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J Cell Physiol. 2018 Feb;233(2):736-747. doi: 10.1002/jcp.25989. Epub 2017 Jun 7.

Folic acid is necessary for proliferation and differentiation of C2C12 myoblasts.

Author information

1
Department of Pharmacy, College of Pharmacy, Pusan National University, Busan, Republic of Korea.
2
Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
3
Department of Molecular Biology, Pusan National University, Busan, Republic of Korea.
4
Research Center for Anti-Aging Technology Development, Pusan National University, Busan, Republic of Korea.
5
Department of Biochemistry, Pusan National University School of Medicine, Yangsan, Republic of Korea.
6
Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Republic of Korea.

Abstract

Folic acid, a water soluble B vitamin, plays an important role in cellular metabolic activities, such as functioning as a cofactor in one-carbon metabolism for DNA and RNA synthesis as well as nucleotide and amino acid biosynthesis in the body. A lack of dietary folic acid can lead to folic acid deficiency and result in several health problems, including macrocytic anemia, elevated plasma homocysteine, cardiovascular disease, birth defects, carcinogenesis, muscle weakness, and walking difficulty. However, the effect of folic acid deficiency on skeletal muscle development and its molecular mechanisms are unknown. We, therefore, investigated the effect of folic acid deficiency on myogenesis in skeletal muscle cells and found that folic acid deficiency induced proliferation inhibition and cell cycle breaking as well as cellular senescence in C2C12 myoblasts, implying that folic acid deficiency influences skeletal muscle development. Folic acid deficiency also inhibited differentiation of C2C12 myoblasts and induced deregulation of the cell cycle exit and many cell cycle regulatory genes. It inhibited expression of muscle-specific marker MyHC as well as myogenic regulatory factor (myogenin). Moreover, immunocytochemistry and Western blot analyses revealed that DNA damage was more increased in folic acid-deficient medium-treated differentiating C2C12 cells. Furthermore, we found that folic acid resupplementation reverses the effect on the cell cycle and senescence in folic acid-deficient C2C12 myoblasts but does not reverse the differentiation of C2C12 cells. Altogether, the study results suggest that folic acid is necessary for normal development of skeletal muscle cells.

KEYWORDS:

C2C12 muscle cells; DNA damage; folic acid; myogenic differentiation

PMID:
28471487
DOI:
10.1002/jcp.25989
[Indexed for MEDLINE]

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