Hypoglycemia-induced VEGF expression is mediated by intracellular Ca2+ and protein kinase C signaling pathway in HepG2 human hepatoblastoma cells.

S. H. Park, K. W. Kim, Y. S. Lee, J. H. Baek, M. S. Kim, Y. M. Lee, M. S. Lee, Y. J. Kim

Research output: Contribution to journalArticle

Abstract

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that plays a central role in angiogenesis. In this study, we investigated the mechanism of VEGF expression in HepG2 human hepatoblastoma cells under hypoglycemia. The shortage of glucose significantly enhanced VEGF mRNA expression in a time-dependent manner as well as increased DNA-binding activity of AP-1 that plays an important role in VEGF transcription. In addition, treatment of a potent PKC inhibitor, H-7 in glucose-deprived HepG2 cells suppressed hypoglycemia-elevated VEGF expression as well as the increased AP-1 DNA-binding activity. Moreover, we observed that Ca2+ levels remarkably increased under low glucose condition. Consistently, an intracellular Ca2+ chelator, BAPTA/AM significantly decreased hypoglycemia-induced VEGF expression and AP-1 DNA-binding activity. Therefore, these results indicate that increase of intracellular Ca2+ level induces the activation of PKC, which induce the activation of AP-1 leading to the increase of VEGF in glucose-deprived environment. Furthermore, it provides one link in regulation of VEGF with hypoglycemia as well as information to understand how hypoglycemia induces VEGF expression and subsequently leads to tumor angiogenesis.

Original languageEnglish (US)
Pages (from-to)91-96
Number of pages6
JournalInternational Journal of Molecular Medicine
Volume7
Issue number1
StatePublished - Jan 2001
Externally publishedYes

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Hepatoblastoma
Hypoglycemia
Protein Kinase C
Vascular Endothelial Growth Factor A
Transcription Factor AP-1
Glucose
DNA
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Angiogenesis Inducing Agents
Hep G2 Cells
Chelating Agents
Messenger RNA

ASJC Scopus subject areas

  • Genetics

Cite this

Hypoglycemia-induced VEGF expression is mediated by intracellular Ca2+ and protein kinase C signaling pathway in HepG2 human hepatoblastoma cells. / Park, S. H.; Kim, K. W.; Lee, Y. S.; Baek, J. H.; Kim, M. S.; Lee, Y. M.; Lee, M. S.; Kim, Y. J.

In: International Journal of Molecular Medicine, Vol. 7, No. 1, 01.2001, p. 91-96.

Research output: Contribution to journalArticle

Park, S. H. ; Kim, K. W. ; Lee, Y. S. ; Baek, J. H. ; Kim, M. S. ; Lee, Y. M. ; Lee, M. S. ; Kim, Y. J. / Hypoglycemia-induced VEGF expression is mediated by intracellular Ca2+ and protein kinase C signaling pathway in HepG2 human hepatoblastoma cells. In: International Journal of Molecular Medicine. 2001 ; Vol. 7, No. 1. pp. 91-96.
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