ALDH2 protects against stroke by clearing 4-HNE
Jin-Min Guo;Ai-Jun Liu;Pu Zang;Wen-Zhe Dong;Li Ying;Wei Wang;Pu Xu
【期刊名称】《细胞研究（英文版）》 【年(卷),期】2013(023)007
【摘要】Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that metabolizes ethanol and toxic aldehydes such as 4-hydroxy-2-nonenal (4-HNE).Using an unbiased proteomic search,we identified ALDH2 deficiency in stroke-prone spontaneously hypertensive rats (SHR-SP) as compared with spontaneously hypertensive rats (SHR).We concluded the causative role of ALDH2 deficiency in neuronal injury as overexpression or activation of ALDH2conferred neuroprotection by clearing 4-HNE in in vitro studies.Further,ALDH2-knockdown rats revealed the absence of neuroprotective effects of PKCε.Moderate ethanol administration that is known to exert protection against stroke was shown to enhance the detoxification of 4-HNE,and to protect against ischemic cerebral injury through the PKCε-ALDH2 pathway.In SHR-SP,serum 4-HNE level was persistently elevated and correlated inversely with the lifespan.The role of 4-HNE in stroke in humans was also suggested by persistent elevation of its plasma levels for at least 6 months after stroke.Lastly,we observed that 21 of 1 242 subjects followed for 8 years who developed stroke had higher initial plasma 4-HNE levels than those who did not develop stroke.These findings
ALDH2 protects against stroke by clearing 4-HNE
