title: Tetrahydropalmatine promotes myoblast differentiation through activation of p38MAPK and MyoD.
abstract: Myoblast differentiation is fundamental to the development and regeneration of skeletal muscle after injury or disease. MyoD family transcription factors play a key role to promote myoblast differentiation. In a screen for MyoD activators, we identified tetrahydropalmatine (THP), a natural compound isolated from Corydalis turtschaninovii. The treatment of C2C12 myoblasts with THP enhanced the level of MyoD, Myogenin and myosin heavy chain (MHC) proteins and the formation of larger multinucleated myotubes, compared to the control treatment. The THP treatment dramatically enhanced the activities of p38MAPK and Akt, the key promyogenic kinases which activate MyoD. The enhanced myoblast differentiation by THP treatment can be blocked by inhibition of p38MAPK or Akt by SB203580 or LY294002, respectively. In addition, THP treatment restored myotube formation of Cdo-depleted C2C12 cells through activation of p38MAPK. Moreover, THP enhanced the efficiency of trans-differentiation of 10T1/2 fibroblasts into myoblasts mediated by MyoD. These results indicate that THP has a promyogenic effect by upregulation of p38MAPK and Akt resulting in enhanced MyoD activation. Our findings suggest that THP has a potential as a therapeutic candidate to prevent fibrosis and improve muscle regeneration and repair.
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Sang-Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Miran
authors.initials: M
authors.lastname: Yoo
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Ga-Yeon
authors.initials: GY
authors.lastname: Go
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Jeongmi
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Gyeonwoo Korean Medical Center, Seoul 121-758, Republic of Korea.
authors.forename: Hyo-Gun
authors.initials: HG
authors.lastname: Lee
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Yong-Kee
authors.initials: YK
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Seo
authors.affiliation: The Graduate School of Biotechnology, Institute of Life Sciences & Resources, Kyung Hee University, Yongin 446-701, Republic of Korea.
authors.forename: Nam-In
authors.initials: NI
authors.lastname: Baek
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Jae-Ha
authors.initials: JH
authors.lastname: Ryu
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 440-746, Republic of Korea. Electronic address: jskang@skku.ac.kr.
authors.forename: Jong-Sun
authors.initials: JS
authors.lastname: Kang
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea. Electronic address: gbae@sookmyung.ac.kr.
authors.forename: Gyu-Un
authors.initials: GU
authors.lastname: Bae
mesh_terms: D000818:Animals; D001600:Berberine Alkaloids / Q000737:chemistry*; D002450:Cell Communication; D002454:Cell Differentiation / Q000187:drug effects*; D002867:Chromones / Q000737:chemistry; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology; D005355:Fibrosis / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D007093:Imidazoles / Q000737:chemistry; D051379:Mice; D009025:Morpholines / Q000737:chemistry; D017570:MyoD Protein / Q000378:metabolism*; D032446:Myoblasts / Q000187:drug effects* / Q000378:metabolism; D018008:Myogenin / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry; D012038:Regeneration; D055948:Sarcopenia / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D001600:Berberine Alkaloids; D002867:Chromones; D007093:Imidazoles; D009025:Morpholines; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D018008:Myogenin; D011725:Pyridines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C014215:tetrahydropalmatine; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
keywords: Corydalis turtschaninovii; MyoD; Myoblast differentiation; Sarcopenia; Tetrahydropalmatine; p38MAPK