title: Disruption of a single copy of the p38alpha MAP kinase gene leads to cardioprotection against ischemia-reperfusion.
abstract: The p38 mitogen-activated protein kinase (p38) is activated in the heart during ischemia-reperfusion. However, it is not clear whether the activation of p38 is the protective response or the kinase mediates the cellular damage by ischemia-reperfusion. We examined the role of p38alpha in ischemia-reperfusion injury by studying p38alpha(+/-) mice. The p38alpha protein level in the p38alpha(+/-) heart was 50+/-8.7% compared with that in the p38alpha(+/+) heart. Upon reperfusion following ischemia for 25min, p38alpha activity was transiently increased. The maximum level of p38 activity in p38alpha(+/-) was 60+/-10.5% compared with that in p38alpha(+/+). In the p38alpha(+/+) heart, 25min ischemia and 2h reperfusion resulted in necrotic injury (37.1+/-2.7% of the area at risk), whereas infarct size was drastically reduced to 7.2+/-0.7% in the p38alpha(+/-) heart. These suggested that p38alpha plays a pivotal role in the signal transduction pathway mediating myocardial cell death caused by ischemia-reperfusion.
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. kotsu@medone.med.osaka-u.ac.jp
authors.forename: Kinya
authors.initials: K
authors.lastname: Otsu
authors.forename: Nobushige
authors.initials: N
authors.lastname: Yamashita
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nishida
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirotani
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamaguchi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Watanabe
authors.forename: Shungo
authors.initials: S
authors.lastname: Hikoso
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Higuchi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Masumi
authors.initials: M
authors.lastname: Maruyama
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Sudo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osada
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
mesh_terms: D000818:Animals; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017202:Myocardial Ischemia / Q000201:enzymology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases