Research Spotlight
Professor Zhenghong Qin published a paper in J. Neurosci.

A TIGAR-regulated metabolic pathway is critical for protection of brain ischemia
Mei Li, Meiling Sun, Lijuan Cao, Jinhua Gu, Jianbin Ge, Jieyu Chen, Rong Han, Yuan-Yuan Qin, Zhi-Peng Zhou, Yuqiang Ding, Zheng-Hong Qin *
J. Neurosci., 2014, 34(22):7458–7471 (IF2014= 6.747)

Abstract: TP53-induced glycolysis and apoptosis regulator (TIGAR) inhibits glycolysis and increases the flow of pentose phosphate pathway (PPP), which generates nicotinamide adenine dinucleotide phosphate (NADPH) and pentose. We hypothesized that TIGAR plays a neuroprotective role in brain ischemia as neurons do not rely on glycolysis but are vulnerable to oxidative stress. We found that TIGAR was highly expressed in brain neurons and was rapidly upregulated in response to ischemia/reperfusion insult in a TP53-independent manner. Overexpression of TIGAR in normal mice with lentivirus reduced ischemic neuronal injury, whereas lentivirus-mediated TIGAR knockdown aggravated it. In cultured primary neurons, increasing TIGAR expression reduced OGD/reoxygenation-induced injury, whereas decreasing its expression worsened the injury. The glucose 6-phosphate dehydrogenase (G6PD) was upregulated in mouse and cellular models of stroke and its upregulation was further enhanced by overexpression of TIGAR. Supplementation of NADPH also reduced ischemia/reperfusion brain injury and alleviated TIGAR knockdown-induced aggravation of ischemic injury. In animal and cellular stroke models, ischemia/reperfusion increased mitochondrial localization of TIGAR. OGD/reoxygenation-induced elevation of ROS, reduction of GSH, and dysfunction of mitochondrial were rescued by overexpression of TIGAR or supplementation of NADPH, while knockdown of TIGAR aggravated these changes. Taken together, our results show that TIGAR protects ischemic brain injury via enhancing PPP flux and preserving mitochondria function, and thus may be a valuable therapeutic target for ischemic brain injury.

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