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      식이성 폴리페놀 (-)-epigallocatechin-3-gallate가 mouse C2C12 myoblast 분화에 미치는 영향 = Effects of dietary polyphenol (-)-epigallocatechin-3-gallate on the differentiation of mouse C2C12 myoblasts

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      https://www.riss.kr/link?id=A103756223

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      다국어 초록 (Multilingual Abstract)

      In the present investigation, we studied the modulating effects of (-)-epigallocatechin-3-gallate(EGCG) on the differentiation of mouse C2C12 myoblasts. We found that the strong inhibitory effect of EGCG on DNA methyltransferase-mediated DNA methylation induced transdifferentiation of C2C12 myoblasts into smooth muscle cells demonstrated by both morphological changes and immunofluorescent staining. C2C12 myoblasts treated with EGCG for 4 days expressed smooth muscle ${\alpha}-actin$ protein. Real-time PCR data revealed that smooth muscle ${\alpha}-actin$ mRNA was induced by EGCG treated C2C12 myoblasts in a concentration-dependent manner. Smooth muscle ${\alpha}-actin$ mRNA concentration increased 330% and 490% after 2 and 3 days of 50 ${\mu}M$ of EGCG treatment. The expression of another smooth muscle marker, transgelin, mRNA was also increased up to 9-fold by 4 days of EGCG treatment compared with control in a concentration-dependent manner. These results suggested that C2C12 enables to transdifferentiate into smooth muscle when gene expression patterns are changed by the inhibition of DNA methylation induced by EGCG. In conclusion, transdifferentiation of C2C12 myoblasts into smooth muscle is resulted from the modulating effects of EGCG on DNA methylation which subsequently results in changing the expression pattern of several genes playing a critical role in the differentiation of C2C12 myoblasts.
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      In the present investigation, we studied the modulating effects of (-)-epigallocatechin-3-gallate(EGCG) on the differentiation of mouse C2C12 myoblasts. We found that the strong inhibitory effect of EGCG on DNA methyltransferase-mediated DNA methylati...

      In the present investigation, we studied the modulating effects of (-)-epigallocatechin-3-gallate(EGCG) on the differentiation of mouse C2C12 myoblasts. We found that the strong inhibitory effect of EGCG on DNA methyltransferase-mediated DNA methylation induced transdifferentiation of C2C12 myoblasts into smooth muscle cells demonstrated by both morphological changes and immunofluorescent staining. C2C12 myoblasts treated with EGCG for 4 days expressed smooth muscle ${\alpha}-actin$ protein. Real-time PCR data revealed that smooth muscle ${\alpha}-actin$ mRNA was induced by EGCG treated C2C12 myoblasts in a concentration-dependent manner. Smooth muscle ${\alpha}-actin$ mRNA concentration increased 330% and 490% after 2 and 3 days of 50 ${\mu}M$ of EGCG treatment. The expression of another smooth muscle marker, transgelin, mRNA was also increased up to 9-fold by 4 days of EGCG treatment compared with control in a concentration-dependent manner. These results suggested that C2C12 enables to transdifferentiate into smooth muscle when gene expression patterns are changed by the inhibition of DNA methylation induced by EGCG. In conclusion, transdifferentiation of C2C12 myoblasts into smooth muscle is resulted from the modulating effects of EGCG on DNA methylation which subsequently results in changing the expression pattern of several genes playing a critical role in the differentiation of C2C12 myoblasts.

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      참고문헌 (Reference)

      1 Schmittwolf, C., "in vivo haematopoietic activity is induced in neurosphere cells by chromatin-modifying agents" 24 : 554-556, 2005

      2 Langen R. C., "Tumor necrosis factor-alpha inhibits myogenesis through redox dependent and -independent pathways" 283 : C714-C721, 2002

      3 Springer, M. L., "Transient production of alpha-smooth muscle actin by skeletal myoblasts during differentiation in culture and following intramuscular implantation" 51 : 177-186, 2002

      4 Spin, J. M., "Transcriptional profiling of in vitro smooth muscle cell differentiation identifies specific patterns of gene and pathway activation" 19 : 292-302, 2004

      5 Jones, P. A., "The fundamental role of epigenetic events in cancer" 3 : 415-428, 2002

      6 Fang, M. Z., "Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransfererase and reactivates methylation-silenced gene in cancer cell lines" 63 : 7563-7570, 2003

      7 Park, I. H., "Skeletal myocyte hypertrophy requires mTOR kinase and S6K1" 309 : 211-219, 2005

      8 Li, E., "Role for DNA methylation in genomic imprinting" 336 : 362-365, 1993

      9 Manabe, I., "Recruitment of serum response factor and hyperacetylation of histones at smooth muscle-specific regulatory regions during differentiation of a novel P19-derived in vitro smooth muscle differentiation system" 88 : 1127-1134, 2001

      10 Lee, W. J., "Mechanisms for the inhibition of DNA methyltransferases by tea catechins and bioflavonoids" 68 : 1018-1030, 2005

      1 Schmittwolf, C., "in vivo haematopoietic activity is induced in neurosphere cells by chromatin-modifying agents" 24 : 554-556, 2005

      2 Langen R. C., "Tumor necrosis factor-alpha inhibits myogenesis through redox dependent and -independent pathways" 283 : C714-C721, 2002

      3 Springer, M. L., "Transient production of alpha-smooth muscle actin by skeletal myoblasts during differentiation in culture and following intramuscular implantation" 51 : 177-186, 2002

      4 Spin, J. M., "Transcriptional profiling of in vitro smooth muscle cell differentiation identifies specific patterns of gene and pathway activation" 19 : 292-302, 2004

      5 Jones, P. A., "The fundamental role of epigenetic events in cancer" 3 : 415-428, 2002

      6 Fang, M. Z., "Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransfererase and reactivates methylation-silenced gene in cancer cell lines" 63 : 7563-7570, 2003

      7 Park, I. H., "Skeletal myocyte hypertrophy requires mTOR kinase and S6K1" 309 : 211-219, 2005

      8 Li, E., "Role for DNA methylation in genomic imprinting" 336 : 362-365, 1993

      9 Manabe, I., "Recruitment of serum response factor and hyperacetylation of histones at smooth muscle-specific regulatory regions during differentiation of a novel P19-derived in vitro smooth muscle differentiation system" 88 : 1127-1134, 2001

      10 Lee, W. J., "Mechanisms for the inhibition of DNA methyltransferases by tea catechins and bioflavonoids" 68 : 1018-1030, 2005

      11 Beard, C., "Loss of methylaiton activates Xist in somatic but not embryonic cells" 9 : 2325-2334, 1995

      12 Spangenburg, E. E., "Insulin-like growth factor-induced transcriptional activity of the skeletal alpha-actin gene is regulated by signaling mechani는 linked to voltage-gated calcium channels during myoblast differentiation" 145 : 2054-2063, 2004

      13 Fanzani, A., "Insulin-like growth factor 1 signaling regulates cytosolic sialidase Neu 2 expression during myoblast differentiation and hypertrophy" 273 : 3709-3721, 2006

      14 Lee, W. J., "Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols" 27 : 269-277, 2006

      15 Cheng, J. C., "Inhibition of DNA methylation and reactivation of silenced genes by zebularine" 95 : 399-409, 2003

      16 Herman, J. G., "Hypermethylation of tumor suppressor genes in cancer" 9 : 359-367, 1999

      17 Herman J. G., "Gene silencing in cancer in association with promoter hypermethylation" 349 : 2042-2054, 2004

      18 Wu, H., "Epigenetic regulation of stem cell differentiation" 59 : 21R-25R, 2006

      19 Kondo, T., "Epigenetic alchemy for cell fate conversion" 16 : 502-507, 2006

      20 Esteller, M., "CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future" 21 : 5427-5440, 2002

      21 Jones, P. A., "Cancer epigenetics comes of age" 21 : 163-167, 1999

      22 Momparler, R. L., "Cancer epigenetics" 22 : 6479-6483, 2003

      23 Woodbury, D., "Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis" 69 : 908-917, 2002

      24 Paz, M. F., "A systemic profile of DNA methylation in human cancer cell lines" 63 : 1114-1121, 2003

      25 Schmelz, K., "5-Aza-2'-deoxycytidine induces p21WAF expression by demethylation of p73 leading to p53-independent apoptosis in myeloid leukemia" 114 : 683-695, 2005

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