Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10770108 | Biochemical and Biophysical Research Communications | 2005 | 6 Pages |
Abstract
The molecular basis of myocardial cell death in the ischemia-reperfused heart still remains to be clarified. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays an important role in stress-induced apoptosis. We studied ASK1â/â mice to examine the role of ASK1 in ischemia-reperfusion injury. In the wild-type heart, ischemia-reperfusion resulted in necrotic injury, whereas infarct size was drastically reduced in the ASK1â/â heart. The necrotic injury was not accompanied with any evidence of apoptosis such as an increase in TUNEL-positive cells, DNA fragmentation or the activation of caspase-3. ASK1â/â cardiomyocytes were more resistant to H2O2- or Ca2+-induced apoptotic and non-apoptotic cell death compared with wild-type cells. These data suggest that ASK1 is involved in necrosis as well as apoptosis and that ASK1-dependent necrosis is likely to contribute to myocardial cell death in the ischemia-reperfused heart.
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Authors
Tetsuya Watanabe, Kinya Otsu, Toshihiro Takeda, Osamu Yamaguchi, Shungo Hikoso, Kazunori Kashiwase, Yoshiharu Higuchi, Masayuki Taniike, Atsuko Nakai, Yasushi Matsumura, Kazuhiko Nishida, Hidenori Ichijo, Masatsugu Hori,