title: Downregulation of miR-199a may play a role in 3-nitropropionic acid induced ischemic tolerance in rat brain.
abstract: MicroRNAs (miR) are single-stranded short RNA molecules that regulate gene expression by degradation or translational repression of mRNA. It has been reported that the downregulation of miR-199a plays an important role in cardiac ischemic tolerance. We examined the expression of miR-199a after 3-nitropropionic acid (3-NPA) preconditioning in rat brain. 3-NPA (20mg/kg), an irreversible inhibitor of succinate dehydrogenase, was injected intraperitoneally to induce ischemic tolerance in rats. For comparison, the control group received intraperitoneal injections of vehicle (0.9% sodium chloride). Quantitative RT-PCR assay was applied to detect the expression of miR-199a. Luciferase reporter assays and Western blotting were used to verify the target genes of miR-199a. In cortex and striatum, miR-199a was downregulated at two separate time intervals (the 2nd and 4th day), while in the hippocampus, it was downregulated on the 2nd day after 3-NPA preconditioning. The maximum reduction of miR-199a was 66.3% in striatum (4th day), 54.9% in hippocampus (2nd day), and 27.6% in cortex (2nd day). The level of sirt1 protein, a putative target of miR-199a and a known mediator of neuroprotective effect in brain ischemic tolerance, decreased significantly in hippocampal neurons by overexpression of miR-199a, while it increased with knockdown of miR-199a. Taking these results together, we hypothesize miR-199a may have a role in the formation of cerebral ischemic tolerance.
authors.affiliation: Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Wei-Hai
authors.initials: WH
authors.lastname: Xu
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Yao
authors.forename: Hao-Jie
authors.initials: HJ
authors.lastname: Yu
authors.forename: Ji-Wei
authors.initials: JW
authors.lastname: Huang
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Cui
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism*; D003292:Convulsants / Q000494:pharmacology; D015536:Down-Regulation; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000235:genetics*; D055785:Gene Knockdown Techniques; D019194:Ischemic Preconditioning / Q000379:methods; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009574:Nitro Compounds / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000096:biosynthesis
chemical_list: D003292:Convulsants; C552425:MIRN199 microRNA, rat; D035683:MicroRNAs; D009574:Nitro Compounds; D011422:Propionates; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; C015392:3-nitropropionic acid