title: Valproic Acid Induced Human Retinal Pigment Epithelial Cell Death as Well as its Survival after Hydrogen Peroxide Damage is Mediated by P38 Kinase.
abstract: Age-related macular degeneration (AMD) is a leading cause of legal blindness in developed countries. Several new drugs are now available to reduce the sight threatening complications of this disease, however, all are useful in only a small fraction of patients and none of them prevents disease development. An understanding of the pathogenesis of the retinal and macular degeneration is the first step in developing preventive and fully effective treatment options for this condition. Lifelong oxidative stress seems to be an etiologic factor. In this study, we used cultured human retinal pigment epithelial cells to study the mechanism of cell death and survival in cells exposed to oxidative stress. Our studies demonstrate that valproic acid (VPA), an epigenetic factor, reduces apoptosis in hRPE cells that were subjected to hydrogen peroxide-induced oxidative injury by alteration in P38 kinase activity. Since VPA has been shown to have therapeutic use in other neuronal diseases, better understanding of the mechanism of this VPA anti-apoptotic activity may enhance its development as a therapeutic agent.
authors.affiliation: Department of Ophthalmology, University of Michigan Medical Center, 1000 Wall Street, 48105, Ann Arbor, MI, USA. kotha@umich.edu.
authors.forename: Piyush C
authors.initials: PC
authors.lastname: Kothary
authors.affiliation: Department of Ophthalmology, University of Michigan Medical Center, 1000 Wall Street, 48105, Ann Arbor, MI, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rossi
authors.affiliation: Department of Ophthalmology, University of Michigan Medical Center, 1000 Wall Street, 48105, Ann Arbor, MI, USA.
authors.forename: Monte A
authors.initials: MA
authors.lastname: Del Monte
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology*; D014635:Valproic Acid / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016877:Oxidants; D017382:Reactive Oxygen Species; D014635:Valproic Acid; D006861:Hydrogen Peroxide; D048051:p38 Mitogen-Activated Protein Kinases