Critical role of mitochondrial aldehyde dehydrogenase 2 in acrolein sequestering in rat spinal cord injury  

作　　者：Seth A.Herr Liangqin Shi Thomas Gianaris Yucheng Jiao Siyuan Sun Nick Race Scott Shapiro Riyi Shi 

机构地区：[1]Center for Paralysis Research&Department of Basic Medical Sciences,College of Veterinary Medicine,Purdue University,West Lafayette,IN,USA [2]Department of Orthopedics,Ruijin Hospital,School of Medicine,Shanghai Jiaotong University,Institute of Trauma and Orthopedics,Shanghai,China [3]Department of Neurological Surgery,Indiana University School of Medicine,Indianapolis,IN,USA

出　　处：《Neural Regeneration Research》2022年第7期1505-1511,共7页中国神经再生研究（英文版）

基　　金：supported by a grant from National Institute of Neurological Disorders and Stroke R21(No.1R21NS115094-01)。

摘　　要：Lipid peroxidation-derived aldehydes,such as acrolein,the most reactive aldehyde,have emerged as key culprits in sustaining post-spinal cord injury(SCI)secondary pathologies leading to functional loss.Strong evidence suggests that mitochondrial aldehyde dehydrogenase-2(ALDH2),a key oxidoreductase and powerful endogenous anti-aldehyde machinery,is likely important for protecting neurons from aldehydesmediated degeneration.Using a rat model of spinal cord contusion injury and recently discovered ALDH2 activator(Alda-1),we planned to validate the aldehyde-clearing and neuroprotective role of ALDH2.Over an acute 2 day period post injury,we found that ALDH2 expression was significantly lowered post-SCI,but not so in rats given Alda-1.This lower enzymatic expression may be linked to heightened acrolein-ALDH2 adduction,which was revealed in co-immunoprecipitation experiments.We have also found that administration of Alda-1 to SCI rats significantly lowered acrolein in the spinal cord,and reduced cyst pathology.In addition,Alda-1 treatment also resulted in significant improvement of motor function and attenuated post-SCI mechanical hypersensitivity up to 28 days post-SCI.Finally,ALDH2 was found to play a critical role in in vitro protection of PC12 cells from acrolein exposure.It is expected that the outcome of this study will broaden and enhance anti-aldehyde strategies in combating post-SCI neurodegeneration and potentially bring treatment to millions of SCI victims.All animal work was approved by Purdue Animal Care and Use Committee(approval No.1111000095)on January 1,2021.

关 键 词：ACROLEIN acrolein-lysine adduct alda-1 enzymatic catalyst lipid peroxidation mitochondrial aldehyde dehydrogenase-2 NEUROTRAUMA oxidative stress reactive aldehydes spinal cord contusion 

分 类 号：R453[医药卫生—治疗学] R364[医药卫生—临床医学]