title: Nitric oxide leads to cytoskeletal reorganization in the retinal pigment epithelium under oxidative stress.
abstract: Light is a risk factor for various eye diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP). We aim to understand how cytoskeletal proteins in the retinal pigment epithetlium (RPE) respond to oxidative stress, including light and how these responses affect apoptotic signaling. Previously, proteomic analysis revealed that the expression levels of vimentin and serine/threonine protein phosphatase 2A (PP2A) are significantly increased when mice are exposed under continuous light for 7 days compared to a condition of 12 hrs light/dark cycling exposure using retina degeneration 1 (rd1) model. When melatonin is administered to animals while they are exposed to continuous light, the levels of vimentin and PP2A return to a normal level. Vimentin is a substrate of PP2A that directly binds to vimentin and dephosphorylates it. The current study shows that upregulation of PP2Ac (catalytic subunit) phosphorylation negatively correlates with vimentin phosphorylation under stress condition. Stabilization of vimentin appears to be achieved by decreased PP2Ac phosphorylation by nitric oxide induction. We tested our hypothesis that site-specific modifications of PP2Ac may drive cytoskeletal reorganization by vimentin dephosphorylation through nitric oxide signaling. We speculate that nitric oxide determines protein nitration under stress conditions. Our results demonstrate that PP2A and vimentin are modulated by nitric oxide as a key element involved in cytoskeletal signaling. The current study suggests that external stress enhances nitric oxide to regulate PP2Ac and vimentin phosphorylation, thereby stabilizing or destabilizing vimentin. Phosphorylation may result in depolymerization of vimentin, leading to nonfilamentous particle formation. We propose that a stabilized vimentin might act as an anti-apoptotic molecule when cells are under oxidative stress.
authors.affiliation: Department of Biological Sciences, Michigan Technological University, Houghton, USA.
authors.forename: Srinivas R
authors.initials: SR
authors.lastname: Sripathi
authors.affiliation: Department of Biological Sciences, Michigan Technological University, Houghton, USA.|Department of Biomedical Engineering, Michigan Technological University, Houghton, USA.
authors.forename: Weilue
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Biological Sciences, Michigan Technological University, Houghton, USA.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Um
authors.affiliation: Department of Biological Sciences, Michigan Technological University, Houghton, USA.
authors.forename: Trevor
authors.initials: T
authors.lastname: Moser
authors.affiliation: Department of Biological Sciences, Michigan Technological University, Houghton, USA.
authors.forename: Stevie
authors.initials: S
authors.lastname: Dehnbostel
authors.affiliation: Department of Biological Sciences, Michigan Technological University, Houghton, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Kindt
authors.affiliation: Department of Biomedical Engineering, Michigan Technological University, Houghton, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Goldman
authors.affiliation: Department of Biomedical Engineering, Michigan Technological University, Houghton, USA.
authors.forename: Megan C
authors.initials: MC
authors.lastname: Frost
authors.affiliation: Department of Biological Sciences, Michigan Technological University, Houghton, USA.|Retina Proteomics Laboratory, Department of Petroleum Chemistry, American University of Nigeria, Yola, Nigeria.
authors.forename: Wan Jin
authors.initials: WJ
authors.lastname: Jahng
keywords: Nitric Oxide; Oxidative Stress; PP2A; Retinal Pigment Epithelium; Vimentin