of ubiquinone in cells, an intermediate in the mitochondrial respiratory chain and the main lipidic antioxidant in cell membranes. During the last years, several works have confirmed the essential role of ubiquinone in life and death of cells. Several evidences indicate that ubiquinone is involved in cell defence against oxidative damage of membranes and particularly plasma membrane. Serum withdrawal increases lipid hydroperoxide levels resulting in a neutral sphingomyelinase-mediated apoptosis. Ubiquinone inhibits neutral sphingomyelinase activation preventing ceramide-dependen apoptosis. The cell population is based on the equilibrium between proliferation and cell death. The activation of cell growth factors leads to an increase of proliferation by activation of transduction signals, which activate/repress transcription factors involved on regulation of either anti- or pro-apoptotic genes. Multiple forms of tumor exhibit abnormal constitutive activation of phosphatidylinositol 3-kinase/Akt pathway, which is activated by several growth factors and constitutes a mechanism of tumor cells survival. Current evidence in our group support that biosynthesis of ubiquinone can be regulated by survival signal such as Akt or inhibitor kappa-B kinase path ways through of Nuclear Factor kappa-B and/or Forkhead Box Class O, a critical factor in the regulation of cell cycle arrest, apoptosis, and resistance to oxidate stress. Recent research has demonstrated that cells respond to chemotherapic agents by increasing ubiquinone levels, probably in an attempt of protect themselves from reactive oxygen species production. In addition, ubiquinone seems to be an important agent in the prevention of cell damage during aging as suggested by its increase in plasma membrane of caloric restricted animals. However, mitochondrial reduced and semireduced ubiquinone species are also a source of oxygen radicals that could promote molecular damage and apoptosis. Also, the insertion of foreign forms of ubiquinone to mitochondrial membranes induces higher levels of reactive oxygen species in cells and tissues. We show here a wide review of the two faces of a same function, the transfer of electrons by ubiquinone. Pro- and antiapoptotic cell mechanisms are dependent on this essential lipidic factor.Peer reviewe

Laboratory Diagnosis of a Case with Coenzyme Q10 Deficiency

Following an uneventful pregnancy, a boy was born from nonconsanguineous parents with no relevant family history. Within the first 24 hours after birth, he presented with cyanosis, lethargy, decreased spontaneous movements, hyperexcitability, and mild hypotonia. Under the suspicion of a mitochondrial disorder (MD), supplementation with different enzymatic cofactors was started, with no improvement. Refractory epilepsy, psychomotor delay, nystagmoid movements, and non-nephrotic range proteinuria were observed. The patient died at 9 months of age. Venous blood analysis showed lactic acidosis. Lactate was also increased in cerebrospinal fluid (CSF): 3.74 mmol/L (reference interval [RI]: 1.11–2.22 mmol/L)). Impaired mitochondrial metabolism was further suggested by an increase of plasma alanine (797 µmol/L, RI: 190–337 µmol/L), CSF alanine (81 µmol/L, RI: 12–52 µmol/L) and an abnormal urine organic acid profile (increased excretion of succinate, fumarate, and 2-oxoglutarate). Increased concentrations of fibroblast growth factor-21 (FGF-21) (952 ng/L, RI: 0–300 ng/L) were detected. Analysis of coenzyme Q10 (CoQ) by HPLC-electrochemical detection gave normal results in plasma, while a decrease in fibroblasts (36 nmol/g protein, RI: 91–151 nmol/g protein) and skeletal muscle was observed (56.2 nmol/g protein, RI: 110–480 nmol/g protein) (Fig. 1). The activity of mitochondrial respiratory chain (MRC) succinate-cytochrome c reductase in fibroblasts, which depends on CoQ status, was reduced (9.04 nmol/min/mg protein) when compared with a control line of neonatal fibroblasts analyzed in parallel (16.01 nmol/min/mg protein).This work was supported by grants from the Instituto de Salud Carlos III (ISCIII-FIS PI17/00109 and PI17/01286). A.J. Paredes-Fuentes, a grant from the Instituto de Salud Carlos III (FI18/00253)