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Qian Sun, Lili Gong, Ruili Qi, Fang-yuan liu, Zhong-wen Luo, QIAN Nie, Xiao-Dong Gong, Yun-Fei Liu, Lan Zhang, Xiangcheng Tang, Yizhi Liu, David W Li; Protein sumoylation decreases in aging retina and premature senescent retinal pigment epithelial cells. Invest. Ophthalmol. Vis. Sci. 2017;58(8):814.
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Advanced age is the largest risk factor for age-related macular degeneration (AMD). Sumoylation is a reversible post-translational modification that conjugates small peptide SUMO (small ubiquitin-like modifier) to a target protein. Dysregulation of sumoylation is recently found to be critically involved in several age-related disorders, such as Alzheimer’s disease and Parkinson's disease. How sumoylation pathway is regulated during retina aging remains elusive. This study is aimed to investigate sumoylation pathway in the aging retina and premature senescent retinal pigment epithelial (RPE) cells.
In vivo sumoylation regulation was assessed in retina obtained from C57BL/6 mice of 1.5-month to 10-month old. The premature senescence RPE model was established by exposure of ARPE-19 cells to 3.6 mM tert-butylhydroperoxide for 1 h daily for 3 days. The cellular senescence was confirmed by senescence-associated β-galactosidase activity, growth arrest, and cell cycle arrest in G1. Global SUMO1 and SUMO2/3 modifications, the major sumoylation substrate RanGAP1 and the protein levels of sumoylation enzymes E1, E2 and E2 were analyzed by western blot. The localizations of RanGAP1, SUMO1 and SUMO2/3 were further observed by confocal microscopy.
A significantly decreased E1 UBA2, E2 UBC9, E3 PIAS1 and global SUMO1 modification were detected in both physiological aging retina and in premature senescent RPE cells. In senescent RPE cells, indirect immunofluorescence of RanGAP1 showed lobulation of the nuclear envelope, a hallmark of nuclear structure defects. Furthermore, decreased SUMO1 and SUMO2/3 fluorescent signals were found in senescent RPE nuclei.
Together, our data suggest sumoylation may critically regulate retina aging and AMD.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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