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Regulation of the Expression and Activity of Glucose and Lactic Acid Metabolism-Related Genes by Protein Kinase C in Skeletal Muscle Cells
Title: | Regulation of the Expression and Activity of Glucose and Lactic Acid Metabolism-Related Genes by Protein Kinase C in Skeletal Muscle Cells |
Authors: | Otake, Sho Browse this author | Kobayashi, Masaki Browse this author →KAKEN DB | Narumi, Katsuya Browse this author | Sasaki, Shotaro Browse this author | Kikutani, Yurika Browse this author | Furugen, Ayako Browse this author | Watanabe, Meguho Browse this author | Takahashi, Natsuko Browse this author | Ogura, Jiro Browse this author →KAKEN DB | Yamaguchi, Hiroaki Browse this author →KAKEN DB | Iseki, Ken Browse this author →KAKEN DB |
Keywords: | glycolysis | protein kinase C | skeletal muscle |
Issue Date: | Sep-2013 |
Publisher: | Pharmaceutical soc japan |
Journal Title: | Biological & pharmaceutical bulletin |
Volume: | 36 |
Issue: | 9 |
Start Page: | 1435 |
End Page: | 1439 |
Publisher DOI: | 10.1248/bpb.b13-00141 |
PMID: | 23995654 |
Abstract: | Protein kinase C (PKC) modulators are very attractive therapeutic targets in cancer. Since most cancer cells display increased glycolysis, elucidations of the effects of PKC activation on glycolysis is necessary for the development of effective medicine. In the present study, to clarify the role of PKC in the regulation of glycolysis, we examined the effect of phorbol 12-myristate 13-acetate (PMA), a PKC activator, on the expression and activity of glucose and lactic acid metabolism-related genes in human rhabdomyosarcoma cells (RD cells). In parallel to increases in glucose uptake and mRNA levels of glucose transporters (GLUTs) induced by PMA treatment for 6h, the hexokinase (HK) mRNA level and activity were also significantly increased in RD cells. On the other hand, a significant increase in lactate dehydrogenase (LDH) mRNA level and activity was seen when the cells were incubated with PMA for 24h, but not for 6 or 12h, and was associated with lactic acid production. These effects by PMA treatment were markedly suppressed by Bisindolylmaleimide (BIM), a PKC inhibitor. Furthermore, chetomin, a hypoxia-inducible factor 1 (HIF-1) inhibitor, completely abrogated the increment of LDH mRNA level and activity as well as monocarboxylate transporter (MCT) 4, a lactic acid efflux transporter. In conclusion, we found that HK and LDH activity induced by PKC activation was associated with the glucose uptake and lactic acid level and that LDH and MCT4 are modulated by a common factor, HIF-1. |
Type: | article |
URI: | http://hdl.handle.net/2115/54046 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 井関 健
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