alexa PPAR Agonist Effects on Notch Signaling Mediators in Experimental Chronic Alcohol-Induced Steatohepatitis | OMICS International | Abstract
ISSN: 2168-9652

Biochemistry & Physiology: Open Access
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Research Article

PPAR Agonist Effects on Notch Signaling Mediators in Experimental Chronic Alcohol-Induced Steatohepatitis

Diana L Borgas, Chetram Deochand, Ming Tong, and Suzanne M de la Monte*
Liver Research Center, Divisions of Gastroenterology and Neuropathology, and Departments of Medicine, Pathology, Neurology, and Neurosurgery, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Providence, USA
*Corresponding Author : Suzanne M. de la Monte, MD, MPH
Pierre Galletti Research Building
Rhode Island Hospital, 55 Claverick Street
Room 419, Providence,USA
Tel: 401-444-7364
Fax: 401-444-2939
E-mail: [email protected]
Received October 31, 2014; Accepted November 10, 2014, Published November 17, 2014
Citation: Borgas DL, Deochand C, Tong M, de la Monte SM (2014) PPAR Agonist Effects on Notch Signaling Mediators in Experimental Chronic Alcohol-Induced Steatohepatitis. Biochem Physiol 3:145. doi:10.4172/2168-9652.1000145
Copyright: © 2014 Borgas DL, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Aspartyl-Asparaginyl-Β-Hydroxylase (ASPH) is a downstream target of insulin and IGF signaling and promotes cell motility for liver remodeling and repair. ASPH functions in part by activating Notch and HIF-1α. PPAR agonists can ameliorate steatohepatitis, hepatic insulin resistance, and reduced ASPH expression in experimental alcoholic liver disease. Herein, we examine the effects of PPAR-α, PPAR-δ, and PPAR-γ agonists on Notch and HIF-1α signaling. Methods: Long Evans rats were chronically fed control or ethanol-containing diets and treated with vehicle, or a PPAR-α, PPAR-δ, or PPAR-γ agonist. ASPH, Notch, and HIF-1α-related genes and proteins were measured in liver. Results: ASPH, Notch, and HIF-1α signaling genes and/or proteins were inhibited by chronic ethanol feeding. PPAR-δ and/or PPAR-γ agonists normalized ASPH, HIF-1α, and PCNA protein in ethanol-exposed livers. In contrast, Notch signaling through HES-1 was not restored. Conclusion: Therapeutic effects of PPAR-δ and PPAR-γ agonists in alcoholic liver disease are mediated by post-translational mechanisms that bolster ASPH-HIF-1α signaling. Alternative strategies are needed to circumvent ethanol-mediated uncoupling of cross-talk among insulin/IGF-1/ASPH-Notch networks.

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