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 oxid e donor sodium nitroprusside, to enzymatically generated reactive oxyg en 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 ce ll lysis from nitric oxide (0.45 mM sodium nitroprusside) by 70%, from reactive oxygen intermediates (12 mU xanthine oxidase and 0.05 mM hyp oxanthine) by 80% and from streptozotocin (1.5 mM) by 90%. Heat shock induced resistance was observed immediately after termination of the 9 0 min culture at 43 degrees C and correlated with enhanced expression of hsp70. The occurrence of DNA strand breaks, a major early consequen ce of nitric oxide, reactive oxygen intermediates, or streptozotocin a ction, was not suppressed by heat shock treatment. However, the deplet ion of NAD(+), the major cause of radical induced islet cell death, wa s suppressed after heat shock (P < 0.01). We conclude that pancreatic islet cells can rapidly activate defence mechanisms against nitric oxi de, 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-rib ose) polymerase activation.