Acetaldehyde enhances murine α2(I) collagen promoter activity by Ca2+-independent protein kinase C activation in cultured rat hepatic stellate cells

Frank A. Anania, Lawrence Womack, James J. Potter, Esteban Mezey

Research output: Contribution to journalArticlepeer-review

Abstract

Protein kinase C (PKC) inhibitors decrease α1(I) collagen mRNA in stellate cells exposed to 200 μmol/liter of acetaldehyde. The purpose of these studies was to determine whether PKC activation plays a role in transcriptional activation of the α2(I) collagen gene. Cultured stellate cells were exposed to 200 μmol/liter of acetaldehyde. PKC, inositol triphosphate, diacylglycerol (DAG), and intracellular free calcium (Ca2+(i)) were measured. α1(I) and α2(I) collagen messages were determined by reverse transcriptase-polymerase chain reaction. Activation of the α2(I) collagen promoter was determined in transiently transfected stellate cells. Acetaldehyde exposure enhanced PKC activity translocation to the particulate fraction at 20 min. Acetaldehyde did not increase Ca2+(i), or inositol triphosphate but increased DAG levels at 20 min and 3 hr. Acetaldehyde increased both the α1(I) and α2(I) collagen messages in stellate cells. Calphostin C, a specific PKC inhibitor, which blocks DAG binding, eliminated both activation of the α2(I) collagen promoter by acetaldehyde and mRNA production by reverse transcriptase-polymerase chain reaction analysis. Similarly, D609, an inhibitor of DAG production, also inhibited α2(I) collagen gene expression. This study shows that collagen production by acetaldehyde is mediated by a calcium-independent PKC mechanism.

Original languageEnglish (US)
Pages (from-to)279-284
Number of pages6
JournalAlcoholism: Clinical and Experimental Research
Volume23
Issue number2
DOIs
StatePublished - Feb 1999

Keywords

  • Acetaldehyde
  • Collagen
  • Fibrosis
  • Liver
  • PKC

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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