Role of Ras in Ethanol Modulation of Angiotensin Ii Activated P42/P44 Map Kinase in Rat Hepatocytes.
From: Department of Medical Pharmacology and Physiology, School of Medicine, University of Missouri-Columbia, Columbia, Missouri 65212, USA.
Life sciences
- Publish Date: Nov 2006
- ISSN: 0024-3205
- Volume: 79
- Issue: 25
- Pages: 2357-63
- Medium: Print
- Language: English
- Citation (JAMA): Park Pil-Hoon, Aroor Annayya R, Shukla Shivendra D, et al. Role of Ras in Ethanol Modulation of Angiotensin Ii Activated P42/P44 Map Kinase in Rat Hepatocytes.. Life Sci. Nov 2006;79:2357-63
Abstract
Angiotensin II plays a role in both liver cell proliferation and liver injury but the effects of ethanol on angiotensin II signaling in liver are not clearly understood. We have investigated the role of Ras in ethanol modulation of p42/p44 mitogen-activated protein kinase (MAPK) stimulated by angiotensin II (Ang II) in primary cultures of rat hepatocytes. Hepatocytes were incubated with ethanol (100 mM) for 24 h, then stimulated with Ang II (100 nM). The level of p42/p44 MAPK phosphorylation was measured by Western blot analysis and Ras activation was assessed by specific binding of Ras-GTP (activated form) to a GST-RBD fusion protein containing Ras-binding domain (RBD) of Raf-1. Ethanol potentiated p42/p44 MAPK activation by Ang II, whereas ethanol alone did not significantly affect phosphorylation of p42/p44 MAPK. Ang II increased Ras activity by about 2 fold. Ethanol exposure increased Ang II stimulated Ras activity by an additional about 2 fold. Ethanol alone elicited a small increase in basal Ras activity. Pretreatment with manumycin A (10 microM), a Ras farnesylation inhibitor, partially blocked both Ang II-activated and ethanol-potentiated MAPK activities. These data provided the first evidence that ethanol potentiation of Ang II stimulated p42/p44 MAPK is mediated, in part, by Ras in hepatocytes.
Mesh Headings (Keywords): Angiotensin II, Animals, Blotting, Western, Central Nervous System Depressants, Enzyme Activation, Ethanol, Genes, ras, Guanosine Diphosphate, Guanosine Triphosphate, Hepatocytes, Male, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Phosphorylation, Proto-Oncogene Proteins c-raf, Rats, Rats, Sprague-Dawley, Recombinant Fusion Proteins, Vasoconstrictor Agents
Check for Full Text / PubMed Unique Identifier (PMID): 16950409
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.