[The ability of cells to adjust to the low oxigen content associated with Na,K-ATPase glutationilation].
Decreasing the amount of oxygen in the tissues under hypoxic and ischemic conditions, observed at a number of pathologic processes, inevitably leads to their damage. One of the main causes of cell damage and death is a violation of the systems maintaining ionic balance. Na,K-ATPaseis a basic ion-transporting protein of animal cell plasma membrane and inhibition of the Na,K-ATPase activity at lower concentrations of oxygen is one of the earliest and most critical events for cell viability. Currently there is an active search for modulators of Na,K-ATPase activity. For this purpose traditionally used cardiac glycosides but the existence of serious adverse effects forced to look for alternative inhibitors of Na,K-ATPase. Previously we have found that the glutathionylation of Na,K-ATPase catalytic subunit leads to a complete-inhibition of the enzyme. In this paper it is shown that the agents which increase the level of Na,K-ATPase glutathionylation: ethyl glutathione (et-GSH), oxidized glutathione (GSSG) and N-acetyl cysteine (NAC), increase cell survival under oxygen deficiency conditions, prevent decline of ATP in the cells and normalize their redox status. Concentration range in which these substances have a maximum protective effect, and does not exhibit cytotoxic properties was defined: for et-GSH 0.2-0.5 mM, for GSSG 0.2-1 mM, for NAC 10 to 15 mM. The results show prospects for development of methods for tissues protection from damage caused by oxygen starvation by varying the degree of Na,K-ATPase glutathionylation.
I Iu
IIu
Petrushanko
O V
OV
Simonenko
K M
KM
Burnysheva
E A
EA
Klimanova
E A
EA
Dergousova
V A
VA
Mit'kevich
O D
OD
Lopina
A A
AA
Makarov
D000111:Acetylcysteine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D020134:Catalytic Domain / Q000187:drug effects; D015687:Cell Hypoxia; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000494:pharmacology; D006801:Humans; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione; D010100:Oxygen; D019803:Glutathione Disulfide; D000111:Acetylcysteine