title: Folic acid promotes the myogenic differentiation of C2C12 murine myoblasts through the Akt signaling pathway.
abstract: Folic acid is a water-soluble vitamin in the B-complex group, and an exogenous intake is required for health, growth and development. As a precursor to co-factors, folic acid is required for one-carbon donors in the synthesis of DNA bases and other essential biomolecules. A lack of dietary folic acid can lead to folic acid deficiency and can therefore result in several health problems, including macrocytic anemia, elevated plasma homocysteine levels, cardiovascular disease, birth defects, carcinogenesis, muscle weakness and difficulty in walking. Previous studies have indicated that folic acid exerts a positive effect on skeletal muscle functions. However, the precise role of folic acid in skeletal muscle cell differentiation remains poorly understood. Thus, in the present study, we examined the effects of folic acid on neo-myotube maturation and differentiation using C2C12 murine myoblasts. We found that folic acid promoted the formation of multinucleated myotubes, and increased the fusion index and creatine kinase (CK) activity in a concentration-dependent manner. In addition, western blot analysis revealed that the expression levels of the muscle-specific marker, myosin heavy chain (MyHC), as well as those of the myogenic regulatory factors (MRFs), MyoD and myogenin, were increased in the folic acid-treated myotubes during myogenic differentiation. Folic acid also promoted the activation of the Akt pathway, and this effect was inhibited by treatment of the C2C12 cells with LY294002 (Akt inhibitor). Blocking of the Akt pathway with a specific inhibitor revealed that it was necessary for mediating the stimulatory effects of folic acid on muscle cell differentiation and fusion. Taken together, our data suggest that folic acid promotes the differentiation of C2C12 cells through the activation of the Akt pathway.
authors: Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors: Seong Yeon
authors: SY
authors: Hwang
authors: Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors: Yong Jung
authors: YJ
authors: Kang
authors: Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors: Bokyung
authors: B
authors: Sung
authors: Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors: Minjung
authors: M
authors: Kim
authors: Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors: Dong Hwan
authors: DH
authors: Kim
authors: Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors: Yujin
authors: Y
authors: Lee
authors: Department of Molecular Biology, Pusan National University, Busan 609-735, Republic of Korea.
authors: Mi-Ae
authors: MA
authors: Yoo
authors: Research Center for Anti-Aging Technology Development, Pusan National University, Busan 609-735, Republic of Korea.
authors: Cheol Min
authors: CM
authors: Kim
authors: Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors: Hae Young
authors: HY
authors: Chung
authors: Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors: Nam Deuk
authors: ND
authors: Kim
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D005492:Folic Acid / Q000494:pharmacology*; D051379:Mice; D024510:Muscle Development / Q000187:drug effects*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D005492:Folic Acid; D051057:Proto-Oncogene Proteins c-akt