2022  1,200
2021  1,540
2020  1,374
2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 49(2015) N 1 p. 153-160; DOI 10.1134/S0026893315010148 Full Text

I.Yu. Petrushanko1, O.V. Simonenko1, K.M. Burnysheva1, E.A. Klimanova2, E.A. Dergousova2, V.A. Mitkevich1, O.D. Lopina2, A.A. Makarov1*

The ability of cells to adapt to low-oxygen conditions is associated with glutathionylation of Na,K-ATPase

1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
2Faculty of Biology, Moscow State University, Moscow, 119992 Russia

Received - 2014-07-14; Accepted - 2014-07-28

The decrease in the oxygen content of tissues, which is observed in a number of pathological processes, inevitably leads to damage. One of the main causes of cell damage and death in hypoxia is the failure of the systems that maintain the ionic balance. Na,K-ATPase is the main ion-transporting protein in the plasma membrane of animal cells, and its inhibition at low concentrations of oxygen is one of the earliest and most critical events for cell viability. Scientists are currently conducting an active search for regulators of Na,K-ATPase activity. Cardiac glycosides traditionally used for this purpose induce severe side effects, which neces-sitates the search for alternative inhibitors of Na,K-ATPase. We have previously found that glutathionylation of the Na,K-ATPase catalytic subunit leads to a complete inhibition of the enzyme. The present study demonstrates that the substances that increase the level of glutathionylation in Na,K-ATPase, namely, ethyl glutathione (et-GSH), oxidized glutathione (GSSG), and N-acetylcysteine (NAC), enhance cell survival under low-oxygen conditions, prevent ATP depletion, and normalize the redox status of the cells. The following concentration range in which these substances have the maximum protective effect and no pronounced cytotoxic properties was determined to be as follows: 0.2-0.5 mM et-GSH, 0.2-1 mM GSSG, and 10-15 mM NAC. These results demonstrate the prospects of developing methods of protecting tissues from damage under low-oxygen conditions that are based on changes in Na,K-ATPase glutathionylation.

Na,K-ATPase, hypoxia, ischemia, ATP depletion, protection against oxidation, glutathionylation, intracellular redox status