Ischemic tolerance conferred to cultured rat neurons by heat shock is not mediated by opening of adenosine triphosphate-sensitive potassium channels.
The effect of sublethal heat shock on the capacity of neurons to resist subsequent ischemia-reperfusion-induced cell injury, was studied in a model of primary rat neuronal cultures, subjected to chemical ischemia. Exposure of the cultures to sublethal heat shock (42 degrees C; 20 min) resulted in elevation in cellular content of heat shock protein (HSP)-70, at 4 h following the shock, and in acquisition of a 15 h 'time window of protection' against ischemia-reperfusion insult, with maximum protection at 4 h. Presence in the culture medium of glibenclamide (2 microM), a blocker of ATP sensitive potassium (K(ATP)) channels, did not abolish the acquisition of protection throughout the entire duration of the acquired 'time window of protection'. The results demonstrate that heat shock induces in neurons a protective mechanism against ischemia-reperfusion insult, probably associated with enhanced expression of HSPs, which does not depend on opening of K(ATP) channels. In this respect, the neuronal 'heat-shock mechanism' for the acquisition of ischemic tolerance differs from the neuronal 'adenosine mechanism' and probably also from the heart 'heat shock mechanism' for the acquisition of protection.
Reshef
A
A
Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Capua
N D
ND
Sperling
O
O
Zoref-Shani
E
E
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D005333:Fetus / Q000166:cytology; D005905:Glyburide / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response / Q000187:drug effects / Q000502:physiology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D009410:Nerve Degeneration / Q000503:physiopathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism*
D018840:HSP70 Heat-Shock Proteins; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D005905:Glyburide