NDLI: BMP4 mediates oxidative stress-induced retinal pigment epithelial cell senescence and is overexpressed in age-related macular degeneration.

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BMP4 mediates oxidative stress-induced retinal pigment epithelial cell senescence and is overexpressed in age-related macular degeneration.

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BMP4 mediates oxidative stress-induced retinal pigment epithelial cell senescence and is overexpressed in age-related macular degeneration.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ryan, Stephen J. Spee, Christine Wu, Jian Zhu, Danhong Hinton, David R.
Description	Author Affiliation: Zhu D ( Arnold and Mabel Beckman Macular Research Center, Keck School of Medicine of the University of Southern California, Los Angeles, California 90033, USA.)
Abstract	The retinal pigment epithelium is a primary site of pathology in age-related macular degeneration. Oxidative stress and senescence are both thought to be important mediators of macular degeneration pathogenesis. We demonstrate here that bone morphogenetic protein-4 is highly expressed in the retinal pigment epithelium and adjacent extracellular matrix of patients with dry age-related macular degeneration. In vitro studies revealed that sublethal oxidative stress increased bone morphogenetic protein-4 expression in retinal pigment epithelial cells, and both bone morphogenetic protein-4 and persistent mild oxidative stress can induce retinal pigment epithelial cell senescence through p53-p21(Cip1/WAF1)-Rb pathway. We further demonstrate that bone morphogenetic protein-4 acts as a mediator in oxidative stress-induced senescence and that this mediator function is via Smad and the p38 signaling pathway to increase and activate p53 and p21(Cip1/WAF1) and decrease phospho-Rb. Oxidative stress-induced senescence can be blocked by Chordin-like, an antagonist of bone morphogenetic protein-4, or SB203580, a phospho-p38 inhibitor. Our results suggest that oxidative stress and bone morphogenetic protein-4 may interact to promote retinal pigment epithelial cell senescence and that bone morphogenetic protein-4 may represent a novel therapeutic target to inhibit the progressive effects of oxidative stress and senescence in dry age-related macular degeneration.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	14
Volume Number	284
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2009-04-03
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Bone Morphogenetic Protein 4 Metabolism Cell Aging Physiology Macular Degeneration Oxidative Stress Retinal Pigment Epithelium Genetics Cell Cycle Cells, Cultured Gene Expression Regulation Phosphorylation Smad Proteins P38 Mitogen-Activated Protein Kinases Research Support, N.I.H., Extramural Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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