Jinyang Ren, Jingchen Gao, Xujin Yao, Xiyuran Wang, Xiangyi Kong, Tao Lin, Hui Wang, Wenlong Ma, Oleg O Glebov, Qi Wan
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引用次数: 0
Abstract
Background: In its tetrameric form, pyruvate kinase M2 isoform (PKM2) catalyzes the last step of glycolysis and plays a key role in the metabolic reprogramming via regulating the signaling of pentose phosphate pathway (PPP). But the role of PKM2 in cerebral ischemia-reperfusion (I/R) injury remains unknown.
Methods: Mice model of middle cerebral artery occlusion (MCAO) and model of oxygen-glucose deprivation (OGD) injury in cultured neurons were established. PKM2 activator or inhibitor were used to test the effects of PKM2 in wild-type and PKM2 (-/-) mice after I/R injury. Biochemical and molecular approach were used to detect the level of PKM2 tetramers and PPP metabolites.
Results: We showed for the first time that ischemia-induced increase of PKM2 activity promoted neuronal death via the suppression of PPP-dependent antioxidant capacity. To identify therapeutic approach that suppresses ischemia-induced increase of PKM2 activity, we tested the effect of bilateral transcranial direct-current stimulation (BtDCS), a newly established BtDCS approach by us, on PKM2 activity after mouse I/R. Our data demonstrated that BtDCS inhibited PKM2 activity in the ischemic neurons. BtDCS also reduced the cerebral infarct volume and the neurological deficits in stroke mice. We found that BtDCS-induced neuroprotection was mediated through the suppression of PKM2 activity after I/R.
Conclusions: Together, this study provided novel evidence that supported PKM2 as a crucial regulator of neuronal metabolism after cerebral I/R injury, and revealed the molecular mechanism by which BtDCS protects against mouse cerebral I/R injury through regulating PKM2-mediated metabolic reprogramming.
期刊介绍：
An international multidisciplinary journal devoted to fundamental research in the brain sciences.
Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed.
With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.
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