Hypothermia enhances heat-shock protein 70 production in ischemic brains.
Although moderate hypothermia is one of the most robust and effective techniques available for reducing ischemic injury, its key mechanism still remains unclear. Our proteomic analysis of the brains of rats treated with a 2-h middle cerebral artery occlusion showed that postischemic hypothermia markedly potentiated a sustained increase in heat-shock protein 70 (Hsp70). The elevated Hsp70 level was confirmed by enzyme-linked immunosorbent assay, western blot analysis, and immunohistochemical staining. Expression of other Hsp proteins was unaffected by hypothermia. Interestingly, hypothermia did not increased, even decreased, the upregulation of hsp70 mRNA expression by ischemia, suggesting that Hsp70 abundance is controlled by an unknown posttranscriptional regulation. As Hsp70 exerts a protective role against ischemic damage, the specific increase in Hsp70 production may contribute to the neuroprotective effect of hypothermia.
Pharmacology Research Laboratories III, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Osaka, Japan.
Yasuko
Y
Terao
Saku
S
Miyamoto
Kazuko
K
Hirai
Hidenori
H
Kamiguchi
Hiroyuki
H
Ohta
Masato
M
Shimojo
Yoshihiro
Y
Kiyota
Satoru
S
Asahi
Yasufumi
Y
Sakura
Yasushi
Y
Shintani
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001831:Body Temperature / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D020520:Brain Infarction / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy*; D002470:Cell Survival / Q000502:physiology; D019610:Cytoprotection / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000502:physiology
D015415:Biomarkers; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger