Abstract 104: Effects of Pinacidil and Ca 2 + on Sodium-loaded Rat Heart Mitochondria

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Sergey M Korotkov ◽  
Vladimir P Nesterov ◽  
Irina V Brailovskaya ◽  
Larisa V Emelyanova ◽  
Svetlana A Konovalova ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Rat Heart ◽  
Mitochondrial Membrane ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion ◽  
Potassium Acetate ◽  
Heart Mitochondria ◽  
Inner Mitochondrial Membrane ◽  
Rat Heart Mitochondria ◽  
Acetate Medium

Deterioration of the contractile parameters of the heart muscle caused by ischemia and followed reperfusion is known as the main postoperative complication which is related to Ca 2+ and Na + overload in cardiomyocytes and mitochondria. Pinacidil reduced the overload in ischemia/reperfusion experiments. The mechanism of this phenomenon is still not clear. We hypothesized that increased ion permeability of the inner mitochondrial membrane (IMM) followed drop of electrochemical potential (ΔΨ mito ) can reduce the calcium. The aim of the study was to elucidate the effect of pinacidil (100 μM) and Ca 2+ (100 μM ) on swelling, oxygen consumption and ΔΨ mito of isolated sodium-loaded rat heart mitochondria (RHM(Na)) energized glutamate and malate. Pinacidil significantly enchanced the permeability of IMM to protons in ammonium nitrate medium. Also increased swelling of RHM(Na) energized with substrates in potassium acetate medium revealed that pinacidil increased potassium transport into matrix. Pinacidil stimulated oxygen consumption of RHM(Na) in State 4 and detained Ca 2+ -induced dissipation of ΔΨ mito . Under condition of Ca 2+ and Na + overload simulating ischemia/reperfusion, RHM(Na) oxygen consumption was not affected with pinacidil in State 3 and in the presence of 2,4-dinitrophenol. Cyclosporin A and ADP, the inhibitors of mitochondrial permeability transition pore (MPTP), markedly decreased Ca 2+ - induced swelling of RHM(Na) in nitrate ammonium or potassium acetate medium in the presence of pinacidil. Carboxyatractyloside, an inhibitor of cytosolic side-specific adenine nucleotide translocase, eliminated a pinacidil-stimulated oxygen consumption of succinate-energized RHMNa in State 4 regardless of the presence of Ca 2+ . Pinacidil was also concluded to accelerat potassium flux into energized RHM(Na) and promot MPTP opening in the low conduction state. Based on our data we suggested that the effect of pharmacological preconditioning induced by pinacidil could be due to it’s direct effect on mitochondria which is connected with above stimulation of the potassium permeability of the inner mitochondrial membrane and following reduce of the ΔΨ mito that thus prevent calcium overload of cardiomyocytes after ischemia/reperfusion in turn.

scholarly journals Astaxanthin Inhibits Mitochondrial Permeability Transition Pore Opening in Rat Heart Mitochondria

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 576 ◽  
Author(s):  
Yulia Baburina ◽  
Roman Krestinin ◽  
Irina Odinokova ◽  
Linda Sotnikova ◽  
Alexey Kruglov ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Heart ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Heart Mitochondria ◽  
Inner Mitochondrial Membrane ◽  
Mitochondrial Permeability ◽  
Rat Heart Mitochondria

The mitochondrion is the main organelle of oxidative stress in cells. Increased permeability of the inner mitochondrial membrane is a key phenomenon in cell death. Changes in membrane permeability result from the opening of the mitochondrial permeability transition pore (mPTP), a large-conductance channel that forms after the overload of mitochondria with Ca2+ or in response to oxidative stress. The ketocarotenoid astaxanthin (AST) is a potent antioxidant that is capable of maintaining the integrity of mitochondria by preventing oxidative stress. In the present work, the effect of AST on the functioning of mPTP was studied. It was found that AST was able to inhibit the opening of mPTP, slowing down the swelling of mitochondria by both direct addition to mitochondria and administration. AST treatment changed the level of mPTP regulatory proteins in isolated rat heart mitochondria. Consequently, AST can protect mitochondria from changes in the induced permeability of the inner membrane. AST inhibited serine/threonine protein kinase B (Akt)/cAMP-responsive element-binding protein (CREB) signaling pathways in mitochondria, which led to the prevention of mPTP opening. Since AST improves the resistance of rat heart mitochondria to Ca2+-dependent stress, it can be assumed that after further studies, this antioxidant will be considered an effective tool for improving the functioning of the heart muscle in general under normal and medical conditions.

scholarly journals Effects of pinacidil and calcium on succinate-energized rat heart mitochondria in the presence of rotenone

2019 ◽  
Vol 487 (4) ◽  
pp. 460-464
Author(s):  
S. M. Korotkov ◽  
I. V. Brailovskaya ◽  
V. P. Nesterov ◽  
S. I. Soroko
Keyword(s):  
Rat Heart ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Heart Mitochondria ◽  
Inner Membrane ◽  
Muscle Ischemia ◽  
Rat Heart Mitochondria

The effect of pinacidil was studied on calcium-loaded rat heart mitochondria (RHM) in the presence of succinate and rotenone. In experiments with pinacidil, the swelling of these mitochondria increased in media with NH4NO3 or K‑acetate, but the inner membrane potential DΨmito and state 3 or 2,4-dinitrophenol-uncoupled respiration of these organelles were decreased due to opening of the mitochondrial permeability transition pore in the inner membrane. These effects were inhibited by cyclosporin A and ADP. It was concluded that the protective effect of pinacidil in the cardiac muscle ischemia/reperfusion may be associated with stimulation mitochondrial swelling and a decrease in RHM calcium overload resulted in a decrease in DΨmito due to the soft uncoupling pinacidil effect.

Ca2+ Accumulation in Isolated Rat Heart Mitochondria under Maintenance of Mitochondrial Membrane Potential

2016 ◽  
Vol 7 (4) ◽  
pp. 309-319
Author(s):  
Alina Yu. Budko ◽  
Nataliya A. Strutynska ◽  
Iryna Yu. Okhay ◽  
Olena M. Semenykhina ◽  
Vadim F. Sagach
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Rat Heart ◽  
Mitochondrial Membrane ◽  
Isolated Rat Heart ◽  
Heart Mitochondria ◽  
Rat Heart Mitochondria ◽  
Isolated Rat

Isolated rat heart mitochondria and whole rat heart as models for mitochondrial cold ischemia-reperfusion injury

2000 ◽  
Vol 32 (1) ◽  
pp. 45 ◽  
Author(s):  
A.V Kuznetsov ◽  
G Brandacher ◽  
W Steurer ◽  
R Margreiter ◽  
E Gnaiger
Keyword(s):  
Reperfusion Injury ◽  
Rat Heart ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Isolated Rat Heart ◽  
Heart Mitochondria ◽  
Cold Ischemia ◽  
Rat Heart Mitochondria ◽  
Isolated Rat

scholarly journals Ca2+ stimulates both the respiratory and phosphorylation subsystems in rat heart mitochondria

1996 ◽  
Vol 320 (1) ◽  
pp. 329-334 ◽  
Author(s):  
Vida MILDAZIENE ◽  
Rasa BANIENE ◽  
Zita NAUCIENE ◽  
Ausra MARCINKEVICIUTE ◽  
Ramune MORKUNIENE ◽  
...  
Keyword(s):  
Rat Heart ◽  
Mitochondrial Membrane ◽  
Isolated Rat Heart ◽  
Heart Mitochondria ◽  
Proton Leak ◽  
Succinate Oxidation ◽  
Kinetic Dependence ◽  
Intermediate States ◽  
Rat Heart Mitochondria ◽  
Stimulation Of

Stimulation of mitochondrial respiration by physiological concentrations of Ca2+ was studied to determine which components of oxidative phosphorylation are affected by Ca2+. The kinetic dependence of the respiratory chain, phosphorylation subsystem and proton leak on the mitochondrial membrane potential in isolated rat heart mitochondria respiring on 2-oxoglutarate or succinate was measured at two different concentrations of external free Ca2+. The results show that proton leak is not directly affected by Ca2+, but that both the respiratory and phosphorylation systems can be directly stimulated by Ca2+ depending on conditions. Although Ca2+ directly stimulates the phosphorylation system, this has relatively little effect on respiration rate with 2-oxoglutarate in States 3 and 4 because the subsystem has little control over respiration. However, in intermediate states, the phosphorylation system has greater control and Ca2+ stimulation of this system contributes substantially to the stimulation of respiration and phosphorylation. In the case of succinate oxidation neither the respiratory subsystem nor the phosphorylation system is stimulated by Ca2+.

Simultaneous Measurement of Oxygen Consumption and 13C16O2 Production From 13C-Pyruvate in Diabetic Rat Heart Mitochondria

1997 ◽  
pp. 269-275 ◽  
Author(s):  
Nicolai M. Doliba ◽  
Ian R. Sweet ◽  
Andriy Babsky ◽  
Nataliya Doliba ◽  
Robert E. Forster ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Simultaneous Measurement ◽  
Rat Heart ◽  
Heart Mitochondria ◽  
Diabetic Rat ◽  
Rat Heart Mitochondria

Astragalus Membranaceus and Polygonum Multijlorum Protect Rat Heart Mitochondria Against Lipid Peroxidation

1994 ◽  
Vol 22 (01) ◽  
pp. 63-70 ◽  
Author(s):  
C. Y. Hong ◽  
Y. C. Lo ◽  
F. C. Tan ◽  
Y. H. Wei ◽  
C. F. Chen
Keyword(s):  
Lipid Peroxidation ◽  
Oxygen Consumption ◽  
Rat Heart ◽  
Isolated Rat Heart ◽  
Heart Mitochondria ◽  
Astragalus Membranaceus ◽  
Chinese Medicinal Herbs ◽  
Inhibit Lipid Peroxidation ◽  
Mitochondrial Suspension ◽  
Rat Heart Mitochondria

We isolated rat heart mitochondria and induced lipid peroxidation with ADP and FeSO4.Oxygen consumption and MDA formation were measured for quantitating the amount of lipid peroxidation. Using these methods, we screened the water extracts of 14 Chinese medicinal herbs for their effect on lipid peroxidation. It was found that Astragalus membranaceus inhibited 42.1 ± 3.4% of oxygen consumption and 39.8 ± 3.2% of MDA production at concentration of 2 mg dried herb/ml mitochondrial suspension. At the same concentration, Polygonum multijlorum inhibited 52.1 ± 7.3% of oxygen consumption and 50.9 ± 5.3% of MDA production. Other herbs did not inhibit lipid peroxidation to 50% of control at concentration up to 6 mg dried herb/ml mitochondrial suspension. Purification and identification of the active component(s) in Astragalus membranaceus and Polygonum multijlorum as well as their clinical application await further studies.

scholarly journals Isoproterenol-Induced Permeability Transition Pore-Related Dysfunction of Heart Mitochondria Is Attenuated by Astaxanthin

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 437
Author(s):  
Roman Krestinin ◽  
Yulia Baburina ◽  
Irina Odinokova ◽  
Alexey Kruglov ◽  
Irina Fadeeva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Heart ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Antioxidant Defense System ◽  
Heart Mitochondria ◽  
Main Function ◽  
Retention Capacity ◽  
Rat Heart Mitochondria

Mitochondria are key organelles of the cell because their main function is the capture of energy-rich substrates from the cytoplasm and oxidative cleavage with the generation of carbon dioxide and water, processes that are coupled with the synthesis of ATP. Mitochondria are subject to oxidative stress through the formation of the mitochondrial permeability transition pore (mPTP). Various antioxidants are used to reduce damage caused by oxidative stress and to improve the protection of the antioxidant system. Astaxanthin (AST) is considered to be a dietary antioxidant, which is able to reduce oxidative stress and enhance the antioxidant defense system. In the present investigation, the effect of AST on the functional state of rat heart mitochondria impaired by isoproterenol (ISO) under mPTP functioning was examined. It was found that AST raised mitochondrial respiration, the Ca2+ retention capacity (CRC), and the rate of TPP+ influx in rat heart mitochondria (RHM) isolated from ISO-injected rats. However, the level of reactive oxygen species (ROS) production increased. In addition, the concentrations of cardiolipin (CL), Mn-SOD2, and the proteins regulating mPTP rose after the injection of ISO in RHM pretreated with AST. Based on the data obtained, we suggest that AST has a protective effect in rat heart mitochondria.

scholarly journals Diabetes-associated dysregulation ofO-GlcNAcylation in rat cardiac mitochondria

2015 ◽  
Vol 112 (19) ◽  
pp. 6050-6055 ◽  
Author(s):  
Partha S. Banerjee ◽  
Junfeng Ma ◽  
Gerald W. Hart
Keyword(s):  
Mitochondrial Dysfunction ◽  
Rat Heart ◽  
Mitochondrial Membrane ◽  
Diabetic Rats ◽  
Neonatal Rat ◽  
Heart Mitochondria ◽  
Cardiac Mitochondria ◽  
Rat Cardiomyocytes ◽  
Pyrimidine Nucleotide ◽  
Rat Heart Mitochondria

Elevated mitochondrialO-GlcNAcylation caused by hyperglycemia, as occurs in diabetes, significantly contributes to mitochondrial dysfunction and to diabetic cardiomyopathy. However, little is known about the enzymology of mitochondrialO-GlcNAcylation. Herein, we investigated the enzymes responsible for cyclingO-GlcNAc on mitochondrial proteins and studied the mitochondrial transport of UDP-GlcNAc. Analyses of purified rat heart mitochondria from normal and streptozocin-treated diabetic rats show increased mitochondrialO-GlcNAc transferase (OGT) and a concomitant decrease in the mito-specific O-GlcNAcase (OGA). Strikingly, OGT is mislocalized in cardiac mitochondria from diabetic rats. Interaction of OGT and complex IV observed in normal rat heart mitochondria is visibly reduced in diabetic samples, where OGT is mislocalized to the matrix. Live cell OGA activity assays establish the presence of O-GlcNAcase within the mitochondria. Furthermore, we establish that the inner mitochondrial membrane transporter, pyrimidine nucleotide carrier, transports UDP-GlcNAc from the cytosol to the inside of the mitochondria. Knockdown of this transporter substantially lowers mitochondrialO-GlcNAcylation. Inhibition of OGT or OGA activity within neonatal rat cardiomyocytes significantly affects energy production, mitochondrial membrane potential, and mitochondrial oxygen consumption. These data suggest that cardiac mitochondria not only have robustO-GlcNAc cycling, but also that dysregulation ofO-GlcNAcylation likely plays a key role in mitochondrial dysfunction associated with diabetes.

scholarly journals Astaxanthin Prevents Mitochondrial Impairment Induced by Isoproterenol in Isolated Rat Heart Mitochondria

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 262 ◽  
Author(s):  
Olga Krestinina ◽  
Yulia Baburina ◽  
Roman Krestinin ◽  
Irina Odinokova ◽  
Irina Fadeeva ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Rat Heart ◽  
Adenine Nucleotide ◽  
Heart Function ◽  
Isolated Rat Heart ◽  
Heart Mitochondria ◽  
Cyclophilin D ◽  
Inner Mitochondrial Membrane ◽  
Respiratory Chain Complexes ◽  
Rat Heart Mitochondria

Mitochondria are considered to be a power station of the cell. It is known that they play a major role in both normal and pathological heart function. Alterations in mitochondrial bioenergetics are one of the main causes of the origin and progression of heart failure since they have an inhibitory effect on the activity of respiratory complexes in the inner mitochondrial membrane. Astaxanthin (AST) is a xanthophyll carotenoid of mainly marine origin. It has both lipophilic and hydrophilic properties and may prevent mitochondrial dysfunction by permeating the cell membrane and co-localizing within mitochondria. The carotenoid suppresses oxidative stress-induced mitochondrial dysfunction and the development of diseases. In the present study, it was found that the preliminary oral administration of AST upregulated the activity of respiratory chain complexes and ATP synthase and the level of their main subunits, thereby improving the respiration of rat heart mitochondria (RHM) in the heart injured by isoproterenol (ISO). AST decreased the level of cyclophilin D (CyP-D) and increased the level of adenine nucleotide translocase (ANT) in this condition. It was concluded that AST could be considered as a potential mitochondrial-targeted agent in the therapy of pathological conditions associated with oxidative damage and mitochondrial dysfunction. AST, as a dietary supplement, has a potential in the prevention of cardiovascular diseases.

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