Heat shock protects PC12 cells against MPP+ toxicity.
A mild heat shock preconditioning has been shown to induce thermotolerance and protection against a number of cytotoxic agents that may induce cell death by either apoptosis or necrosis. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that selectively targets dopaminergic cells of the substantia nigra and, as such, it is often used to induce neuronal cell death in models of Parkinson's disease. PC12 cells were heat-shocked for 1 h at 41.5 degrees C. This led to a rapid induction of Hsp25 and Hsp70. Levels of these proteins remained elevated for at least 24 h post heat shock. Treatment of PC12 cells with 1-methyl-4-phenylpyridinium (MPP(+)), the active metabolite of MPTP, resulted in cell death. Morphological analysis and the lack of caspase activity suggested that cell death was by necrosis. Heat shocking the cells 6 h prior to addition of MPP(+) significantly inhibited the induction of cell death by MPP(+). These results indicated that heat shock is protective against MPP(+) neurotoxicity in PC12 cells.
Quigney
Declan J
DJ
Cell Stress and Apoptosis Research Group, Department of Biochemistry and the National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland.
Gorman
Adrienne M
AM
Samali
Afshin
A
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D016923:Cell Death; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins; D006358:Hot Temperature; D020267:MPTP Poisoning; D009363:Neoplasm Proteins / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D016716:PC12 Cells / Q000187:drug effects*; D051381:Rats; D012769:Shock; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
D003374:Coumarins; D005456:Fluorescent Dyes; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D009363:Neoplasm Proteins; D009842:Oligopeptides; D013778:Tetrazolium Salts; D013844:Thiazoles; C102580:acetyl-aspartyl-glutamyl-valyl-aspartyl-amino-4-methylcoumarin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C022616:thiazolyl blue