title: Ryanodine Receptor 2 Plays a Critical Role in Spinal Cord Injury via Induction of Oxidative Stress.
abstract: OBJECTIVE
  Spinal cord injury (SCI) is a severe health problem worldwide. Ryanodine receptors (RyRs) are a class of intracellular calcium channels in various excitable tissues such as muscles and nervous tissues. The current study was designed to investigate the possible role of RyR2 upregulation in SCI and to elucidate the possible molecular mechanisms.
  
  
  METHODS
  Rats were injected with LVshRNAi- RyR2 and then exposed to spinal cord contusion injury.
  
  
  RESULTS
  The results showed that knockdown of RyR2 significantly promoted the recovery of structural and functional injury in spinal cord, as evidenced by reduction of lesion volume and increase of Basso, Beattie and Bresnahan (BBB) and combined behavioral score (CBS) scores. Knockdown of RyR2 inhibited the increase of proinflammatory cytokines, including IL-1β and TNFα. Moreover, downregulation of RyR2 increased oxygen consumption rate and decreased the expression of glucose-regulated protein 78 (GRP78), activating transcription factor 3 (ATF3) and ATF6, indicating the improvement of mitochondrial dysfunction and endoplasmic reticulum stress after SCI. Furthermore, silence of RyR2 reduced oxidative stress, as reflected by decrease of TBARS and GSSG content and increase of GSH level. The expression of NADPH oxidase 2 (NOX2), NOX4 and p66(shc) were increased in SCI rats. Knockdown of RyR2 significantly decreased NOX2 expression, but had no evident effect on NOX4 and p66shc expression. These results indicated NOX2 may be involved in RyR2-induced ROS generation which mediated contusion-induced spinal cord injury.
  
  
  CONCLUSIONS
  The data provide novel insights into the mechanism of RyR2-mediated injury and the potential therapeutic targets for injury in spinal cord.
authors.forename: Bo
authors.initials: B
authors.lastname: Liao
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Honghui
authors.initials: H
authors.lastname: Sun
authors.forename: Baoan
authors.initials: B
authors.lastname: Ma
authors.forename: Jixian
authors.initials: J
authors.lastname: Qian
mesh_terms: D000818:Animals; D059865:Endoplasmic Reticulum Stress; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics* / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; C000612605:RyR2 protein, rat; D019837:Ryanodine Receptor Calcium Release Channel; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases