2013
DOI: 10.1089/ars.2012.5057
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HNO Enhances SERCA2a Activity and Cardiomyocyte Function by Promoting Redox-Dependent Phospholamban Oligomerization

Abstract: Aims: Nitroxyl (HNO) interacts with thiols to act as a redox-sensitive modulator of protein function. It enhances sarcoplasmic reticular Ca 2+ uptake and myofilament Ca 2+ sensitivity, improving cardiac contractility. This activity has led to clinical testing of HNO donors for heart failure. Here we tested whether HNO alters the inhibitory interaction between phospholamban (PLN) and the sarcoplasmic reticulum Ca 2+ -ATPase (SERCA2a) in a redox-dependent manner, improving Ca 2+ handling in isolated myocytes/hea… Show more

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Cited by 72 publications
(70 citation statements)
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“…Thus it is not surprising that the TauTKO heart exhibits differences from other models of heart failure (no change in phospholamban and SERCA2 expression and reduced phospholamban phosphorylation), as taurine deficiency not only alters the activity of the protein kinases and protein phosphatases, but also modulates both [Ca 2ϩ ] i and the Ca 2ϩ dependence of the SR Ca 2ϩ ATPase. However, it is also possible that the activity of the SR Ca 2ϩ ATPase of the TauTKO heart might be altered by the oligomerization state of phospholamban (42).…”
Section: Discussionmentioning
confidence: 99%
“…Thus it is not surprising that the TauTKO heart exhibits differences from other models of heart failure (no change in phospholamban and SERCA2 expression and reduced phospholamban phosphorylation), as taurine deficiency not only alters the activity of the protein kinases and protein phosphatases, but also modulates both [Ca 2ϩ ] i and the Ca 2ϩ dependence of the SR Ca 2ϩ ATPase. However, it is also possible that the activity of the SR Ca 2ϩ ATPase of the TauTKO heart might be altered by the oligomerization state of phospholamban (42).…”
Section: Discussionmentioning
confidence: 99%
“…Unlike NO•, HNO is resistant to ROS scavenging, does not develop tolerance to its actions, and may target oxidized sGC. 9,12,19,44,45 HNO also has a unique ability to enhance LV function, 8,16,46,47 considered dependent on both sGC-independent and sGC-dependent mechanisms. …”
Section: -Nca Treatment Protects Against Diabetes Mellitus-induced Cmentioning
confidence: 99%
“…For example, we have shown that RNS (specifically nitroxyl) modifies PLB cysteines to increase PLB pentamer formation, decreasing monomeric PLB (the form that inhibits SERCA2a) and resulting in a faster Ca 2+ transient decline (Sivakumaran et al 2013; Kohr et al 2010). …”
Section: Introductionmentioning
confidence: 99%