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Suh, Pann-Ghill
BioSignal Network Lab (BSN)
Research Interests
  • Signal transduction, cancer, metabolism, phospholipase C

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The Glutamate Agonist Homocysteine Sulfinic Acid Stimulates Glucose Uptake through the Calcium-dependent AMPK-p38 MAPK-Protein Kinase C zeta Pathway in Skeletal Muscle Cells

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Title
The Glutamate Agonist Homocysteine Sulfinic Acid Stimulates Glucose Uptake through the Calcium-dependent AMPK-p38 MAPK-Protein Kinase C zeta Pathway in Skeletal Muscle Cells
Author
Kim, Ji HaeLee, Jung OkLee, Soo KyungMoon, Ji WookYou, Ga YoungKim, Su JinPark, Sun-HwaPark, Ji ManLim, Se YoungSuh, Pann-GhillUhm, Kyung-OkSong, Min SeokKim, Hyeon Soo
Keywords
Amino acid cysteine; AMP-activated protein kinase; Cell surfaces; Glucose metabolism; Glucose uptake; Homocysteines; Intracellular calcium; Intracellular calcium concentration; Metabolic roles; Metabotropic glutamate receptors; Myoblast cells; Nitroquinoxaline; P38 MAPK; P38 mitogen-activated protein kinase; Pre-Treatment; Protein kinase; Protein Kinase C; Skeletal muscle cells; Stimulatory effects; Sulfinic acid; Transfected cells; Western-blot analysis
Issue Date
201103
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v.286, no.9, pp.7567 - 7576
Abstract
Homocysteine sulfinic acid (HCSA) is a homologue of the amino acid cysteine and a selective metabotropic glutamate receptor (mGluR) agonist. However, the metabolic role of HCSA is poorly understood. In this study, we showed that HCSA and glutamate stimulated glucose uptake in C2C12 mouse myoblast cells and increased AMP-activated protein kinase (AMPK) phosphorylation. RT-PCR and Western blot analysis revealed that C2C12 expresses mGluR5. HCSA transiently increased the intracellular calcium concentration. Although alpha-methyl-4-carboxyphenylglycine, a metabotropic glutamate receptor antagonist, blocked the action of HCSA in intracellular calcium response and AMPK phosphorylation, 6-cyano-7-nitroquinoxaline-2,3-dione, an AMPA antagonist, did not exhibit such effects. Knockdown of mGluR5 with siRNA blocked HCSA-induced AMPK phosphorylation. Pretreatment of cells with STO-609, a calmodulin-dependent protein kinase kinase (CaMKK) inhibitor, blocked HCSA-induced AMPK phosphorylation, and knockdown of CaMKK blocked HCSA-induced AMPK phosphorylation. In addition, HCSA activated p38 mitogen-activated protein kinase (MAPK). Expression of dominant-negative AMPK suppressed HCSA-mediated phosphorylation of p38 MAPK, and inhibition of AMPK and p38 MAPK blocked HCSA-induced glucose uptake. Phosphorylation of protein kinase C zeta (PKC zeta) was also increased by HCSA. Pharmacologic inhibition or knockdown of p38 MAPK blocked HCSA-induced PKC zeta phosphorylation, and knockdown of PKC zeta suppressed the HCSA-induced increase of cell surface GLUT4. The stimulatory effect of HCSA on cell surface GLUT4 was impaired in FITC-conjugated PKC zeta siRNA-transfected cells. Together, the above results suggest that HCSA may have a beneficial role in glucose metabolism in skeletal muscle cells via stimulation of AMPK.
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DOI
http://dx.doi.org/10.1074/jbc.M110.149328
ISSN
0021-9258
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