Medicine and Health Sciences Commons^™

Protein Carbonylation Of An Amino Acid Residue Of The Na/K‐Atpase Α1 Subunit Determines Na/K‐Atpase Signaling And Sodium Transport In Renal Proximal Tubular Cells, Yanling Yan, Anna P. Shapiro, Brahma R. Mopidevi, Muhammad Chaudhry, Kyle Maxwell, Steven T. Haller, Christopher A. Drummond, David J. Keendey, Jiang Tian, Deepak Malhorta, Zijian Xie, Joseph I. Shapiro Md, Jiang Liu

Biochemistry and Microbiology

Background We have demonstrated that cardiotonic steroids, such as ouabain, signaling through the Na/K‐ATPase, regulate sodium reabsorption in the renal proximal tubule. By direct carbonylation modification of the Pro222 residue in the actuator (A) domain of pig Na/K‐ATPase α1 subunit, reactive oxygen species are required for ouabain‐stimulated Na/K‐ATPase/c‐Src signaling and subsequent regulation of active transepithelial ²²Na⁺ transport. In the present study we sought to determine the functional role of Pro222 carbonylation in Na/K‐ATPase signaling and sodium handling.

Methods and Results Stable pig α1 knockdown LLC‐PK1‐originated PY‐17 cells were rescued by expressing wild‐type rat α1 and rat α1 with …

Carbonylation Modification Regulates Na/K-At Pasesignaling And Salt Sensitivity: A Review And A Hypothesis, Preeya Shah Phd, Rebecca Martin, Yanling Yan, Joseph I. Shapiro Md, Jiang Liu

Biochemistry and Microbiology

Na/K-ATPase signaling has been implicated in different physiological and pathophysiological conditions. Accumulating evidence indicates that oxidative stress not only regulates the Na/K-ATPase enzymatic activity, but also regulates its signaling and other functions. While cardiotonic steroids (CTS)-induced increase in reactive oxygen species (ROS) generation is an intermediate step in CTS-mediated Na/K-ATPase signaling, increase in ROS alone also stimulates Na/K-ATPase signaling. Based on literature and our observations, we hypothesize that ROS have biphasic effects on Na/K-ATPase signaling, transcellular sodium transport, and urinary sodium excretion. Oxidative modulation, in particular site specific carbonylation of the Na/K-ATPase α1 subunit, is a critical step in proximal …