Role of heat shock proteins in MPTP-induced neurotoxicity.
1. MPTP and its major metabolite MPP+ have significant effects on body temperature regulation in mice, which are both age and strain dependent. 2. These effects were produced by intraperitoneal injection of either MPTP or MPP+ suggesting that the predominant site of action lies outside the blood-brain barrier. 3. The initial hyperthermia induced in CD-1 mice, which was sufficient to lead to the induction of HSP 72, appears to have a protective effect with regard to striatal dopamine depletion. 4. Cultured CHO cells are sensitive to MPP+ cytotoxicity at high concentrations. This toxicity can be reduced by heat shocking the cells prior to the addition of MPP(+)-containing media. 5. In summary, these in vivo and in vitro data strongly suggest that heat shock proteins (HSP 72) play a neuroprotective role in MPTP-induced neurotoxicity.
Freyaldenhoven
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Neurochemistry Laboratory, National Center for Toxicological Research/FDA, Jefferson, Arkansas 72079-9502, USA.
Ali
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D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D016466:CHO Cells; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D006224:Cricetinae; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D007770:L-Lactate Dehydrogenase; D020267:MPTP Poisoning; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009498:Neurotoxins / Q000633:toxicity*; D013997:Time Factors
D015259:Dopamine Agents; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D009498:Neurotoxins; D007770:L-Lactate Dehydrogenase; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine