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

Ruiqi Cai, Weili Xue, Shanshan Liu, Robert B. Petersen, Kun Huang, Ling Zheng

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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/Rinduced 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 injuryinduced 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 injuryrelated diseases.

Original languageEnglish
Pages (from-to)2749-2758
Number of pages10
JournalFASEB Journal
Volume29
Issue number7
DOIs
StatePublished - Jul 1 2015

Keywords

  • DNA damage
  • Energy failure
  • I/R injury
  • Necroptosis

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