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Involvement Of Reactive Oxygen Species In A Feed-Forward Mechanism Of Na/K-Atpase Mediated Signaling, Yanling Yan, Anna P. Shapiro, Steven Haller, Vinal Katragadda, Lijun Liu, Jiang Tian, Venkatesha Basrur, Deepak Malhotra, Zi-Jian Xie, Nader G. Abraham, Joseph I. Shapiro Md, Jiang Liu

Biochemistry and Microbiology

Cardiotonic steroids (such as ouabain) signaling through Na/K-ATPase regulate sodium reabsorption in the renal proximal tubule. We report here that reactive oxygen species are required to initiate ouabain-stimulated Na/K-ATPase·c-Src signaling. Pretreatment with the antioxidant N-acetyl-L-cysteine prevented ouabain-stimulated Na/K-ATPase·c-Src signaling, protein carbonylation, redistribution of Na/K-ATPase and sodium/proton exchanger isoform 3, and inhibition of active transepithelial ²²Na⁺ transport. Disruption of the Na/K-ATPase·c-Src signaling complex attenuated ouabain-stimulated protein carbonylation. Ouabain-stimulated protein carbonylation is reversed after removal of ouabain, and this reversibility is largely independent of de novo protein synthesis and degradation by either the lysosome or the proteasome pathways. Furthermore, …