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  • Overexpression of glyceraldehyde 3-phosphate dehydrogenase prevents neurovascular degeneration after retinal injury.

Overexpression of glyceraldehyde 3-phosphate dehydrogenase prevents neurovascular degeneration after retinal injury.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2015-03-26)
Ruiqi Cai, Weili Xue, Shanshan Liu, Robert B Petersen, Kun Huang, Ling Zheng
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
DAPI, for nucleic acid staining
Sigma-Aldrich
DL-Serine, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥98% (HPLC)
Sigma-Aldrich
DL-Serine, ≥98% (TLC)
Sigma-Aldrich
Fluorescein, for fluorescence, free acid