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Oxidative Medicine and Cellular Longevity
Volume 2014 (2014), Article ID 425705, 11 pages
http://dx.doi.org/10.1155/2014/425705
Research Article

Aging Leads to Elevation of O-GlcNAcylation and Disruption of Mitochondrial Homeostasis in Retina

1Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China
2Center for Translational Medicine, The Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China

Received 1 April 2014; Accepted 9 May 2014; Published 29 May 2014

Academic Editor: Liang-Jun Yan

Copyright © 2014 Lin Zhao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Retina is particularly susceptible to aging as oxidative damage accumulates within retina, leading to age-related retinal dysfunction or even visual loss. However, the underlying mechanisms still remain obscure and effective therapeutic strategy is urgently in need. Here, we quested for the answer particularly focusing on mitochondrial homeostasis and O-GlcNAcylation in rat retina. By comparing expression of electron transfer chain complexes and key factors in mitochondrial biogenesis and dynamics in retinas of aged and young Sprague-Dawley rats, we found that mitochondrial Complex I, II, IV and V were increased in aged retina with decreased mtTFA and Mfn2. Also, we noticed that p38 and JNK of MAPK signaling were substantially more activated in aged retina, suggesting stress induction. In addition, we found that pan-O-GlcNAcylation was remarkably stronger with lower OGA expression in aged retina. To further elucidate the roles of Mfn2 and O-GlcNAcylation, we employed ARPE-19 cells and found that ATP production, oxygen consumption, and mitochondrial membrane potential were reduced and ROS level was increased by Mfn2 knockdown, while treating with PUGNAc or UDP-GlcNAc heightened oxygen consumption and reduced ROS. Our results suggest disrupted mitochondrial homeostasis may increase oxidative stress; yet enhanced O-GlcNAcylation might defend against oxidative stress and promote mitochondrial respiration in aged retina.