Clozapine activates AMP-activated protein kinase (AMPK) in C2C12 myotube cells and stimulates glucose uptake

Ji Hae Kim, Jung Ok Lee, Soo Kyung Lee, Jin Hee Jung, Ga Young You, Sun-Hwa Park, Munho Park, Sang-Dae Kim, Hyeon Soo Kim

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Aims: Clozapine has previously been implicated in the dysregulation of energy balance and glucose metabolism in the central nervous system, but its effects in the periphery have yet to be thoroughly elucidated. The objective of this study was to characterize the effects of clozapine on AMP-activated protein kinase (AMPK) activity in the skeletal muscles. Main methods: Myotube C2C12 cells were incubated under control conditions, or with clozapine. Expression levels of phosphorylation status of AMPK and its direct downstream Acetyl-CoA carboxylase (ACC) were analyzed by Western blot. Intracellular calcium concentration was measured with calcium indicator dye, fluo-3. AM. 2-deoxyglucose uptake was assessed via the scintillation count. Key findings: We reported that clozapine activated AMPK in mouse C2C12 myotubes and also stimulated glucose uptake. Clozapine also increased intracellular calcium concentrations of C2C12 cells, and pretreatment with either ethylenediaminetetraacetic acid (EDTA), an extracellular calcium chelator, or 1.8-naphthoylene benzimidazole-3-carboxylic acid (STO-609), a Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) inhibitor, blocked clozapine-induced AMPK activation. Significance: These results demonstrate that clozapine increases glucose uptake through CaMKK-AMPK pathway in myotube C2C12 cells.

Original languageEnglish
Pages (from-to)42-48
Number of pages7
JournalLife Sciences
Volume87
Issue number1-2
DOIs
Publication statusPublished - 2010 Jul 1

Fingerprint

AMP-Activated Protein Kinases
Clozapine
Skeletal Muscle Fibers
Glucose
Calcium-Calmodulin-Dependent Protein Kinases
Calcium
Acetyl-CoA Carboxylase
Phosphorylation
Deoxyglucose
Neurology
Scintillation
Carboxylic Acids
Energy balance
Metabolism
Edetic Acid
Muscle
Skeletal Muscle
Coloring Agents
Phosphotransferases
Central Nervous System

Keywords

  • AMPK
  • C2C12 myotubes
  • Calcium
  • CaMKK
  • Clozapine

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Clozapine activates AMP-activated protein kinase (AMPK) in C2C12 myotube cells and stimulates glucose uptake. / Kim, Ji Hae; Lee, Jung Ok; Lee, Soo Kyung; Jung, Jin Hee; You, Ga Young; Park, Sun-Hwa; Park, Munho; Kim, Sang-Dae; Kim, Hyeon Soo.

In: Life Sciences, Vol. 87, No. 1-2, 01.07.2010, p. 42-48.

Research output: Contribution to journalArticle

Kim, Ji Hae ; Lee, Jung Ok ; Lee, Soo Kyung ; Jung, Jin Hee ; You, Ga Young ; Park, Sun-Hwa ; Park, Munho ; Kim, Sang-Dae ; Kim, Hyeon Soo. / Clozapine activates AMP-activated protein kinase (AMPK) in C2C12 myotube cells and stimulates glucose uptake. In: Life Sciences. 2010 ; Vol. 87, No. 1-2. pp. 42-48.
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