Heat shock transcription factor 1 protects cardiomyocytes from ischemia/reperfusion injury.
BACKGROUND
Because cardiomyocyte death causes heart failure, it is important to find the molecules that protect cardiomyocytes from death. The death trap is a useful method to identify cell-protective genes.


RESULTS
In this study, we isolated the heat shock transcription factor 1 (HSF1) as a protective molecule by the death trap method. Cell death induced by hydrogen peroxide was prevented by overexpression of HSF1 in COS7 cells. Thermal preconditioning at 42 degrees C for 60 minutes activated HSF1, which played a critical role in survival of cardiomyocytes from oxidative stress. In the heart of transgenic mice overexpressing a constitutively active form of HSF1, ischemia followed by reperfusion-induced ST-segment elevation in ECG was recovered faster, infarct size was smaller, and cardiomyocyte death was less than wild-type mice. Protein kinase B/Akt was more strongly activated, whereas Jun N-terminal kinase and caspase 3 were less activated in transgenic hearts than wild-type ones.


CONCLUSIONS
These results suggest that HSF1 protects cardiomyocytes from death at least in part through activation of Akt and inactivation of Jun N-terminal kinase and caspase 3.
Zou
Yunzeng
Y
Department of Cardiovascular Science and Medicine, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. komuro-tky@umin.ac.jp
Zhu
Weidong
W
Sakamoto
Masaya
M
Qin
Yingjie
Y
Akazawa
Hiroshi
H
Toko
Haruhiro
H
Mizukami
Miho
M
Takeda
Norihiko
N
Minamino
Tohru
T
Takano
Hiroyuki
H
Nagai
Toshio
T
Nakai
Akira
A
Komuro
Issei
I
D000818:Animals; D017209:Apoptosis; D019556:COS Cells; D002470:Cell Survival; D002478:Cells, Cultured; D003001:Cloning, Molecular; D019610:Cytoprotection; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004562:Electrocardiography; D000076249:Heat Shock Transcription Factors; D051379:Mice; D008822:Mice, Transgenic; D015428:Myocardial Reperfusion Injury / Q000175:diagnosis / Q000201:enzymology / Q000473:pathology*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000201:enzymology / Q000473:pathology*; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; C000619709:Hsf1 protein, rat; D014157:Transcription Factors; D011494:Protein Kinases