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Asymmetric dimethylarginine-induced oxidative damage leads to cerebrovascular dysfunction

Neural Regeneration Research 2021年第9期16卷 1793-1794页

作者： Mushfiquddin Khan Inderjit Singh jeseong won Children’s Research Institute Medical University of South CarolinaCharlestonSCUSA

Asymmetric dimethylarginine(ADMA) and its enantiomer, symmetric dimethylarginine(SDMA), are naturally-occurring methylated metabolites of the L-arginine amino acid moiety of proteins followed by proteolysis(Grosse et ... 详细信息

关键词： oxidative moiety symmetric

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Neuroprotective effects of Alda-1 mitigate spinal cord injury in mice:involvement of Alda-1-induced ALDH2 activation-mediated suppression of reactive aldehyde mechanisms

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Neural Regeneration Research 2022年第1期17卷 185-193页

作者： Mushfiquddin Khan Fei Qiao Pavan Kumar S.M.Touhidul Islam Avtar K.Singh jeseong won Inderjit Singh Department of Pediatrics Medical University of South CarolinaCharlestonSCUSA Department of Pathology and Laboratory Medicine Medical University of South CarolinaCharlestonSCUSA Ralph H.Johnson VA Medical Center CharlestonSCUSA

Spinal cord injury(SCI)is associated with high production and excessive accumulation of pathological 4-hydroxy-trans-2-nonenal(4-HNE),a reactive aldehyde,formed by SCI-induced metabolic dysregulation of membrane *** aldehyde load causes redox alteration,neuroinflammation,neurodegeneration,pain-like behaviors,and locomotion *** scavenging of reactive aldehydes results in limited improved motor and sensory *** this study,we targeted the activity of mitochondrial enzyme aldehyde dehydrogenase 2(ALDH2)to detoxify 4-HNE for accelerated functional recovery and improved pain-like behavior in a male mouse model of contusion SCI.N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide(Alda-1),a selective activator of ALDH2,was used as a therapeutic tool to suppress the 4-HNE *** was induced by an impactor at the T9–10 vertebral *** animals were initially treated with Alda-1 at 2 hours after injury,followed by once-daily treatment with Alda-1 for 30 consecutive *** function was evaluated by the Basso Mouse Scale,and pain-like behaviors were assessed by mechanical allodynia and thermal ***2 activity was measured by enzymatic assay.4-HNE protein adducts and enzyme/protein expression levels were determined by western blot analysis and histology/*** resulted in a sustained and prolonged overload of 4-HNE,which parallels with the decreased activity of ALDH2 and low functional ***-1 treatment of SCI decreased 4-HNE load and enhanced the activity of ALDH2 in both the acute and the chronic phases of ***,the treatment with Alda-1 reduced neuroinflammation,oxidative stress,and neuronal loss and increased adenosine 5′-triphosphate levels stimulated the neurorepair process and improved locomotor and sensory ***,the results provide evidence that enhancing the ALDH2 activity by Alda-1 treatment of SCI mice suppresses the 4-HNE load that attenuates neuroinfl

关键词： 4-hydroxy-trans-2-nonenal Alda-1 ALDH2 Basso Mouse Scale score functional recovery mitochondrial function neuroinflammation neuroprotection pain spinal cord injury

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