Oxidative stress in early metabolic syndrome impairs cardiac RyR2 and SERCA2a activity and modifies the interplay of these proteins during Ca 2+ waves

We investigated how oxidative stress (OS) alters Ca handling in ventricular myocytes in early metabolic syndrome (MetS) in sucrose-fed rats. The effects of -acetyl cysteine (NAC) or dl-Dithiothreitol (DTT) on systolic Ca transients (SCaTs), diastolic Ca sparks (CaS) and Ca waves (CaW), recorded by c...

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Published in:Archives of physiology and biochemistry 2021-03, p.1
Main Authors: Gómez-Viquez, Norma Leticia, Balderas-Villalobos, Jaime, Bello-Sánchez, Ma Dolores, Mayorga-Luna, Maritza, Mailloux-Salinas, Patrick, García-Castañeda, Maricela, Ríos-Pérez, Erick Benjamín, Mártinez-Ávila, Marco Antonio, Camacho-Castillo, Luz Del Carmen, Bravo, Guadalupe, Ávila, Guillermo, Altamirano, Julio, Carvajal, Karla
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Language:English
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Summary:We investigated how oxidative stress (OS) alters Ca handling in ventricular myocytes in early metabolic syndrome (MetS) in sucrose-fed rats. The effects of -acetyl cysteine (NAC) or dl-Dithiothreitol (DTT) on systolic Ca transients (SCaTs), diastolic Ca sparks (CaS) and Ca waves (CaW), recorded by confocal techniques, and L-type Ca current (I ), assessed by whole-cell patch clamp, were evaluated in MetS and Control cells. MetS myocytes exhibited decreased SCaTs and CaS frequency but unaffected CaW propagation. In Control cells, NAC/DTT reduced RyR2/SERCA2a activity blunting SCaTs, CaS frequency and CaW propagation, suggesting that basal ROS optimised Ca signalling by maintaining RyR2/SERCA2a function and that these proteins facilitate CaW propagation. Conversely, NAC/DTT in MetS recovered RyR2/SERCA2a function, improving SCaTs and CaS frequency, but unexpectedly decreasing CaW propagation. We hypothesised that OS decreases RyR2/SERCA2a activity at early MetS, and while decreased SERCA2a favours CaW propagation, diminished RyR2 restrains it.
ISSN:1744-4160