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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

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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
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 井関 健

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