Upregulation of DSCR1 (RCAN1 or Adapt78) in the peri-infarct cortex after experimental stroke

Kyung Ok Cho, Young Sun Kim, Young Jin Cho, Seong Yun Kim

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Down syndrome candidate region 1 (DSCR1; also known as RCAN1 or Adapt78) has been shown to be induced by calcium overload and oxidative stress which are included in the pathogenic hallmarks of the ischemic diseases. After ischemic stroke, inflammatory responses play an important role in the exacerbation of neuronal loss. In this study, we investigated the expression pattern of DSCR1 in the mouse cortex after transient middle cerebral artery occlusion (MCAO). Then, in vitro studies were taken to address whether inflammatory mediators could induce DSCR1. Male C57BL/6 mice were subjected to transient MCAO for 35 min and sacrificed at 6, 24, and 72 h after the reperfusion. The expression of DSCR1 began to increase in layer VI of the peri-infarct cortex at 24 h and was prominently enhanced at 72h after transient MCAO. Moreover, real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry showed that the induction of the DSCR1 isoform 4 (DSCR1-4) mRNA preceded the expression of the DSCR1 protein. In in vitro studies, tumor necrosis factor α and interleukin-1β (IL-1β) were found to induce strong upregulation of DSCR1-4 mRNA. Furthermore, western blot analysis revealed that overexpression of DSCR1-4 in SK-N-SH neuroblastoma cells attenuated IL-1β-induced cyclooxygenase 2 and intercellular adhesion molecule 1 expression. These results demonstrate upregulation of DSCR1 in the mouse peri-infarct cortex following transient MCAO. In addition, our results suggest that inflammatory mediators such as TNFα and IL-1β can induce DSCR1-4 transcription, which may be associated with the alleviation of inflammatory processes.

Original languageEnglish (US)
Pages (from-to)85-92
Number of pages8
JournalExperimental Neurology
Volume212
Issue number1
DOIs
StatePublished - Jul 1 2008

Keywords

  • Adapt78
  • DSCR1
  • Inflammation
  • Interleukin-1β
  • RCAN1
  • Stroke
  • Tumor necrosis factor α

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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