Inhibition of GSK-3β decreases the ischemia-induced death of renal cells.
Pharmacological preconditioning with insulin and lithium ions prevented the death of renal cells under conditions of ischemia/reperfusion. Preincubation of cells with insulin or lithium ions decreased production of reactive oxygen species after ischemia/reoxygenation. These agents also prevented the development of mitochondrial dysfunction in renal cells induced by ischemia/reoxygenation. It was hypothesized that the protective effects of these agents are related to inhibition of glycogen synthase kinase-3(. This enzyme is inactivated upon phosphorylation of serine residue in position 9. We found that in vivo administration of lithium ions to animals before renal ischemia prevents the development of kidney failure.
A. N. Belozerskii Institute of Physicochemical Biology, M. V. Lomonosov Moscow State University, Moscow, Russia.
A K
AK
Vasileva
E Y
EY
Plotnikov
A V
AV
Kazachenko
V I
VI
Kirpatovsky
D B
DB
Zorov
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002478:Cells, Cultured; D004586:Electrophoresis; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D000071679:Glycogen Synthase Kinase 3 beta; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000166:cytology* / Q000473:pathology*; D008094:Lithium / Q000494:pharmacology; D018613:Microscopy, Confocal; D028361:Mitochondrial Diseases / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D051437:Renal Insufficiency / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D015427:Reperfusion Injury / Q000150:complications / Q000473:pathology*
D007328:Insulin; D017382:Reactive Oxygen Species; D008094:Lithium; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3