title: Overexpression of glyceraldehyde 3-phosphate dehydrogenase prevents neurovascular degeneration after retinal injury.
abstract: Ischemia and reperfusion (I/R) injury is a common cause of many vascular and neuronal diseases. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) has been found down-regulated or dysfunctional in several tissues upon I/R injury. To investigate the role of GAPDH in retinal I/R injury-induced neurovascular degeneration, the injured retinas of GAPDH transgenic (Tg) mice and wild-type (WT) littermates were analyzed. I/R injury induced neurovascular degeneration, energy failure, DNA damage, and necroptosis in the retinas of WT mice. In contrast, the GAPDH Tg mice showed resistance to all of these injury-induced abnormalities. In addition, I/R-induced effects were further examined in a neuroblastoma cell line and an endothelial cell line, which were transfected with a vector encoding human GAPDH or a control vector. After I/R challenge, energy failure, DNA damage, and elevation of receptor-interacting serine/threonine-protein kinase (RIP) 1/3 were observed in the cells transfected with the control vector. However, overexpression of GAPDH in these cells prevented the injury-induced RIP3 up-regulation by restoring energy production and preventing DNA damage. Together, the protective role of GAPDH in retinal neurovascular degeneration after I/R injury provides a better understanding of the underlying mechanism of I/R injury and a potential therapeutic target to attenuate I/R injury-related diseases.
authors: *College of Life Sciences, Wuhan University, Wuhan, Hubei, People's Republic of China; Departments of Pathology, Neuroscience, and Neurology, Case Western Reserve University, Cleveland, Ohio, USA; and Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors: Ruiqi
authors: R
authors: Cai
authors: *College of Life Sciences, Wuhan University, Wuhan, Hubei, People's Republic of China; Departments of Pathology, Neuroscience, and Neurology, Case Western Reserve University, Cleveland, Ohio, USA; and Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors: Weili
authors: W
authors: Xue
authors: *College of Life Sciences, Wuhan University, Wuhan, Hubei, People's Republic of China; Departments of Pathology, Neuroscience, and Neurology, Case Western Reserve University, Cleveland, Ohio, USA; and Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors: Shanshan
authors: S
authors: Liu
authors: *College of Life Sciences, Wuhan University, Wuhan, Hubei, People's Republic of China; Departments of Pathology, Neuroscience, and Neurology, Case Western Reserve University, Cleveland, Ohio, USA; and Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors: Robert B
authors: RB
authors: Petersen
authors: *College of Life Sciences, Wuhan University, Wuhan, Hubei, People's Republic of China; Departments of Pathology, Neuroscience, and Neurology, Case Western Reserve University, Cleveland, Ohio, USA; and Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors: Kun
authors: K
authors: Huang
authors: *College of Life Sciences, Wuhan University, Wuhan, Hubei, People's Republic of China; Departments of Pathology, Neuroscience, and Neurology, Case Western Reserve University, Cleveland, Ohio, USA; and Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China lzheng217@hotmail.com.
authors: Ling
authors: L
authors: Zheng
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D004249:DNA Damage; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009336:Necrosis; D018384:Oxidative Stress; D015427:Reperfusion Injury / Q000201:enzymology / Q000235:genetics; D012160:Retina / Q000201:enzymology / Q000293:injuries* / Q000473:pathology; D012162:Retinal Degeneration / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D012171:Retinal Vessels / Q000201:enzymology / Q000473:pathology; D015854:Up-Regulation
chemical_list: D000255:Adenosine Triphosphate; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases
keywords: DNA damage; I/R injury; energy failure; necroptosis