NDLI: The constitutively active orphan G-protein-coupled receptor GPR39 protects from cell death by increasing secretion of pigment epithelium-derived growth factor.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Sahin, Mert Toutzaris, Diamandis Methner, Axel Dittmer, Sonja Pina, Ana-luisa Pantlen, Anna Geerts, Andreas Saxena, Ambrish Golz, Stefan
Description	Author Affiliation: Dittmer S ( Research Group Protective Signaling, Department of Neurology, Heinrich Heine Universität Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany.)
Abstract	GPR39 is a constitutively active orphan G-protein-coupled receptor capable of increasing serum response element-mediated transcription. We found GPR39 to be up-regulated in a hippocampal cell line resistant against diverse stimulators of cell death and show that its overexpression protects against oxidative and endoplasmic reticulum stress, as well as against direct activation of the caspase cascade by Bax overexpression. In contrast, silencing GPR39 rendered cells more susceptible to cell death. An array analysis of transcripts induced by GPR39 revealed up-regulation of RGS16 (inhibitor of G-protein signaling 16), which suggested coupling to Galpha(13) and induction of serum response element-mediated transcription by the small GTPase RhoA. In line with this, co-expression of GPR39 with RGS16, dominant-negative RhoA, or serum response factor abolished cell protection, whereas overexpression of the serum response factor protected from cell death. Further downstream the signaling cascade, GPR39 overexpression leads to increased secretion of the cytoprotective pigment epithelium-derived growth factor (PEDF). Medium conditioned by cells overexpressing GPR39 contained 4-fold more PEDF, and when stripped off it lost most but not all of its protective properties. We conclude that GPR39 is a novel inhibitor of cell death, which might represent a therapeutic target with implications for processes involving apoptosis and endoplasmic reticulum stress like cancer, ischemia/reperfusion injury, and neurodegenerative disease.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	11
Volume Number	283
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2008-03-14
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Eye Proteins Metabolism Gene Expression Regulation Nerve Growth Factors Receptors, G-Protein-Coupled Serpins Animals Culture Media, Conditioned Pharmacology Endoplasmic Reticulum Gene Silencing Mice Models, Biological RGS Proteins Tunicamycin Bcl-2-Associated X Protein RhoA GTP-Binding Protein Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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