FXYD Proteins Reverse Inhibition of the Na+-K+ Pump Mediated by Glutathionylation of Its β1 Subunit

Abstract

We have reported that Na ؉ -K ؉ pump ␤ 1 subunit glutathionylation induced by oxidative signals causes pump inhibition in a previous study. In the present study, we found that ␤ 1 subunit glutathionylation and pump inhibition could be reversed by exposing myocytes to exogenous wild-type FXYD3. A cysteine-free FXYD3 derivative had no effect. Similar results were obtained with wild-type and mutant FXYD proteins expressed in oocytes. Glutathionylation of the ␤ 1 subunit was increased in myocardium from FXYD1 ؊/؊ mice. In conclusion, there is a dependence of Na

Role of phospholemman and the 70 kDa inhibitor protein in regulating Na+/K+ ATPase activity in pulmonary artery smooth muscle cells under U46619 stimulation

“…Inhibition of GRX1 under oxidative stress has also been suggested by Heshemy et al [28]. To ascertain the role of PLM in this scenario, we performed studies with liposomes recon- [12] showed that the ATPase activity was proportional with the level of glutathionylation of the pump, but we have not found such proportionality after treatment of the cells with U46619. It is also well established that oxidant stress during ischemic condition may cause accumulation of substances that inhibit membrane transporter such as NKA.…”

“…2B, lane 1), but the expected glutathionylation signal was quite different after its inhibition. Bibert et al [12] showed that recombinant FXYD3 facilitated the deglutathionylation of NKA in Xenopus oocytes. We found that glutathionylation of PLM was induced from baseline by exposing the cells to U46619.…”

“…It may provide an alternative to phosphorylation of the NKA or associated FXYD because the pump's subunits contain residues that can be oxidized (e.g. the sulfhydryl group) [12] and it has been shown that NKA in skeletal muscle is redox sensitive [13]. Bibert et al [12] recently showed that angiotensin II induces PKC activity and that leads to ROS generation, which subsequently causes glutathionylation of the b subunit and hence inhibits NKA activity.…”

“…the sulfhydryl group) [12] and it has been shown that NKA in skeletal muscle is redox sensitive [13]. Bibert et al [12] recently showed that angiotensin II induces PKC activity and that leads to ROS generation, which subsequently causes glutathionylation of the b subunit and hence inhibits NKA activity. On the other hand, it has been shown that oxidant stress can also activates NKA activity.…”

S-Glutathionylation of Ion Channels: Insights into the Regulation of Channel Functions, Thiol Modification Crosstalk, and Mechanosensing

“…In addition, the application of peroxynitrite (ONOO -) or Snitrosoglutathione (GSNO, 10-500 lM) to induce S-glutathionylation is also found in the literature (12,38,125,129). The application of peroxynitrite is of high physiological relevance but as peroxynitrite can also induce other modification including S-nitrosylation, additional experiments should be performed to further dissect the exact modification mechanism.…”