A new insight into the molecular hydrogen effect on coenzyme Q and mitochondrial function of rats

2020 ◽  
Vol 98 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Anna Gvozdjáková ◽  
Jarmila Kucharská ◽  
Branislav Kura ◽  
Ol’ga Vančová ◽  
Zuzana Rausová ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Phosphorylation ◽  
Respiratory Chain ◽  
Mitochondrial Function ◽  
Complex I ◽  
Molecular Hydrogen ◽  
Coenzyme Q ◽  
Complex Ii ◽  
Atp Production ◽  
Q Cycle

Mitochondria are the major source of cellular energy metabolism. In the cardiac cells, mitochondria produce by way of the oxidative phosphorylation more than 90% of the energy supply in the form of ATP, which is utilized in many ATP-dependent processes, like cycling of the contractile proteins or maintaining ion gradients. Reactive oxygen species (ROS) are by-products of cellular metabolism and their levels are controlled by intracellular antioxidant systems. Imbalance between ROS and the antioxidant defense leads to oxidative stress and oxidative changes to cellular biomolecules. Molecular hydrogen (H2) has been proved as beneficial in the prevention and therapy of various diseases including cardiovascular disorders. It selectively scavenges hydroxyl radical and peroxynitrite, reduces oxidative stress, and has anti-inflammatory and anti-apoptotic effects. The effect of H2 on the myocardial mitochondrial function and coenzyme Q levels is not well known. In this paper, we demonstrated that consumption of H2-rich water (HRW) resulted in stimulated rat cardiac mitochondrial electron respiratory chain function and increased levels of ATP production by Complex I and Complex II substrates. Similarly, coenzyme Q9 levels in the rat plasma, myocardial tissue, and mitochondria were increased and malondialdehyde level in plasma was reduced after HRW administration. Based on obtained data, we hypothesize a new metabolic pathway of the H2 effect in mitochondria on the Q-cycle and in mitochondrial respiratory chain function. The Q-cycle contains three coenzyme Q forms: coenzyme Q in oxidized form (ubiquinone), radical form (semiquinone), or reduced form (ubiquinol). H2 may be a donor of both electron and proton in the Q-cycle and thus we can suppose stimulation of coenzyme Q production. When ubiquinone is reduced to ubiquinol, lipid peroxidation is reduced. Increased CoQ9 concentration can stimulate electron transport from Complex I and Complex II to Complex III and increase ATP production via mitochondrial oxidative phosphorylation. Our results indicate that H2 may function to prevent/treat disease states with disrupted myocardial mitochondrial function.

scholarly journals Selective NADH communication from α-ketoglutarate dehydrogenase to mitochondrial transhydrogenase prevents reactive oxygen species formation under reducing conditions in the heart

2020 ◽  
Vol 115 (5) ◽  
Author(s):  
Michael Wagner ◽  
Edoardo Bertero ◽  
Alexander Nickel ◽  
Michael Kohlhaas ◽  
Gary E. Gibson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Respiratory Chain ◽  
Complex I ◽  
Krebs Cycle ◽  
Reactive Oxygen Species Formation ◽  
Atp Production ◽  
Reducing Conditions ◽  
Species Formation ◽  
Ketoglutarate Dehydrogenase

Abstract In heart failure, a functional block of complex I of the respiratory chain provokes superoxide generation, which is transformed to H2O2 by dismutation. The Krebs cycle produces NADH, which delivers electrons to complex I, and NADPH for H2O2 elimination via isocitrate dehydrogenase and nicotinamide nucleotide transhydrogenase (NNT). At high NADH levels, α-ketoglutarate dehydrogenase (α-KGDH) is a major source of superoxide in skeletal muscle mitochondria with low NNT activity. Here, we analyzed how α-KGDH and NNT control H2O2 emission in cardiac mitochondria. In cardiac mitochondria from NNT-competent BL/6N mice, H2O2 emission is equally low with pyruvate/malate (P/M) or α-ketoglutarate (α-KG) as substrates. Complex I inhibition with rotenone increases H2O2 emission from P/M, but not α-KG respiring mitochondria, which is potentiated by depleting H2O2-eliminating capacity. Conversely, in NNT-deficient BL/6J mitochondria, H2O2 emission is higher with α-KG than with P/M as substrate, and further potentiated by complex I blockade. Prior depletion of H2O2-eliminating capacity increases H2O2 emission from P/M, but not α-KG respiring mitochondria. In cardiac myocytes, downregulation of α-KGDH activity impaired dynamic mitochondrial redox adaptation during workload transitions, without increasing H2O2 emission. In conclusion, NADH from α-KGDH selectively shuttles to NNT for NADPH formation rather than to complex I of the respiratory chain for ATP production. Therefore, α-KGDH plays a key role for H2O2 elimination, but is not a relevant source of superoxide in heart. In heart failure, α-KGDH/NNT-dependent NADPH formation ameliorates oxidative stress imposed by complex I blockade. Downregulation of α-KGDH may, therefore, predispose to oxidative stress in heart failure.

Effect of hyperthermia and acidosis on equine skeletal muscle mitochondrial oxygen consumption

2020 ◽  
pp. 1-10
Author(s):  
M.S. Davis ◽  
M.R. Fulton ◽  
A. Popken
Keyword(s):  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Oxidative Phosphorylation ◽  
Muscle Fatigue ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Complex I ◽  
Mitochondrial Oxygen Consumption ◽  
Biochemical Basis ◽  
Complex Ii

The skeletal muscle of exercising horses develops pronounced hyperthermia and acidosis during strenuous or prolonged exercise, with very high tissue temperature and low pH associated with muscle fatigue or damage. The purpose of this study was to evaluate the individual effects of physiologically relevant hyperthermia and acidosis on equine skeletal muscle mitochondrial function, using ex vivo measurement of oxygen consumption to assess the function of different mitochondrial elements. Fresh triceps muscle biopsies from 6 healthy unfit Thoroughbred geldings were permeabilised to permit diffusion of small molecular weight substrates through the sarcolemma and analysed in a high resolution respirometer at 38, 40, 42, and 44 °C, and pH=7.1, 6.5, and 6.1. Oxygen consumption was measured under conditions of non-phosphorylating (leak) respiration and phosphorylating respiration through Complex I and Complex II. Data were analysed using a one-way repeated measures ANOVA and data are expressed as mean ± standard deviation. Leak respiration was ~3-fold higher at 44 °C compared to 38 °C regardless of electron source (Complex I: 22.88±3.05 vs 8.08±1.92 pmol O2/mg/s), P=0.002; Complex II: 79.14±23.72 vs 21.43±11.08 pmol O2/mg/s, P=0.022), resulting in a decrease in efficiency of oxidative phosphorylation. Acidosis had minimal effect on mitochondrial respiration at pH=6.5, but pH=6.1 resulted in a 50% decrease in mitochondrial oxygen consumption. These results suggest that skeletal muscle hyperthermia decreases the efficiency of oxidative phosphorylation through increased leak respiration, thus providing a specific biochemical basis for hyperthermia-induced muscle fatigue. The effect of myocellular acidosis on mitochondrial respiration was minimal under typical levels of acidosis, but atypically severe acidosis can lead to impairment of mitochondrial function.

scholarly journals Phytochemicals from the Cocoa Shell Modulate Mitochondrial Function, Lipid and Glucose Metabolism in Hepatocytes via Activation of FGF21/ERK, AKT, and mTOR Pathways

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 136
Author(s):  
Miguel Rebollo-Hernanz ◽  
Yolanda Aguilera ◽  
Maria A. Martin-Cabrejas ◽  
Elvira Gonzalez de Gonzalez de Mejia
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fatty Acid Synthase ◽  
Cell Model ◽  
Fibroblast Growth Factor 21 ◽  
Alcoholic Fatty Liver ◽  
Atp Production ◽  
Cocoa Shell

The cocoa shell is a by-product that may be revalorized as a source of bioactive compounds to prevent chronic cardiometabolic diseases. This study aimed to investigate the phytochemicals from the cocoa shell as targeted compounds for activating fibroblast growth factor 21 (FGF21) signaling and regulating non-alcoholic fatty liver disease (NAFLD)-related biomarkers linked to oxidative stress, mitochondrial function, and metabolism in hepatocytes. HepG2 cells treated with palmitic acid (PA, 500 µmol L−1) were used in an NAFLD cell model. Phytochemicals from the cocoa shell (50 µmol L−1) and an aqueous extract (CAE, 100 µg mL−1) enhanced ERK1/2 phosphorylation (1.7- to 3.3-fold) and FGF21 release (1.4- to 3.4-fold) via PPARα activation. Oxidative stress markers were reduced though Nrf-2 regulation. Mitochondrial function (mitochondrial respiration and ATP production) was protected by the PGC-1α pathway modulation. Cocoa shell phytochemicals reduced lipid accumulation (53–115%) and fatty acid synthase activity (59–93%) and prompted CPT-1 activity. Glucose uptake and glucokinase activity were enhanced, whereas glucose production and phosphoenolpyruvate carboxykinase activity were diminished. The increase in the phosphorylation of the insulin receptor, AKT, AMPKα, mTOR, and ERK1/2 conduced to the regulation of hepatic mitochondrial function and energy metabolism. For the first time, the cocoa shell phytochemicals are proved to modulate FGF21 signaling. Results demonstrate the in vitro preventive effect of the phytochemicals from the cocoa shell on NAFLD.

scholarly journals Gene by environmental interactions affecting oxidative phosphorylation and thermal sensitivity

2016 ◽  
Vol 311 (1) ◽  
pp. R157-R165 ◽  
Author(s):  
Tara Z. Baris ◽  
Pierre U. Blier ◽  
Nicolas Pichaud ◽  
Douglas L. Crawford ◽  
Marjorie F. Oleksiak
Keyword(s):  
Oxidative Phosphorylation ◽  
Complex I ◽  
Thermal Sensitivity ◽  
Single Species ◽  
Mitochondrial Haplotype ◽  
Acclimation Temperature ◽  
Atp Production ◽  
Acute Response ◽  
Relative Contribution ◽  
Mitochondrial Genotype

The oxidative phosphorylation (OxPhos) pathway is responsible for most aerobic ATP production and is the only metabolic pathway with proteins encoded by both nuclear and mitochondrial genomes. In studies examining mitonuclear interactions among distant populations within a species or across species, the interactions between these two genomes can affect metabolism, growth, and fitness, depending on the environment. However, there is little data on whether these interactions impact natural populations within a single species. In an admixed Fundulus heteroclitus population with northern and southern mitochondrial haplotypes, there are significant differences in allele frequencies associated with mitochondrial haplotype. In this study, we investigate how mitochondrial haplotype and any associated nuclear differences affect six OxPhos parameters within a population. The data demonstrate significant OxPhos functional differences between the two mitochondrial genotypes. These differences are most apparent when individuals are acclimated to high temperatures with the southern mitochondrial genotype having a large acute response and the northern mitochondrial genotype having little, if any acute response. Furthermore, acute temperature effects and the relative contribution of Complex I and II depend on acclimation temperature: when individuals are acclimated to 12°C, the relative contribution of Complex I increases with higher acute temperatures, whereas at 28°C acclimation, the relative contribution of Complex I is unaffected by acute temperature change. These data demonstrate a complex gene by environmental interaction affecting the OxPhos pathway.

Abstract 355: Effect of Poloxamer 188 on Rat Brain Isolated Mitochondria After Exposure to Hydrogen Peroxide

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Johannes A Pille ◽  
Michele M Salzman ◽  
Anna A Sonju ◽  
Felicia P Lotze ◽  
Josephine E Hees ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Oxygen Consumption ◽  
Mitochondrial Function ◽  
Complex I ◽  
Room Temperature ◽  
In Vitro Model ◽  
Atp Synthesis ◽  
Complex Ii ◽  
Vitro Model

Introduction: In a pig model of myocardial infarction (MI), intracoronary delivered Poloxamer (P) 188 significantly reduces ischemia/reperfusion (IR) injury when given immediately upon reperfusion, with improved mitochondrial function as a predominant effect. As mitochondria are heavily damaged during IR, a direct effect of P188 on mitochondria may lead to better therapy options during reperfusion. To show not only a similar reduction of IR injury by P188 in the brain, but also a direct P188 effect on mitochondria, we established an in-vitro model of IR that consists of damaging isolated rat brain mitochondria with hydrogen peroxide (H 2 O 2 ), one component of ischemia, then applying P188, and analyzing mitochondrial function. Methods: Male Sprague-Dawley rat brains were removed, and the mitochondria isolated by differential centrifugation and Percoll gradients, then kept on ice to slow their bioenergetics prior to any experimental treatments. Mitochondria were exposed to 200 μM H 2 O 2 for 10 min at room temperature with slight agitation; controls received no H 2 O 2 . Samples were then diluted ½ with buffer ± P188 (250 μM after dilution) to simulate reperfusion and treatment, and kept at room temperature for 10 further minutes. ATP synthesis was measured in a luminometer using a luciferase enzymatic assay. Oxygen consumption was measured by closed cell respirometry with an oxygen meter. In both assays, Complex I and Complex II were examined; Complex I substrates glutamate and malate, Complex II substrate succinate plus the Complex I inhibitor rotenone. Statistics: Data are expressed as mean ± SEM. One-Way ANOVA, SNK-Test; Kruskal-Wallis-Test; α=0.05, * vs control. Results: In both Complex I and II, mitochondrial function was significantly impaired by H 2 O 2 , with ATP synthesis affected more at Complex I and oxygen consumption affected more at Complex II. Addition of P188 did not provide any significant improvement in mitochondrial function. Conclusions: Although P188 significantly reduced IR injury when given during reperfusion in a pig model of MI, it does not appear to provide direct protection to mitochondria in this in-vitro model. Whether the exposure to H 2 O 2 causes the appropriate injury for P188 to become effective remains to be elucidated.

Abstract 323: Dronedarone Impairs Cardiac Mitochondrial Oxidative Phosphorylation in Dose-Dependent Manner

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Larisa Emelyanova ◽  
Sirisha Gudlawar ◽  
Farhan Rizvi ◽  
Ekhson Holmuhamedov ◽  
Monika Thakur ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Complex I ◽  
Consumption Rate ◽  
Inhibitory Effect ◽  
Left Ventricular ◽  
Dependent Manner ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Complex Ii ◽  
Dose Dependent ◽  
Energetic Reserves

Introduction: Dronedarone (DR), a new antiarrhythmic drug, was recently shown to worsen heart failure (HF) and mortality in patients with atrial fibrillation and left ventricular dysfunction. However, the mechanism underlying the adverse effect is not known. Since, myocardium depends on mitochondrial oxidative phosphorylation (OXPHOS), we hypothesized that DR impairs mitochondrial function, which could further compropmise energetic reserves predisposing to worsening of HF and death in patients with HF. Methods: Mitochondria isolated from rat heart (2 month old, SD) were treated with DR (1, 5, 10, 20, 50 μM), and the effect on oxygen consumption rate (OCR) in State 3 (St 3, ADP stimulated), State 4 (St 4o, oligomycin) and following FCCP addition were determined using Seahorse XF24 Analyzer in the presence of glutamate/malate (complex I substrates) and succinate/rotenone (complex II substrate). Results: DR dose dependently reduced St 3 respiration both in the presence of complex I (Fig). In the presence of glutamate/malate, DR inhibited OCR by 16%, 20%, 25%, 39% and 100% at 1, 5, 10, 20, 50 μM, respectively, when compared to untreated control. At 20 μM, DR uncoupled mitochondria and increased St 4o respiration. DR at 50 μM was toxic with complete inhibition of OCR and loss of membrane potential. Similar results were observed when succinate/rotenone were used to assess complex II activity. Conclusion: DR has dose-dependent inhibitory effect on mitochondrial respiration, inhibiting OXPHOS at low concentration (1-10 μM), uncoupling at higher (20 μM) and toxic effect at 50 μM. Impairment of mitochondrial energetics could explain DR results reported in HF patients in clinical trials.

scholarly journals Protein kinase C-α inhibits the repair of oxidative phosphorylation after S-(1,2-dichlorovinyl)-l-cysteine injury in renal cells

2004 ◽  
Vol 287 (1) ◽  
pp. F64-F73 ◽  
Author(s):  
Xiuli Liu ◽  
Malinda L. Godwin ◽  
Grażyna Nowak
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Oxidative Phosphorylation ◽  
Atpase Activity ◽  
Mitochondrial Function ◽  
Recovery Period ◽  
Β Subunit ◽  
Atp Production ◽  
Kinase C ◽  
Mitochondrial Functions

Previously, we showed that physiological functions of renal proximal tubular cells (RPTC) do not recover following S-(1,2-dichlorovinyl)-l-cysteine (DCVC)-induced injury. This study investigated the role of protein kinase C-α (PKC-α) in the lack of repair of mitochondrial function in DCVC-injured RPTC. After DCVC exposure, basal oxygen consumption (Qo2), uncoupled Qo2, oligomycin-sensitive Qo2, F1F0-ATPase activity, and ATP production decreased, respectively, to 59, 27, 27, 57, and 68% of controls. None of these functions recovered. Mitochondrial transmembrane potential decreased 53% after DCVC injury but recovered on day 4. PKC-α was activated 4.3- and 2.5-fold on days 2 and 4, respectively, of the recovery period. Inhibition of PKC-α activation (10 nM Go6976) did not block DCVC-induced decreases in mitochondrial functions but promoted the recovery of uncoupled Qo2, oligomycin-sensitive Qo2, F1F0-ATPase activity, and ATP production. Protein levels of the catalytic β-subunit of F1F0-ATPase were not changed by DCVC or during the recovery period. Amino acid sequence analysis revealed that α-, β-, and ε-subunits of F1F0-ATPase have PKC consensus motifs. Recombinant PKC-α phosphorylated the β-subunit and decreased F1F0-ATPase activity in vitro. Serine but not threonine phosphorylation of the β-subunit was increased during late recovery following DCVC injury, and inhibition of PKC-α activation decreased this phosphorylation. We conclude that during RPTC recovery following DCVC injury, 1) PKC-α activation decreases F0F1-ATPase activity, oxidative phosphorylation, and ATP production; 2) PKC-α phosphorylates the β-subunit of F1F0-ATPase on serine residue; and 3) PKC-α does not mediate depolarization of RPTC mitochondria. This is the first report showing that PKC-α phosphorylates the catalytic subunit of F1F0-ATPase and that PKC-α plays an important role in regulating repair of mitochondrial function.

scholarly journals Effects of GH/IGF on the Aging Mitochondria

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1384 ◽  
Author(s):  
Sher Bahadur Poudel ◽  
Manisha Dixit ◽  
Maria Neginskaya ◽  
Karthik Nagaraj ◽  
Evgeny Pavlov ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Hormone ◽  
Cell Differentiation ◽  
Growth Factor ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Cellular Aging ◽  
Mitochondrial Mass ◽  
Atp Production ◽  
And Function

The mitochondria are key organelles regulating vital processes in the eukaryote cell. A decline in mitochondrial function is one of the hallmarks of aging. Growth hormone (GH) and the insulin-like growth factor-1 (IGF-1) are somatotropic hormones that regulate cellular homeostasis and play significant roles in cell differentiation, function, and survival. In mammals, these hormones peak during puberty and decline gradually during adulthood and aging. Here, we review the evidence that GH and IGF-1 regulate mitochondrial mass and function and contribute to specific processes of cellular aging. Specifically, we discuss the contribution of GH and IGF-1 to mitochondrial biogenesis, respiration and ATP production, oxidative stress, senescence, and apoptosis. Particular emphasis was placed on how these pathways intersect during aging.

scholarly journals Alteration of the Mitochondrial Effects of Ceria Nanoparticles by Gold: An Approach for the Mitochondrial Modulation of Cells Based on Nanomedicine

Nanomaterials ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 744
Author(s):  
Patricia Gutiérrez-Carcedo ◽  
Sergio Navalón ◽  
Rafael Simó ◽  
Xavier Setoain ◽  
Carolina Aparicio-Gómez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Antioxidant Properties ◽  
Antioxidant Effect ◽  
Gold Deposition ◽  
Ceria Nanoparticles ◽  
Atp Production ◽  
Nuclear Respiratory Factor ◽  
Nuclear Respiratory Factor 1 ◽  
Supported Gold Nanoparticles

Ceria nanoparticles are cell compatible antioxidants whose activity can be enhanced by gold deposition and by surface functionalization with positive triphenylphosphonium units to selectively target the mitochondria. The antioxidant properties of these nanoparticles can serve as the basis of a new strategy for the treatment of several disorders exhibiting oxidative stress, such as cancer, diabetes or Alzheimer’s disease. However, all of these pathologies require a specific antioxidant according with their mechanism to remove oxidant species excess in cells and diminish their effect on mitochondrial function. The mechanism through which ceria nanoparticles neutralize oxidative stress and their effect on mitochondrial function have not been characterized yet. In the present study, the mitochondria antioxidant effect of ceria and ceria-supported gold nanoparticles, with or without triphenylphosphonium functionalization, was assessed in HeLa cells. The effect caused by ceria nanoparticles on mitochondria function in terms of mitochondrial membrane potential (∆Ψm), adenosine triphosphate (ATP) production, nuclear respiratory factor 1 (NRF1) and nuclear factor erythroid–2–like 1 (NFE2L1) was reversed by the presence of gold. Furthermore, this effect was enhanced when nanoparticles were functionalized with triphenylphosphonium. Our study illustrates how the mitochondrial antioxidant effect induced by ceria nanoparticles can be modulated by the presence of gold.

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