Upregulation of DSCR1 (RCAN1 or Adapt78) in the peri-infarct cortex after experimental stroke.
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 alpha and interleukin-1beta (IL-1beta) 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-1beta-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 TNFalpha and IL-1beta can induce DSCR1-4 transcription, which may be associated with the alleviation of inflammatory processes.
Cho
Kyung-Ok
KO
Department of Pharmacology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, 137-701 Seoul, South Korea.
Kim
Young Sun
YS
Cho
Young-Jin
YJ
Kim
Seong Yun
SY
D000818:Animals; D002135:Calcium-Binding Proteins; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004660:Encephalitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D053583:Interleukin-1beta / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020521:Stroke / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics* / Q000276:immunology
D002135:Calcium-Binding Proteins; C511512:DSCR1 protein, mouse; D053583:Interleukin-1beta; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha