Regulation of human monocarboxylate transporter 4 in skeletal muscle cells: The role of protein kinase C (PKC)

Narumi, Katsuya; Kobayashi, Masaki; Otake, Sho; Furugen, Ayako; Takahashi, Nobuo; Ogura, Jiro; Itagaki, Shirou; Hirano, Takeshi; Yamaguchi, Hiroaki; Iseki, Ken

doi:10.1016/j.ijpharm.2012.02.021

Cited by 19 publications

(21 citation statements)

References 42 publications

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“…RD cells are frequently used as an in vitro skeletal muscle model [9][10][11]. The cells were maintained in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 100 units/mL penicillin G, and 100 µg/mL streptomycin.…”

Section: Cell Studiesmentioning

confidence: 99%

Decreased ATP synthesis and lower pH may lead to abnormal muscle contraction and skin sensitivity in human skin

Kim

Lee

Kim

et al. 2014

Journal of Dermatological Science

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Section: Cell Studiesmentioning

confidence: 99%

Decreased ATP synthesis and lower pH may lead to abnormal muscle contraction and skin sensitivity in human skin

Kim

Lee

Kim

et al. 2014

Journal of Dermatological Science

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“…A previous study showed that exposure of RD cells to PMA resulted in a significant increase in MCT4 mRNA level from 12 to 24 h and HIF-1α protein level was increased in a time-dependent manner. 16) It has also been shown that PKC is activated by hypoxia 17) and that PKC increases the protein stability and transcriptional activity of HIF-1α in human cancer cells. 18) We hypothesized that the expression of LDH and that of MCT4 are regulated by a common factor, HIF-1.…”

Section: Regulation Of the Expression And Activity Of Lactic Acid Metmentioning

confidence: 99%

Regulation of the Expression and Activity of Glucose and Lactic Acid Metabolism-Related Genes by Protein Kinase C in Skeletal Muscle Cells

Otake

Kobayashi

Narumi

et al. 2013

Biological & Pharmaceutical Bulletin

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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 6 h, 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 24 h, but not for 6 or 12 h, 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. Key words glycolysis; protein kinase C; skeletal muscleGlucose is widely recognized as a central compound in metabolism, and glucose homeostasis as a whole is highly regulated in physiology.1) Glucose utilization is related to the ability of glucose to transfer across the plasma membrane, a step in which glucose transporters (GLUTs) play an essential role.2) The absorbed glucose is then phosphorylated by hexokinase (HK) in the cytoplasm to form glucose-6-phosphate for metabolic utilization, the first step of glucose metabolism. Two isoforms of HK (type I and type II) are expressed in skeletal muscle.3) On the other hand, lactate dehydrogenase (LDH) mediates lactic acid production from glucose metabolites 4) and human LDH-the M form, predominantly found in muscle; and the H form, found mainly in cardiac muscle.5) The lactic acid produced by LDH was released by monocarboxylate transporter (MCT) 4. MCT4 is thought to play a primary role in the efflux of lactic acid from muscle fibers, and its expression has been shown to be associated with indices of glycolytic capacities, 6) Halestrap and Price reported that MCT4 might be of particular importance in organization that depends on high levels of glycolysis to comply their energy needs. 7)Protein kinase C (PKC) plays important roles in intracellular signaling involved in many cellular responses. 8) PKC activation occurs during contractions of rat skeletal muscle. 9)Moreover, there is evidence that some PKC isoforms have a role in exercise-mediated glucose transport.10) And PKC affected th...

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“…21 On the other hand, MCT4 siRNA 2 prevented these statin-induced reductions of cell viability and caspase-3/7 activation as in the case of atorvastatin. These observations 13 indicate that suppression of MCT4 expression leads to prevention of statin-induced reduction of cell viability and apoptosis.…”

Section: Effects Of Atorvastatin On Cell Viability and Expression Of mentioning

confidence: 70%

“…We previously reported that alteration of monocarboxylate transporter (MCT) 4 function was associated with MCT4 expression levels in RD cells 13 and that lipophilic statins, atorvastatin, simvastatin and fluvastatin, significantly reduced RD cell viability in a concentration-dependent manner. 17 We therefore used RD cells and atorvastatin, simvastatin and fluvastatin in this study.…”

Section: Effects Of Atorvastatin On Cell Viability and Expression Of mentioning

confidence: 99%

“…11 We previously reported that AMPK activation induced expression of MCT4 12 and that MCT4 expression was mediated through PKCδ in an RD cell line as a model of in vitro skeletal muscle. 13 Although we previously reported that α-cyano-4-hydroxycinnamate (CHC), an MCT4 inhibitor, increased the inhibition of growth of RD cells induced by cerivastatin, one of the statins, 14 it is unclear whether statin-induced RD cell cytotoxicity is associated with MCT4 expression. The aim of this study was to determine the relationship between statin-induced cytotoxicity and MCT4 expression in RD cells.…”

Section: Introductionmentioning

confidence: 99%

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Involvement of Monocarboxylate Transporter 4 Expression in Statin-Induced Cytotoxicity

Kikutani

Kobayashi

Konishi

et al. 2016

Journal of Pharmaceutical Sciences

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Regulation of human monocarboxylate transporter 4 in skeletal muscle cells: The role of protein kinase C (PKC)

Cited by 19 publications

References 42 publications

Decreased ATP synthesis and lower pH may lead to abnormal muscle contraction and skin sensitivity in human skin

Decreased ATP synthesis and lower pH may lead to abnormal muscle contraction and skin sensitivity in human skin

Regulation of the Expression and Activity of Glucose and Lactic Acid Metabolism-Related Genes by Protein Kinase C in Skeletal Muscle Cells

Involvement of Monocarboxylate Transporter 4 Expression in Statin-Induced Cytotoxicity

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