Heat shock induces resistance in rat pancreatic islet cells against nitric oxide, oxygen radicals and streptozotocin toxicity in vitro.
When cultures of pancreatic islet cells are exposed to the nitric oxide donor sodium nitroprusside, to enzymatically generated reactive oxygen intermediates or to streptozotocin cell lysis occurs after 4-12 h. We report here that a heat shock at 43 degrees C for 90 min reduces cell lysis from nitric oxide (0.45 mM sodium nitroprusside) by 70%, from reactive oxygen intermediates (12 mU xanthine oxidase and 0.05 mM hypoxanthine) by 80% and from streptozotocin (1.5 mM) by 90%. Heat shock induced resistance was observed immediately after termination of the 90 min culture at 43 degrees C and correlated with enhanced expression of hsp70. The occurrence of DNA strand breaks, a major early consequence of nitric oxide, reactive oxygen intermediates, or streptozotocin action, was not suppressed by heat shock treatment. However, the depletion of NAD+, the major cause of radical induced islet cell death, was suppressed after heat shock (P < 0.01). We conclude that pancreatic islet cells can rapidly activate defence mechanisms against nitric oxide, reactive oxygen intermediates and streptozotocin by culture at 43 degrees C. Islet cell survival is due to the prevention of lethal NAD+ depletion during DNA repair, probably by slowing down poly(ADP-ribose)polymerase activation.
Bellmann
K
K
Diabetes Research Institute, Universität of Düsseldorf, Germany.
Wenz
A
A
Radons
J
J
Burkart
V
V
Kleemann
R
R
Kolb
H
H
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006358:Hot Temperature; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009243:NAD / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D013311:Streptozocin / Q000633:toxicity*; D013997:Time Factors
D018840:HSP70 Heat-Shock Proteins; D017382:Reactive Oxygen Species; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D009569:Nitric Oxide; D013311:Streptozocin