Up-regulation of the mitochondrial malate dehydrogenase by oxidative stress is mediated by miR-743a.

摘要: These experiments reveal for the first time that microRNAs mediate oxidant regulated expression of a mitochondrial tricarboxylic acid cycle gene (mdh2). mdh2 encoded malate dehydrogenase (MDH) is elevated by an unknown mechanism in brains patients died with Alzheimer’s disease (AD). Oxidative stress, early and pervasive event AD, increased MDH activity mRNA level 19% 22%, respectively, mouse hippocampal cell line (HT22). Post-transcriptional events underlie change because Actinomycin D did not block mRNA. Since regulate post-transcriptionally, miR-743a, microRNA predicted to target mdh2, was determined showed 52% reduction after treatment. Direct interaction miR-743a demonstrated luciferase based assay. Over-expression or inhibition led respective increase endogenous activity. The results demonstrate negatively regulates at post-transcriptional directly targeting 3′ UTR. findings are consistent suggestion oxidative stress can elevate through provide new insights into possible roles neurodegeneration.