title: Involvement of microRNA-135a-5p in the Protective Effects of Hydrogen Sulfide Against Parkinson's Disease.
abstract: OBJECTIVE
  Development of effective therapeutic drugs for Parkinson's disease is in great need. During the progression of Parkinson's disease, Rho-associated protein kinase 2 (ROCK2) is activated to promote neurodegeneration. Hydrogen sulfide (H2S) has a neuroprotective effect during the neural injury of Parkinson's disease. However, the mechanisms that underlie the effects of ROCK2 and H2S remain ill-defined. In the current study, we addressed these questions.
  
  
  METHODS
  We used a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse subacute model of Parkinson's disease to study the effects of H2S on astrocytic activation in the mouse striatum, on the levels of tyrosine-hydroxylase (TH)-positive neuron loss, on the apomorphine-induced rotational behavior of the mice, and on the changes in ROCK2 and miR-135a-5p expression. Plasmid transfection was applied to modify miR-135a-5p levels in a neuronal cell line HCN-1A. Bioinformatics analysis was performed to predict the relationship between ROCK2 and miR-135a-5p in neuronal cells, and then was confirmed by luciferase reporter assay.
  
  
  RESULTS
  H2S alleviated MPTP-induced astrocytic activation in the mouse striatum, alleviated the increases in TH-positive neuron loss, and improved the apomorphine-induced rotational behavior of the mice. H2S significantly attenuated the increases in ROCK2 and the decreases in miR-135a-5p by MPTP. MiR-135a-5p targeted the 3'-UTR of ROCK2 mRNA to inhibit its translation in neuronal cells.
  
  
  CONCLUSIONS
  MiR-135a-5p-regulated ROCK2 may play a role in the protective effects of hydrogen sulfide against Parkinson's disease.
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Shengtao
authors.initials: S
authors.lastname: Liao
authors.forename: Hongyu
authors.initials: H
authors.lastname: Quan
authors.forename: Yuhan
authors.initials: Y
authors.lastname: Lin
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Yang
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D001522:Behavior, Animal / Q000187:drug effects; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012399:Rotation; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C544965:MIRN135 microRNA, human; D035683:MicroRNAs; C549289:Mirn135 microRNA, mouse; D020011:Protective Agents; D012333:RNA, Messenger; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C515855:Rock2 protein, mouse; D054460:rho-Associated Kinases; D001058:Apomorphine; D004298:Dopamine; D006862:Hydrogen Sulfide