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Review
. 2016 Jun 28:7:256.
doi: 10.3389/fphys.2016.00256. eCollection 2016.

Carbonylation Modification Regulates Na/K-ATPase Signaling and Salt Sensitivity: A Review and a Hypothesis

Preeya T Shah  1 , Rebecca Martin  1 , Yanling Yan  1 , Joseph I Shapiro  1 , Jiang Liu  1
Affiliations
Review

Carbonylation Modification Regulates Na/K-ATPase Signaling and Salt Sensitivity: A Review and a Hypothesis

Preeya T Shah et al. Front Physiol. .

Abstract

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 tubular Na/K-ATPase signaling and decreased transcellular sodium transport leading to increases in urinary sodium excretion. However, once this system is overstimulated, the signaling, and associated changes in sodium excretion are blunted. This review aims to evaluate ROS-mediated carbonylation of the Na/K-ATPase, and its potential role in the regulation of pump signaling and sodium reabsorption in the renal proximal tubule (RPT).

Keywords: Na/K-ATPase; ROS; protein carbonylation; signaling.

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Figures

Figure 1
Figure 1
Schematic illustration of CTS and ROS mediated sodium handling in RPT and its relation to salt sensitivity. CTS induced intracellular ROS generation and extracellularly generated ROS stimulates Na/K-ATPase/c-Src signaling, protein carbonylation, and transporter redistribution. Pretreatment with NAC blocks this process. ROS1, CTS induced intracellular ROS generation through Na/K-ATPase signaling; ROS2, extracellular ROS generated by glucose oxidase or other stimuli. Please also see Figure 2. RPT, renal proximal tubule; NAC, N-acetyl-L-cysteine.
Figure 2
Figure 2
Illustrated hypothesis of α1 carbonylation on Na/K-ATPase signaling and sodium handling. Panel (A) shows events under physiological stimulation and Panel (B) shows events under pathophysiological overstimulation. ROS1, CTS induced intracellular ROS generation through Na/K-ATPase signaling; ROS2, extracellular ROS generated by glucose oxidase or other stimuli.
See this image and copyright information in PMC

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