Reversible oxidation of vicinal-thiols motif in sarcoplasmic reticulum calcium regulatory proteins is involved in muscle fatigue mechanism

Vázquez, Pavel; Tirado-Cortés, Aldo; Álvarez, Rocío; Ronjat, Michel; Amaya, Araceli; Ortega, Alejandro López

doi:10.1016/j.ceca.2016.06.001

Cited by 8 publications

(6 citation statements)

References 46 publications

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“…The redox state of the cytosolic milieu is in a reduced thiol state in physiological conditions and metabolic energy is required to maintained a reduced milieu. A spectrum of cysteines in various peptides can be oxidized resulting in a loss of enzymatic function [e.g., creatine kinase, SERCA, ( 19 , 20 )] or modulation of ion channels [e.g., L-type Ca 2+ channels ( 21 ) and SR Ca 2+ release channels or ryanodine receptors (RyR) ( 22 )]. The cardiac Ryanodine receptor, RyR2 is particularly sensitive to thiol oxidation and has been shown to contain “critical” or “hyperreactive” thiols which when oxidized and reduced, open and close the channel, respectively ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Relaxin Inhibits Ventricular Arrhythmia and Asystole in Rats With Pulmonary Arterial Hypertension

Martin

Vanderpool

Henry

et al. 2021

Front. Cardiovasc. Med.

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Pulmonary arterial hypertension (PAH) leads to right ventricular cardiomyopathy and cardiac dysfunctions where in the clinical setting, cardiac arrest is the likely cause of death, in ~70% of PAH patients. We investigated the cardiac phenotype of PAH hearts and tested the hypothesis that the insulin-like hormone, Relaxin could prevent maladaptive cardiac remodeling and protect against cardiac dysfunctions in a PAH animal model. PAH was induced in rats with sugen (20 mg/kg), hypoxia then normoxia (3-weeks/each); relaxin (RLX = 0, 30 or 400 μg/kg/day, n ≥ 6/group) was delivered subcutaneously (6-weeks) with implanted osmotic mini-pumps. Right ventricle (RV) hemodynamics and Doppler-flow measurements were followed by cardiac isolation, optical mapping, and arrhythmia phenotype. Sugen-hypoxia (SuHx) treated rats developed PAH characterized by higher RV systolic pressures (50 ± 19 vs. 22 ± 5 mmHg), hypertrophy, reduced stroke volume, ventricular fibrillation (VF) (n = 6/11) and bradycardia/arrest (n = 5/11); both cardiac phenotypes were suppressed with dithiothreitol (DTT = 1 mM) (n = 0/2/group) or RLX (low or high dose, n = 0/6/group). PAH hearts developed increased fibrosis that was reversed by RLX-HD, but not RLX-LD. Relaxin decreased Nrf2 and glutathione transferases but not glutathione-reductase. High-dose RLX improved pulmonary arterial compliance (measured by Doppler flow), suppressed VF even after burst-pacing, n = 2/6). Relaxin suppressed VF and asystole through electrical remodeling and by reversing thiol oxidative stress. For the first time, we showed two cardiac phenotypes in PAH animals and their prevention by RLX. Relaxin may modulate maladaptive cardiac remodeling in PAH and protect against arrhythmia and cardiac arrest.

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Section: Discussionmentioning

confidence: 99%

Relaxin Inhibits Ventricular Arrhythmia and Asystole in Rats With Pulmonary Arterial Hypertension

Martin

Vanderpool

Henry

et al. 2021

Front. Cardiovasc. Med.

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“…handling is suggested to play a role in obesity-induced muscle dysfunction through HFD-induced increased production of reactive oxygen species (ROS) which would promote SR Ca 2+ leak through enhanced S-nitrosylation of RYR1 channels [40] and possibly also, impair SERCA function [41,42]. In addition, altered expression and/or efficiency of sarcolipin [30] could also contribute to impair cytosolic Ca 2+ clearance with potentially consequences for muscle metabolism and energy expenditure through activation of Ca 2+ signaling pathways [43,44].…”

Section: Discussionmentioning

confidence: 99%

Preserved Ca2+ handling and excitation–contraction coupling in muscle fibres from diet-induced obese mice

Jaque-Fernández¹,

Beaulant²,

Berthier³

et al. 2020

Diabetologia

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“…However, based on rather complex calculations, it appears that in each RYR, there are at least nine cysteine residues per subunit capable of influencing (positively or negatively) channel gating [ 73 ]. This means that if the cysteine residues are weakly oxidized, the channel is closed; following increasing but not overstated oxidation, the channel is activated, and if oxidation continues, the channel is inactivated; perhaps in this way, the phenomenon of fatigue caused by a state of distress and excessive oxidation/reduction in the so-called vicinal thiol groups (VGT) present on SERCA could also be justified [ 74 ].…”

Section: Can Skeletal Muscle Be a Model For Testing The Hypothesis?mentioning

confidence: 99%

H2O2/Ca2+/Zn2+ Complex Can Be Considered a “Collaborative Sensor” of the Mitochondrial Capacity?

et al. 2022

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In order to maintain a state of well-being, the cell needs a functional control center that allows it to respond to changes in the internal and surrounding environments and, at the same time, carry out the necessary metabolic functions. In this review, we identify the mitochondrion as such an “agora”, in which three main messengers are able to collaborate and activate adaptive response mechanisms. Such response generators, which we have identified as H2O2, Ca2+, and Zn2+, are capable of “reading” the environment and talking to each other in cooperation with the mitochondrion. In this manner, these messengers exchange information and generate a holistic response of the whole cell, dependent on its functional state. In this review, to corroborate this claim, we analyzed the role these actors, which in the review we call “sensors”, play in the regulation of skeletal muscle contractile capacities chosen as a model of crosstalk between Ca2+, Zn2+, and H2O2.

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Reversible oxidation of vicinal-thiols motif in sarcoplasmic reticulum calcium regulatory proteins is involved in muscle fatigue mechanism

Cited by 8 publications

References 46 publications

Relaxin Inhibits Ventricular Arrhythmia and Asystole in Rats With Pulmonary Arterial Hypertension

Relaxin Inhibits Ventricular Arrhythmia and Asystole in Rats With Pulmonary Arterial Hypertension

Preserved Ca2+ handling and excitation–contraction coupling in muscle fibres from diet-induced obese mice

H2O2/Ca2+/Zn2+ Complex Can Be Considered a “Collaborative Sensor” of the Mitochondrial Capacity?

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