The functional significance of redox-mediated intersubunit cross-linking in regulation of human type 2 ryanodine receptor.

ABSTRACT: The type 2 ryanodine receptor (RyR2) plays a key role in the cardiac intracellular calcium (Ca²⁺) regulation. We have previously shown that oxidative stress activates RyR2 in rabbit cardiomyocytes by promoting the formation of disulfide bonds between neighboring RyR2 subunits. However, the functional significance of this redox modification for human RyR2 (hRyR2) remains largely unknown. Here, we studied the redox regulation of hRyR2 in HEK293 cells transiently expressing the ryr2 gene. Analysis of hRyR2 cross-linking and of the redox-GFP readout response to diamide oxidation revealed that hRyR2 cysteines involved in the intersubunit cross-linking are highly sensitive to oxidative stress. In parallel experiments, the effect of diamide on endoplasmic reticulum (ER) Ca²⁺

SUBMITTER: Nikolaienko R 

PROVIDER: S-EPMC7522892 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature