Amelioration of hypoxic and hypoglycemic damage to cerebral endothelial cells. Effects of heat shock pretreatment.
Induction of the 70 kDa heat shock protein (HSP70) by hypoxia and/or hypoglycemia and the effects of prior heat shock on injury owing to hypoxia and/or hypoglycemia were studied in rat cerebral endothelial cells. Hypoxia and/or hypoglycemia treatment resulted in increased expression of HSP70 only when such treatment was sufficient to cause detectable injury and when the initial treatment was followed by exposure of the cells to 24 h of normoxia and normoglycemia. Heat shock induced 24 h prior to treatment with 48 h of hypoxia slightly reduced endothelial cell damage as measured by fraction of lactate dehydrogenase release (10% decrease in injury). There was a more dramatic effect of prior heat shock on the moderate damage produced by 12 h of combined hypoxia and hypoglycemia (45% decrease), whereas the severe damage produced by 24 h of hypoxia and hypoglycemia was decreased by prior heat shock by only 16%. These results indicate that the hypoxia and hypoglycemia occurring in conjunction with ischemia are more likely to result in heat shock protein expression when there is injury to the tissue. Furthermore, heat shock protects cerebral endothelial cells from hypoxia and hypoglycemia either by slowing the initial development of injury or by delaying the onset of injury.
Gobbel
G T
GT
Department of Neurological Surgery, University of California, San Francisco 94143, USA.
Chan
T Y
TY
Chan
P H
PH
D000818:Animals; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D006358:Hot Temperature; D007003:Hypoglycemia / Q000378:metabolism / Q000473:pathology*; D002534:Hypoxia, Brain / Q000378:metabolism / Q000473:pathology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000473:pathology
D018840:HSP70 Heat-Shock Proteins; D007770:L-Lactate Dehydrogenase