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Acetaldehyde enhances murine alpha2(I) collagen promoter activity by Ca2+-independent protein kinase C activation in cultured rat hepatic stellate cells.
Alcohol Clin Exp Res. 1999 Feb; 23(2):279-84.AC

Abstract

Protein kinase C (PKC) inhibitors decrease alpha1(I) collagen mRNA in stellate cells exposed to 200 micromol/liter of acetaldehyde. The purpose of these studies was to determine whether PKC activation plays a role in transcriptional activation of the alpha2(I) collagen gene. Cultured stellate cells were exposed to 200 micromol/liter of acetaldehyde. PKC, inositol triphosphate, diacylglycerol (DAG), and intracellular free calcium (Ca2+i) were measured. Alpha1(I) and alpha2(I) collagen messages were determined by reverse transcriptase-polymerase chain reaction. Activation of the alpha2(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 alpha1(I) and alpha2(I) collagen messages in stellate cells. Calphostin C, a specific PKC inhibitor, which blocks DAG binding, eliminated both activation of the alpha2(I) collagen promoter by acetaldehyde and mRNA production by reverse transcriptase-polymerase chain reaction analysis. Similarly, D609, an inhibitor of DAG production, also inhibited alpha2(I) collagen gene expression. This study shows that collagen production by acetaldehyde is mediated by a calcium-independent PKC mechanism.

Authors+Show Affiliations

Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2195, USA. fanania@welchlink.welch.jhu.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10069557

Citation

Anania, F A., et al. "Acetaldehyde Enhances Murine alpha2(I) Collagen Promoter Activity By Ca2+-independent Protein Kinase C Activation in Cultured Rat Hepatic Stellate Cells." Alcoholism, Clinical and Experimental Research, vol. 23, no. 2, 1999, pp. 279-84.
Anania FA, Womack L, Potter JJ, et al. Acetaldehyde enhances murine alpha2(I) collagen promoter activity by Ca2+-independent protein kinase C activation in cultured rat hepatic stellate cells. Alcohol Clin Exp Res. 1999;23(2):279-84.
Anania, F. A., Womack, L., Potter, J. J., & Mezey, E. (1999). Acetaldehyde enhances murine alpha2(I) collagen promoter activity by Ca2+-independent protein kinase C activation in cultured rat hepatic stellate cells. Alcoholism, Clinical and Experimental Research, 23(2), 279-84.
Anania FA, et al. Acetaldehyde Enhances Murine alpha2(I) Collagen Promoter Activity By Ca2+-independent Protein Kinase C Activation in Cultured Rat Hepatic Stellate Cells. Alcohol Clin Exp Res. 1999;23(2):279-84. PubMed PMID: 10069557.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acetaldehyde enhances murine alpha2(I) collagen promoter activity by Ca2+-independent protein kinase C activation in cultured rat hepatic stellate cells. AU - Anania,F A, AU - Womack,L, AU - Potter,J J, AU - Mezey,E, PY - 1999/3/9/pubmed PY - 1999/3/9/medline PY - 1999/3/9/entrez SP - 279 EP - 84 JF - Alcoholism, clinical and experimental research JO - Alcohol Clin Exp Res VL - 23 IS - 2 N2 - Protein kinase C (PKC) inhibitors decrease alpha1(I) collagen mRNA in stellate cells exposed to 200 micromol/liter of acetaldehyde. The purpose of these studies was to determine whether PKC activation plays a role in transcriptional activation of the alpha2(I) collagen gene. Cultured stellate cells were exposed to 200 micromol/liter of acetaldehyde. PKC, inositol triphosphate, diacylglycerol (DAG), and intracellular free calcium (Ca2+i) were measured. Alpha1(I) and alpha2(I) collagen messages were determined by reverse transcriptase-polymerase chain reaction. Activation of the alpha2(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 alpha1(I) and alpha2(I) collagen messages in stellate cells. Calphostin C, a specific PKC inhibitor, which blocks DAG binding, eliminated both activation of the alpha2(I) collagen promoter by acetaldehyde and mRNA production by reverse transcriptase-polymerase chain reaction analysis. Similarly, D609, an inhibitor of DAG production, also inhibited alpha2(I) collagen gene expression. This study shows that collagen production by acetaldehyde is mediated by a calcium-independent PKC mechanism. SN - 0145-6008 UR - https://www.unboundmedicine.com/medline/citation/10069557/Acetaldehyde_enhances_murine_alpha2_I__collagen_promoter_activity_by_Ca2+_independent_protein_kinase_C_activation_in_cultured_rat_hepatic_stellate_cells_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0145-6008&date=1999&volume=23&issue=2&spage=279 DB - PRIME DP - Unbound Medicine ER -