Oxygen-glucose deprivation inducing B1 RNA inhibits neuronal cells metabolic activity by NLRP3 and associated proinflammatory cytokines production

Neurosci Lett. 2015 Feb 19:588:147-53. doi: 10.1016/j.neulet.2014.12.045. Epub 2014 Dec 24.

Abstract

Cerebral ischemia occurs when blood flow to part of the brain is obstructed, which can result in oxygen and glucose deprivation (OGD) and neuronal damage. However, the mechanisms remain poorly understood. The present study investigated the production and effects of double-stranded RNA (dsRNA) induced by OGD in neuronal cells. By confocal microscopy, dsRNA containing B1 and B2 RNA, was found accumulating in HT22 cells under OGD treatment. The sequence of B1 RNA was identified and transfected into HT22 cells. Interestingly, B1 RNA induced transcription and expression of NLRP3, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α, which was similar to the effects of OGD treatment. Moreover, HT22 cell growth inhibition and proinflammatory cytokines production induced by OGD and B1 RNA treatment were down-regulated by NLRP3 knock-down. These findings suggest that B1 RNA induced by OGD forms as dsRNA and inhibits neuronal cell metabolic activity by regulating the NLRP3 and associated proinflammatory cytokines production.

Keywords: B1 RNA; Cerebral ischemia; NLRP3; Oxygen and glucose deprivation; dsRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Glucose / deficiency*
  • Infarction, Middle Cerebral Artery / pathology
  • Interleukin-1beta / biosynthesis
  • Interleukin-1beta / genetics
  • Mice, Inbred BALB C
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Neurons / pathology
  • Oxygen / metabolism*
  • Plasmids
  • RNA / genetics*
  • RNA, Double-Stranded / genetics*
  • Retroelements*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Carrier Proteins
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • RNA, Double-Stranded
  • Retroelements
  • Tumor Necrosis Factor-alpha
  • RNA
  • Glucose
  • Oxygen