Apoptosis signal-regulating kinase 1/p38 signaling pathway negatively regulates physiological hypertrophy. Export

@article{citeulike:5785006, abstract = {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.}, author = {Taniike, Masayuki and Yamaguchi, Osamu and Tsujimoto, Ikuko and Hikoso, Shungo and Takeda, Toshihiro and Nakai, Atsuko and Omiya, Shigemiki and Mizote, Isamu and Nakano, Yuko and Higuchi, Yoshiharu and Matsumura, Yasushi and Nishida, Kazuhiko and Ichijo, Hidenori and Hori, Masatsugu and Otsu, Kinya}, citeulike-article-id = {5785006}, citeulike-linkout-0 = {http://dx.doi.org/10.1161/CIRCULATIONAHA.107.710434}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18195174}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18195174}, day = {29}, doi = {10.1161/CIRCULATIONAHA.107.710434}, issn = {1524-4539}, journal = {Circulation}, keywords = {ask, cv, hypertrophy, p38}, month = {January}, number = {4}, pages = {545--552}, posted-at = {2009-09-15 04:40:19}, priority = {2}, title = {Apoptosis signal-regulating kinase 1/p38 signaling pathway negatively regulates physiological hypertrophy.}, url = {http://dx.doi.org/10.1161/CIRCULATIONAHA.107.710434}, volume = {117}, year = {2008} }

TY - JOUR ID - citeulike:5785006 L3 - citeulike-article-id:5785006 N2 - 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. IS - 4 JF - Circulation SN - 1524-4539 EP - 552 TI - Apoptosis signal-regulating kinase 1/p38 signaling pathway negatively regulates physiological hypertrophy. VL - 117 SP - 545 KW - ask KW - cv KW - hypertrophy KW - p38 AU - Taniike, Masayuki AU - Yamaguchi, Osamu AU - Tsujimoto, Ikuko AU - Hikoso, Shungo AU - Takeda, Toshihiro AU - Nakai, Atsuko AU - Omiya, Shigemiki AU - Mizote, Isamu AU - Nakano, Yuko AU - Higuchi, Yoshiharu AU - Matsumura, Yasushi AU - Nishida, Kazuhiko AU - Ichijo, Hidenori AU - Hori, Masatsugu AU - Otsu, Kinya PY - 2008/01/29/ UR - http://dx.doi.org/10.1161/CIRCULATIONAHA.107.710434 ER -