Relevance of fatty acid oxidation in regulation of the outer mitochondrial membrane permeability for ADP

AbstractThe present study on saponin-treated rat heart muscle fibers has revealed a new function of the fatty acid oxidation system in the regulation of the outer mitochondrial membrane (OMM) permeability for ADP. It is found that oxidation of palmitoyl-CoA+carnitine, palmitoyl-L-carnitine and octanoyl-L-carnitine (alone or in combination with pyruvate+malate) dramatically decreased a very high value of apparent Km of oxidative phosphorylation for ADP. Octanoyl-D-carnitine, as well as palmitate, palmitoyl-CoA, and palmitoyl-L-carnitine were not effective in this respect, when their oxidation was prevented by the absence of necessary cofactors or blocked with rotenone. Our data suggest that oxidation, but not transport of fatty acids into mitochondria, induces an increase in the OMM permeability for ADP

What controls the outer mitochondrial membrane permeability for ADP: facts for and against the role of oncotic pressure

AbstractIn our study 10% of bovine serum albumin was added to the physiological incubation medium to mimic the oncotic pressure of the cellular cytoplasm and to test for its effect on the respiration of isolated rat heart mitochondria, saponin- or saponin plus crude collagenase (type IV)-treated heart muscle fibers and saponin-treated rat quadriceps muscle fibers. Pyruvate and malate were used as substrates. We found that albumin slightly decreased the maximal ADP-stimulated respiration rate only for saponin-treated heart muscle fibers. The apparent Km ADP of oxidative phosphorylation increased significantly, by 70–100%, for isolated heart mitochondria, saponin plus collagenase-treated heart muscle fibers and for saponin-treated quadriceps muscle fibers but remained unchanged for saponin-treated heart muscle fibers. The saponin-treated heart muscle fibers were characterized by a very high control apparent Km ADP value (234±24 μM ADP) compared with other preparations (14–28 μM ADP). The results suggest that in vivo the oncotic pressure is not the relevant factor causing the low outer mitochondrial membrane permeability for ADP in cardiomyocytes, in contrast to quadriceps muscle cells. It is likely that the outer mitochondrial membrane-bound protein(s) which is supposed to remain in saponin-treated heart muscle fibers is responsible for this property of the membrane

Evolution of a family of metazoan active-site-serine enzymes from penicillin-binding proteins: a novel facet of the bacterial legacy

<p>Abstract</p> <p>Background</p> <p>Bacterial penicillin-binding proteins and β-lactamases (PBP-βLs) constitute a large family of serine proteases that perform essential functions in the synthesis and maintenance of peptidoglycan. Intriguingly, genes encoding PBP-βL homologs occur in many metazoan genomes including humans. The emerging role of LACTB, a mammalian mitochondrial PBP-βL homolog, in metabolic signaling prompted us to investigate the evolutionary history of metazoan PBP-βL proteins.</p> <p>Results</p> <p>Metazoan PBP-βL homologs including LACTB share unique structural features with bacterial class B low molecular weight penicillin-binding proteins. The amino acid residues necessary for enzymatic activity in bacterial PBP-βL proteins, including the catalytic serine residue, are conserved in all metazoan homologs. Phylogenetic analysis indicated that metazoan PBP-βL homologs comprise four alloparalogus protein lineages that derive from α-proteobacteria.</p> <p>Conclusion</p> <p>While most components of the peptidoglycan synthesis machinery were dumped by early eukaryotes, a few PBP-βL proteins were conserved and are found in metazoans including humans. Metazoan PBP-βL homologs are active-site-serine enzymes that probably have distinct functions in the metabolic circuitry. We hypothesize that PBP-βL proteins in the early eukaryotic cell enabled the degradation of peptidoglycan from ingested bacteria, thereby maximizing the yield of nutrients and streamlining the cell for effective phagocytotic feeding.</p

Modification of permeability transition pore arginine(s) by phenylglyoxal derivatives in isolated mitochondria and mammalian cells. Structure-function relationship of arginine ligands.

Methylglyoxal and synthetic glyoxal derivatives react covalently with arginine residue(s) on the mitochondrial permeability transition pore (PTP). In this study, we have investigated how the binding of a panel of synthetic phenylglyoxal derivatives influences the opening and closing of the PTP. Using both isolated mitochondria and mammalian cells, we demonstrate that the resulting arginine-phenylglyoxal adduct can lead to either suppression or induction of permeability transition, depending on the net charge and hydrogen bonding capacity of the adduct. We report that phenylglyoxal derivatives that possess a net negative charge and/or are capable of forming hydrogen bonds induced permeability transition. Derivatives that were overall electroneutral and cannot form hydrogen bonds suppressed permeability transition. When mammalian cells were incubated with low concentrations of negatively charged phenylglyoxal derivatives, the addition of oligomycin caused a depolarization of the mitochondrial membrane potential. This depolarization was completely blocked by cyclosporin A, a PTP opening inhibitor, indicating that the depolarization was due to PTP opening. Collectively, these findings highlight that the target arginine(s) is functionally linked with the opening/closing mechanism of the PTP and that the electric charge and hydrogen bonding of the resulting arginine adduct influences the conformation of the PTP. These results are consistent with a model where the target arginine plays a role as a voltage sensor

Analysis of Morphological and Morphometric Changes in a Parenchymal Tissue after the Radiofrequency Ablation Procedure

Publisher Copyright: © 2023 by the authors.Background and Objectives: Prostate cancer is on the rise in the European Union, and radiofrequency ablation (RFA) is one of the minimally invasive treatment options used for its treatment. Therefore, the aim of this study was to investigate and analyze the effects of RFA on prostate tissues. Materials and Methods: A standard prostate RFA procedure was performed on 13 non-purebred dogs in three sessions: no cooling (NC), cooling with a 0.1% NaCl solution (C.01), and cooling using a 0.9% NaCl solution (C.09). Microtome-cut 2–3 µm sections of prostate samples were stained with hematoxylin and eosin and further examined. Results: A histopathologic evaluation identified four zones of exposure: direct, application, necrosis, and transitional, as the damage on tissues decreased going further from the ablation site. The areas and perimeters of these zones were calculated, and geometric shapes of ablative lesions were evaluated using the quotient formula. Areas and perimeters of prostate tissue lesions in the NC and C.09 sessions were of similar size, whereas those found in C.01 were statistically significantly smaller. Lesions observed in session C.01 were of the most regular geometric shape, while the most irregular ones were found in session C.09. The shapes of lesions closest to the ablation electrode were the most irregular, becoming more regular the further away from the electrode they were. Conclusions: Prostate RFA leads to tissue damage with distinct morphological zones. Notably, the prostate lesions were the smallest and the most regular in shape after RFA procedures using the 0.1% NaCl cooling solution. It can be argued that smaller ablation sites may result in smaller scars, thus allowing for faster tissue healing if the blood flow and innervation at the ablation site are not compromised.Peer reviewe

Phenotypic and Functional Heterogeneity of Monocyte Subsets in Chronic Heart Failure Patients

Chronic heart failure (CHF) results when the heart cannot consistently supply the body&rsquo;s tissues with oxygen and required nutrients. CHF can be categorized as heart failure (HF) with preserved ejection fraction (HFpEF) or HF with reduced ejection fraction (HFrEF). There are different causes and mechanisms underlying HF pathogenesis; however, inflammation can be regarded as one of the factors that promotes both HFrEF and HFpEF. Monocytes, a subgroup of leukocytes, are known to be cellular mediators in response to cardiovascular injury and are closely related to inflammatory reactions. These cells are a vital component of the immune system and are the source of macrophages, which participate in cardiac tissue repair after injury. However, these monocytes are not as homogenous as thought and can present different functions under different cardiovascular disease conditions. In addition, there is still an open question regarding whether the functions of monocytes and macrophages should be regarded as causes or consequences in CHF development. Therefore, the aim of this work was to summarize current studies on the functions of various monocyte subsets in CHF with a focus on the role of a certain monocyte subset in HFpEF and HFrEF patients, as well as the subsets&rsquo; relationship to inflammatory markers

Protecting the Heart Against Ischemia/Reperfusion-Induced Necrosis and Apoptosis: the Effect of Anthocyanins

Background and Objective. It is well known that cardiomyocyte apoptosis contributes to ischemic heart damage. There is also increasing evidence that the polyphenolic compounds of natural origin, such as anthocyanins, may attenuate ischemia/reperfusion injury though the mechanisms of such protection are not clear. Following our previous studies showing the effect of certain anthocyanins on cytochrome c redox state, mitochondrial functions, and ischemia-induced caspase activation in the heart, here we investigated whether these anthocyanins can rescue cardiac cells from death by the mechanism involving the reduction of cytosolic cytochrome c. Material and Methods. Before global ischemia and reperfusion, isolated rat hearts were preloaded with cyanidin-3-O-glucoside (Cy3G) that has high cytochrome c-reducing capacity or pelargonidin- 3-O-glucoside (Pg3G) that possesses low reducing activity. Cell death was evaluated assessing apoptosis by the TUNEL method or necrosis measuring the release of lactate dehydrogenase into perfusate. Results. The perfusion of hearts with 20-μM Cy3G prevented ischemia/reperfusion-induced apoptosis of cardiomyocytes: the number of TUNEL-positive myocytes was decreased by 73% if compared with the untreated ischemic group. The same effect was observed measuring the activity of lactate dehydrogenase as the measure of necrosis: perfusion with 20-μM Cy3G reduced the level of LDH release into the perfusate to the control level. The perfusion of hearts with 20-μM Pg3G did not prevent ischemia/reperfusion-induced apoptosis as well as necrosis. Conclusions. Cy3G protected the rat heart from ischemia/reperfusion-induced apoptosis and necrosis; meanwhile, Pg3G did not exert any protective effect. The protective effect of Cy3G may be related due to its high capacity to reduce cytosolic cytochrome c

KATP kanalų aktyvatorių poveikis širdies mitochondrijų membranų laidumui kalio jonams, protonams ir adp acidozės metu

The inhibition of ATP-ase or the impairment of ADP/ATP transport is suggested to be responsible for the cardioprotective effects of KATP channel openers. In this study, we investigated the ability of KATP channel openers to affect K+ and H+ flux to the matrix of rat heart mitochondria as well as permeability of mitochondrial membranes for ADP under mildly acidic (pH 6.8) conditions. K+ and H+ flux to the mitochondrial matrix was registered spectrophotometrically as the swelling of non-respiring mitochondria at 540 nm in the KNO3 and NH4NO3 medium. The apparent KM for ADP of mitochondria was estimated from the least-squares fit to the Michaelis–Menten equation. The results showed that the KATP channel openers diazoxide and pinacidil could activate potassium ion and proton flux to the mitochondrial matrix both under normal (pH 7.4) and mildly acidic (pH 6.8) conditions. Mild acidosis increased the apparent KM for ADP of mitochondria two times (up to 60.6 ± 3.4 mM) as compared to control (33.0 ± 3.2 mM). The KATP channel opener diazoxide (100 mM) increased the apparent KM for ADP by 40% under control and by 30% under mildly acidic conditions. Our results suggest that KATP channel openers could suppress the ADP/ATP exchange during ischemia and thus promote preservation of ATP in cardiomyocytes

Materialistic values impact on pro-environmental behavior: the case of transition country as Lithuania

Article no. 118859Materialism is becoming a global phenomenon and is increasing exponentially. Lithuania, which has survived a long period of occupation, experienced privatization and goods’ famine is attributed to the transition countries. In terms of materialistic values, Lithuania is not an exception, as material wealth and image are also very important. Thus, the main question of this paper was whether materialistic values could be reconciled with the pro-environmental behavior, which can be considered as one of the main aspects seeking sustainability. According to the Lithuanian representative survey and by applying the approach of structural equation modeling, the results showed that materialistic values had an insignificant impact on the environmental concern, belief, and responsibility. Meanwhile, analyzing the impact of materialistic values on conservation and princely behavior, it was found that because of gain goals, materialists were more linked to perform conservation behavior, and because of hedonistic goals – princely behavior. Moreover, the environmental concern significantly and positively influenced princely behavior, but negatively – conservation behavior. Environmental beliefs had a positive impact only on conservation behavior. These findings could be important seeking the promotion of pro-environmental behavior, particularly in materialistic societiesAplinkotyros katedraKauno medicinos universitetas. Biomedicininių tyrimų institutasVytauto Didžiojo universiteta