Apoptosis Signal-Regulating Kinase 1/p38 Signaling Pathway Negatively Regulates Physiological Hypertrophy.

Apoptosis Signal-Regulating Kinase 1/p38 Signaling Pathway Negatively Regulates Physiological Hypertrophy. Research Abstract Details 

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Apoptosis Signal-Regulating Kinase 1/p38 Signaling Pathway Negatively Regulates Physiological Hypertrophy. Abstract Text:

Masayuki Taniike,Osamu Yamaguchi,Ikuko Tsujimoto,Shungo Hikoso,Toshihiro Takeda,Atsuko Nakai,Shigemiki Omiya,Isamu Mizote,Yuko Nakano,Yoshiharu Higuchi,Yasushi Matsumura,Kazuhiko Nishida,Hidenori Ichijo,Masatsugu Hori,Kinya Otsu,Masayuki Taniike,Osamu Yamaguchi,Ikuko Tsujimoto,Shungo Hikoso,Toshihiro Takeda,Atsuko Nakai,Shigemiki Omiya,Isamu Mizote,Yuko Nakano,Yoshiharu Higuchi,Yasushi Matsumura,Kazuhiko Nishida,Hidenori Ichijo,Masatsugu Hori,Kinya Otsu,Masayuki Taniike,Osamu Yamaguchi,Ikuko Tsujimoto,Shungo Hikoso,Toshihiro Takeda,Atsuko Nakai,Shigemiki Omiya,Isamu Mizote,Yuko Nakano,Yoshiharu Higuchi,Yasushi Matsumura,Kazuhiko Nishida,Hidenori Ichijo,Masatsugu Hori,Kinya Otsu,

BACKGROUND: Mechanical stress on the heart can lead to crucially different outcomes. Physiological stimuli such as exercise cause adaptive cardiac hypertrophy, characterized by a normal cardiac structure and normal or enhanced cardiac function. Pathological stimuli such as hypertension and aortic valvular stenosis cause maladaptive cardiac remodeling and ultimately heart failure. Apoptosis signal-regulating kinase 1 (ASK1) is known to be involved in pathological cardiac remodeling, but it has not been determined whether ASK1 pathways coordinate the signaling cascade leading to physiological type cardiac growth. METHODS AND RESULTS: To evaluate the role of ASK1 in the physiological form of cardiac growth, mice lacking ASK1 (ASK1(-/-)) were exercised by swimming for 4 weeks. ASK1(-/-) mice showed exaggerated growth of the heart accompanied by typical characteristics of physiological hypertrophy. Their swimming-induced activation of Akt, a key molecule in the signaling cascade of physiological hypertrophy, increased more than that seen in wild-type controls. The activation of p38, a downstream kinase of ASK1, was suppressed selectively in the swimming-exercised ASK1(-/-) mice. Furthermore, the inhibition of ASK1 or p38 activity enhanced insulin-like growth factor 1-induced protein synthesis in rat neonatal ventricular cardiomyocytes, and the treatment with a specific inhibitor of p38 resulted in enhancement of Akt activation and suppression of protein phosphatase 2A activation. The cardiac-specific p38alpha-deficient mice developed an exacerbated form of cardiac hypertrophy in response to swimming exercise. CONCLUSIONS: These results indicate that the ASK1/p38 signaling pathway negatively regulates physiological hypertrophy.

Apoptosis Signal-Regulating Kinase 1/p38 Signaling Pathway Negatively Regulates Physiological Hypertrophy. Publishing Authors By Initials

M Taniike,O Yamaguchi,I Tsujimoto,S Hikoso,T Takeda,A Nakai,S Omiya,I Mizote,Y Nakano,Y Higuchi,Y Matsumura,K Nishida,H Ichijo,M Hori,K Otsu,M Taniike,O Yamaguchi,I Tsujimoto,S Hikoso,T Takeda,A Nakai,S Omiya,I Mizote,Y Nakano,Y Higuchi,Y Matsumura,K Nishida,H Ichijo,M Hori,K Otsu,M Taniike,O Yamaguchi,I Tsujimoto,S Hikoso,T Takeda,A Nakai,S Omiya,I Mizote,Y Nakano,Y Higuchi,Y Matsumura,K Nishida,H Ichijo,M Hori,K Otsu,

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Apoptosis Signal-Regulating Kinase 1/p38 Signaling Pathway Negatively Regulates Physiological Hypertrophy. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Circulation

VOLUME: 117

Page Numbers: 545-52

Journal Abbreviation: Circulation

ISSN: 1524-4539

DAY: 14

MONTH: 01

YEAR: 2008

Apoptosis Signal-Regulating Kinase 1/p38 Signaling Pathway Negatively Regulates Physiological Hypertrophy. Information

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LANGUAGE: eng

NlmUniqueID: 147763

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AFFILIATION: 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. kotsu@medone.med.osaka-u.ac.jp.

Country: United States

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MEDLINETA: Circulation

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