title: Apoptosis signal-regulating kinase 1 is involved not only in apoptosis but also in non-apoptotic cardiomyocyte death.
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 ASK1(-/-) 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 ASK1(-/-) 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. ASK1(-/-) cardiomyocytes were more resistant to H(2)O(2)- or Ca(2+)-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.
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Watanabe
authors.forename: Kinya
authors.initials: K
authors.lastname: Otsu
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Takeda
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamaguchi
authors.forename: Shungo
authors.initials: S
authors.lastname: Hikoso
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kashiwase
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Higuchi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Taniike
authors.forename: Atsuko
authors.initials: A
authors.lastname: Nakai
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nishida
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ichijo
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D048848:MAP Kinase Kinase Kinase 5 / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000201:enzymology* / Q000473:pathology*; D009336:Necrosis; D015427:Reperfusion Injury / Q000201:enzymology* / Q000473:pathology*
chemical_list: D048848:MAP Kinase Kinase Kinase 5