title: Apoptosis signal-regulating kinase 1 is an intracellular inducer of p38 MAPK-mediated myogenic signalling in cardiac myoblasts.
abstract: Myogenic differentiation is an essential process for the myogenesis in response to various extracellular stimuli. p38 MAPK is a core signalling molecule in myogenic differentiation. The activation of p38 MAPK is required for myogenic differentiation; however, the mechanism for this activation remains undefined. ASK1 is a member of the MAP3K family that activates both JNK and p38 MAPK pathways in response to an array of stresses such as oxidative stress, endoplasmic reticulum stress and calcium influx. Here, we reported that TNFα was significantly released from H9c2 cardiac myoblast in differentiation medium. Furthermore, the oxidant H(2)O(2) acted as a messenger in the TNFα signalling pathway to disrupt the complex of ASK1-Trx, which was followed by the activation of ASK1 in cardiac myogenic differentiation. Subsequently, the activated ASK1 stimulated MKK3/6-p38MAPK signalling cascade to induce specific myogenic differentiation. In addition, exogenous TNFα added to the medium at physiological levels enhanced the ASK1-p38 MAPK signalling pathway through the increased generation of H(2)O(2). Interestingly, inhibition of p38 MAPK abrogated the production of H(2)O(2), suggesting that there might be a positive feedback loop in the myogenic-redox signalling pathway. These results indicate that ASK1 is a new intracellular regulator of activation of the p38 MAPK in cardiac myogenic differentiation.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical Research Center for Bioreaction to Reactive OxygenSpecies and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Tae Gyu
authors.initials: TG
authors.lastname: Choi
authors.forename: Jisun
authors.initials: J
authors.lastname: Lee
authors.forename: Joohun
authors.initials: J
authors.lastname: Ha
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kim
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D025461:Feedback, Physiological; D006861:Hydrogen Peroxide / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D024510:Muscle Development / Q000187:drug effects / Q000502:physiology; D032386:Myoblasts, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013879:Thioredoxins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013879:Thioredoxins; D006861:Hydrogen Peroxide; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5