Heat shock protein induction in rat pancreatic islets by recombinant human interleukin 1 beta.
Interleukin 1 beta, potentiated by tumour necrosis factor alpha, is cytotoxic to pancreatic Beta cells in vitro. We have hypothesized that interleukin 1 beta induces oxygen free radicals in Beta cells. Since cytotoxicity induced by free radicals and by heat may activate the same cellular repair mechanism (the heat shock response), the aim of this study was to investigate the pattern of protein synthesis in isolated islets after exposure to interleukin 1 beta (150 pg/ml, 24 h), tumour necrosis factor alpha (50 ng/ml, 24 h) heat shock (43 degrees C, 30 min) and H2O2 (0.1 mmol/l, 20 min). By polyacrylamide gel electrophoresis, autoradiography, Western-blot analysis and partial peptide mapping of 35S-methionine labelled islets, interleukin 1 beta was found to induce a 73 kilodalton protein belonging to the heat shock protein family heat shock protein 70, a heat shock protein 90, and haem oxygenase. A minor induction of heat shock protein 73 and haem oxygenase was seen after H2O2. Interleukin 1 beta did not induce heat shock proteins in rat thyroid cells, rat mesangial cells or in human monocytes. Tumour necrosis factor alpha did not induce selective protein synthesis. Pre-exposure of islets to heat, tumour necrosis factor alpha, or H2O2 did not prevent the impairment of glucose-stimulated insulin release seen after 24 h of interleukin 1 beta exposure. The data are compatible with free radical induction by interleukin 1 beta. However, the heat shock response is not specific for oxidative injury, and previous studies have shown discrepant effects as to a protective effect of free radical scavengers against interleukin 1 beta-mediated beta-cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
Helqvist
S
S
Steno Memorial Hospital, Gentofte, Denmark.
Polla
B S
BS
Johannesen
J
J
Nerup
J
J
D000818:Animals; D001345:Autoradiography; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D006358:Hot Temperature; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008715:Methionine / Q000378:metabolism; D008970:Molecular Weight; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology*; D013462:Sulfur Radioisotopes; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D006360:Heat-Shock Proteins; D007328:Insulin; D007375:Interleukin-1; D011994:Recombinant Proteins; D013462:Sulfur Radioisotopes; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D008715:Methionine; D006861:Hydrogen Peroxide