NDLI: Adenosine induces loss of actin stress fibers and inhibits contraction in hepatic stellate cells via Rho inhibition.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Sohail, Muhammad A. Hashmi, Ardeshir Z. Hakim, Wyel Watanabe, Azuma Zipprich, Alexander Groszmann, Roberto J. Dranoff, Jonathan A. Torok, Natalie J. Mehal, Wajahat Z.
Description	Country affiliation: United States Author Affiliation: Sohail MA ( Section of Digestive Diseases, Yale University, New Haven, CT 06520-8019, USA.)
Abstract	The Rho/ROCK pathway is activated in differentiated hepatic stellate cells (HSCs) and is necessary for assembly of actin stress fibers, contractility, and chemotaxis. Despite the importance of this pathway in HSC biology, physiological inhibitors of the Rho/ROCK pathway in HSCs are not known. We demonstrate that adenosine induces loss of actin stress fibers in the LX-2 cell line and primary HSCs in a manner indistinguishable from Rho/ROCK inhibition. Loss of actin stress fibers occurs via the A2a receptor at adenosine concentrations above 10 muM, which are present during tissue injury. We further demonstrate that loss of actin stress fibers is due to a cyclic adenosine monophosphate, protein kinase A-mediated pathway that results in Rho inhibition. Furthermore, a constitutively active Rho construct can inhibit the ability of adenosine to induce loss of actin stress fibers. Actin stress fibers are required for HSC contraction, and we demonstrate that adenosine inhibits endothelin-1 and lysophosphatidic acid-mediated HSC contraction. We propose that adenosine is a physiological inhibitor of the Rho pathway in HSCs with functional consequences, including loss of HSC contraction.
File Format	HTM / HTML
ISSN	02709139
e-ISSN	15273350
DOI	10.1002/hep.22589
Journal	Hepatology
Issue Number	1
Volume Number	49
Language	English
Publisher	Wiley
Publisher Date	2009-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Hepatology Adenosine Pharmacology Hepatic Stellate Cells Drug Effects Stress Fibers Metabolism Rho-associated Kinases Antagonists & Inhibitors Adenosine-5'-(n-ethylcarboxamide) Animals Cell Line Cyclic Amp Physiology Cyclic Amp-dependent Protein Kinases Endothelin-1 Lysophospholipids Mice Receptor, Adenosine A2a Signal Transduction Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Hepatology

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Adenosine Induces Loss of Actin Stress Fibers and Inhibits Contraction in Hepatic Stellate Cells via Rho Inhibition

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