Folic acid is necessary for proliferation and differentiation of C2C12 myoblasts
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 def...
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| Veröffentlicht in: | Journal of cellular physiology 2018-02, Vol.233 (2), p.736-747 |
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| creator | Hwang, Seong Y. Kang, Yong J. Sung, Bokyung Jang, Jung Y. Hwang, Na L. Oh, Hye J. Ahn, Yu R. Kim, Hong J. Shin, Jin H. Yoo, Mi‐ae Kim, Cheol M. Chung, Hae Y. Kim, Nam D. |
| description | 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.
Effect of folic acid resupplementation on the differentiation of C2C12 cells cultured in folic acid‐deficient conditions. 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. |
| doi_str_mv | 10.1002/jcp.25989 |
| format | Article |
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Effect of folic acid resupplementation on the differentiation of C2C12 cells cultured in folic acid‐deficient conditions. 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.</description><identifier>ISSN: 0021-9541</identifier><identifier>EISSN: 1097-4652</identifier><identifier>DOI: 10.1002/jcp.25989</identifier><identifier>PMID: 28471487</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Amino acids ; Anemia ; Animals ; Biosynthesis ; Birth defects ; C2C12 muscle cells ; Carcinogenesis ; Carcinogens ; Cardiovascular diseases ; Cell cycle ; Cell Cycle - drug effects ; Cell Differentiation - drug effects ; Cell Line ; Cell proliferation ; Cell Proliferation - drug effects ; Cellular Senescence - drug effects ; Congenital defects ; Deoxyribonucleic acid ; Deregulation ; Differentiation ; DNA ; DNA biosynthesis ; DNA Damage ; Folic acid ; Folic Acid - pharmacology ; Folic Acid Deficiency - drug therapy ; Folic Acid Deficiency - metabolism ; Folic Acid Deficiency - pathology ; Gene expression ; Health problems ; Homocysteine ; Immunocytochemistry ; Metabolism ; Mice ; Molecular modelling ; Muscle Development - drug effects ; Musculoskeletal system ; Myoblasts ; Myoblasts, Skeletal - drug effects ; Myoblasts, Skeletal - metabolism ; Myoblasts, Skeletal - pathology ; Myogenesis ; myogenic differentiation ; Myogenin ; Myogenin - metabolism ; Myosin Heavy Chains - metabolism ; Ribonucleic acid ; RNA ; Senescence ; Skeletal muscle ; Time Factors ; Transcription ; Vitamin B ; Vitamin deficiency ; Walking</subject><ispartof>Journal of cellular physiology, 2018-02, Vol.233 (2), p.736-747</ispartof><rights>2017 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4199-3a5fd9684fc5f9fe728ec2921f644760aff24d58f871d58faa28753f2392457d3</citedby><cites>FETCH-LOGICAL-c4199-3a5fd9684fc5f9fe728ec2921f644760aff24d58f871d58faa28753f2392457d3</cites><orcidid>0000-0001-9033-9865</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcp.25989$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcp.25989$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28471487$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hwang, Seong Y.</creatorcontrib><creatorcontrib>Kang, Yong J.</creatorcontrib><creatorcontrib>Sung, Bokyung</creatorcontrib><creatorcontrib>Jang, Jung Y.</creatorcontrib><creatorcontrib>Hwang, Na L.</creatorcontrib><creatorcontrib>Oh, Hye J.</creatorcontrib><creatorcontrib>Ahn, Yu R.</creatorcontrib><creatorcontrib>Kim, Hong J.</creatorcontrib><creatorcontrib>Shin, Jin H.</creatorcontrib><creatorcontrib>Yoo, Mi‐ae</creatorcontrib><creatorcontrib>Kim, Cheol M.</creatorcontrib><creatorcontrib>Chung, Hae Y.</creatorcontrib><creatorcontrib>Kim, Nam D.</creatorcontrib><title>Folic acid is necessary for proliferation and differentiation of C2C12 myoblasts</title><title>Journal of cellular physiology</title><addtitle>J Cell Physiol</addtitle><description>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.
Effect of folic acid resupplementation on the differentiation of C2C12 cells cultured in folic acid‐deficient conditions. 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.</description><subject>Amino acids</subject><subject>Anemia</subject><subject>Animals</subject><subject>Biosynthesis</subject><subject>Birth defects</subject><subject>C2C12 muscle cells</subject><subject>Carcinogenesis</subject><subject>Carcinogens</subject><subject>Cardiovascular diseases</subject><subject>Cell cycle</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Line</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Cellular Senescence - drug effects</subject><subject>Congenital defects</subject><subject>Deoxyribonucleic acid</subject><subject>Deregulation</subject><subject>Differentiation</subject><subject>DNA</subject><subject>DNA biosynthesis</subject><subject>DNA Damage</subject><subject>Folic acid</subject><subject>Folic Acid - pharmacology</subject><subject>Folic Acid Deficiency - drug therapy</subject><subject>Folic Acid Deficiency - metabolism</subject><subject>Folic Acid Deficiency - pathology</subject><subject>Gene expression</subject><subject>Health problems</subject><subject>Homocysteine</subject><subject>Immunocytochemistry</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Molecular modelling</subject><subject>Muscle Development - drug effects</subject><subject>Musculoskeletal system</subject><subject>Myoblasts</subject><subject>Myoblasts, Skeletal - drug effects</subject><subject>Myoblasts, Skeletal - metabolism</subject><subject>Myoblasts, Skeletal - pathology</subject><subject>Myogenesis</subject><subject>myogenic differentiation</subject><subject>Myogenin</subject><subject>Myogenin - metabolism</subject><subject>Myosin Heavy Chains - metabolism</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Senescence</subject><subject>Skeletal muscle</subject><subject>Time Factors</subject><subject>Transcription</subject><subject>Vitamin B</subject><subject>Vitamin deficiency</subject><subject>Walking</subject><issn>0021-9541</issn><issn>1097-4652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE9LAzEQxYMotlYPfgEJePKwbTKbbJKjLNY_FOxBzyHNJpDS7tZki_Tbm7rqzdMw8368mXkIXVMypYTAbG13U-BKqhM0pkSJglUcTtE4a7RQnNERukhpTQhRqizP0QgkE5RJMUbLebcJFhsbGhwSbp11KZl4wL6LeBez6F00fehabNoGN8Hn3rV9GGadxzXUFPD20K02JvXpEp15s0nu6qdO0Pv84a1-Khavj8_1_aKwjCpVlIb7RlWSecu98k6AdBYUUF8xJipivAfWcOmloMdiDEjBSw-lAsZFU07Q7eCbj_zYu9TrdbePbV6pqaoIkwoAMnU3UDZ2KUXn9S6Gbf5PU6KP2emcnf7OLrM3P4771dY1f-RvWBmYDcBn2LjD_076pV4Oll8TwXdR</recordid><startdate>201802</startdate><enddate>201802</enddate><creator>Hwang, Seong Y.</creator><creator>Kang, Yong J.</creator><creator>Sung, Bokyung</creator><creator>Jang, Jung Y.</creator><creator>Hwang, Na L.</creator><creator>Oh, Hye J.</creator><creator>Ahn, Yu R.</creator><creator>Kim, Hong J.</creator><creator>Shin, Jin H.</creator><creator>Yoo, Mi‐ae</creator><creator>Kim, Cheol M.</creator><creator>Chung, Hae Y.</creator><creator>Kim, Nam D.</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><orcidid>https://orcid.org/0000-0001-9033-9865</orcidid></search><sort><creationdate>201802</creationdate><title>Folic acid is necessary for proliferation and differentiation of C2C12 myoblasts</title><author>Hwang, Seong Y. ; Kang, Yong J. ; Sung, Bokyung ; Jang, Jung Y. ; Hwang, Na L. ; Oh, Hye J. ; Ahn, Yu R. ; Kim, Hong J. ; Shin, Jin H. ; Yoo, Mi‐ae ; Kim, Cheol M. ; Chung, Hae Y. ; Kim, Nam D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4199-3a5fd9684fc5f9fe728ec2921f644760aff24d58f871d58faa28753f2392457d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Amino acids</topic><topic>Anemia</topic><topic>Animals</topic><topic>Biosynthesis</topic><topic>Birth defects</topic><topic>C2C12 muscle cells</topic><topic>Carcinogenesis</topic><topic>Carcinogens</topic><topic>Cardiovascular diseases</topic><topic>Cell cycle</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Line</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Cellular Senescence - drug effects</topic><topic>Congenital defects</topic><topic>Deoxyribonucleic acid</topic><topic>Deregulation</topic><topic>Differentiation</topic><topic>DNA</topic><topic>DNA biosynthesis</topic><topic>DNA Damage</topic><topic>Folic acid</topic><topic>Folic Acid - pharmacology</topic><topic>Folic Acid Deficiency - drug therapy</topic><topic>Folic Acid Deficiency - metabolism</topic><topic>Folic Acid Deficiency - pathology</topic><topic>Gene expression</topic><topic>Health problems</topic><topic>Homocysteine</topic><topic>Immunocytochemistry</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Molecular modelling</topic><topic>Muscle Development - drug effects</topic><topic>Musculoskeletal system</topic><topic>Myoblasts</topic><topic>Myoblasts, Skeletal - drug effects</topic><topic>Myoblasts, Skeletal - metabolism</topic><topic>Myoblasts, Skeletal - pathology</topic><topic>Myogenesis</topic><topic>myogenic differentiation</topic><topic>Myogenin</topic><topic>Myogenin - metabolism</topic><topic>Myosin Heavy Chains - metabolism</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Senescence</topic><topic>Skeletal muscle</topic><topic>Time Factors</topic><topic>Transcription</topic><topic>Vitamin B</topic><topic>Vitamin deficiency</topic><topic>Walking</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hwang, Seong Y.</creatorcontrib><creatorcontrib>Kang, Yong J.</creatorcontrib><creatorcontrib>Sung, Bokyung</creatorcontrib><creatorcontrib>Jang, Jung Y.</creatorcontrib><creatorcontrib>Hwang, Na L.</creatorcontrib><creatorcontrib>Oh, Hye J.</creatorcontrib><creatorcontrib>Ahn, Yu R.</creatorcontrib><creatorcontrib>Kim, Hong J.</creatorcontrib><creatorcontrib>Shin, Jin H.</creatorcontrib><creatorcontrib>Yoo, Mi‐ae</creatorcontrib><creatorcontrib>Kim, Cheol M.</creatorcontrib><creatorcontrib>Chung, Hae Y.</creatorcontrib><creatorcontrib>Kim, Nam D.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Journal of cellular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hwang, Seong Y.</au><au>Kang, Yong J.</au><au>Sung, Bokyung</au><au>Jang, Jung Y.</au><au>Hwang, Na L.</au><au>Oh, Hye J.</au><au>Ahn, Yu R.</au><au>Kim, Hong J.</au><au>Shin, Jin H.</au><au>Yoo, Mi‐ae</au><au>Kim, Cheol M.</au><au>Chung, Hae Y.</au><au>Kim, Nam D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Folic acid is necessary for proliferation and differentiation of C2C12 myoblasts</atitle><jtitle>Journal of cellular physiology</jtitle><addtitle>J Cell Physiol</addtitle><date>2018-02</date><risdate>2018</risdate><volume>233</volume><issue>2</issue><spage>736</spage><epage>747</epage><pages>736-747</pages><issn>0021-9541</issn><eissn>1097-4652</eissn><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.
Effect of folic acid resupplementation on the differentiation of C2C12 cells cultured in folic acid‐deficient conditions. 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.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28471487</pmid><doi>10.1002/jcp.25989</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-9033-9865</orcidid></addata></record> |
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| subjects | Amino acids Anemia Animals Biosynthesis Birth defects C2C12 muscle cells Carcinogenesis Carcinogens Cardiovascular diseases Cell cycle Cell Cycle - drug effects Cell Differentiation - drug effects Cell Line Cell proliferation Cell Proliferation - drug effects Cellular Senescence - drug effects Congenital defects Deoxyribonucleic acid Deregulation Differentiation DNA DNA biosynthesis DNA Damage Folic acid Folic Acid - pharmacology Folic Acid Deficiency - drug therapy Folic Acid Deficiency - metabolism Folic Acid Deficiency - pathology Gene expression Health problems Homocysteine Immunocytochemistry Metabolism Mice Molecular modelling Muscle Development - drug effects Musculoskeletal system Myoblasts Myoblasts, Skeletal - drug effects Myoblasts, Skeletal - metabolism Myoblasts, Skeletal - pathology Myogenesis myogenic differentiation Myogenin Myogenin - metabolism Myosin Heavy Chains - metabolism Ribonucleic acid RNA Senescence Skeletal muscle Time Factors Transcription Vitamin B Vitamin deficiency Walking |
| title | Folic acid is necessary for proliferation and differentiation of C2C12 myoblasts |
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