典型文献
L-Cysteine attenuates osteopontin-mediated neuroinflammation following hypoxia-ischemia insult in neonatal mice by inducing S-sulfhydration of Stat3
文献摘要：
We previously show that L-Cysteine administration significantly suppresses hypoxia-ischemia(HI)-induced neuroinflammation in neonatal mice through releasing H2S.In this study we conducted proteomics analysis to explore the potential biomarkers or molecular therapeutic targets associated with anti-inflammatory effect of L-Cysteine in neonatal mice following HI insult.HI brain injury was induced in postnatal day 7(P7)neonatal mice.The pups were administered L-Cysteine(5 mg/kg)at 24,48,and 72 h post-HI.By conducting TMT-based proteomics analysis,we confirmed that osteopontin(OPN)was the most upregulated protein in ipsilateral cortex 72 h following HI insult.Moreover,OPN was expressed in CD11 b+/CD45low cells and infiltrating CD11 b+/CD45high cells after HI exposure.Intracerebroventricular injection of OPN antibody blocked OPN expression,significantly attenuated brain damage,reduced pro-inflammatory cytokine levels and suppressed cerebral recruitment of CD11b+/CD45high immune cells following HI insult.L-Cysteine administration reduced OPN expression in CD11 b+/CD45high immune cells,concomitant with improving the behavior in Y-maze test and suppressing cerebral recruitment of CD11 b+/CD45high immune cells post-HI insult.Moreover,L-Cysteine administration suppressed the Stat3 activation by inducing S-sulfhydration of Stat3.Intracerebroventricular injection of Stat3 siRNA not only decreased OPN expression,but also reversed HI brain damage.Our data demonstrate that L-Cysteine administration effectively attenuates the OPN-mediated neuroinflammation by inducing S-sulfhydration of Stat3,which contributes to its anti-inflammatory effect following HI insult in neonatal mice.Blocking OPN expression may serve as a new target for therapeutic intervention for perinatal HI brain injury.
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中图分类号：
作者姓名：
Ting-ting Li;Dan-qing Xin;Hong-fei Ke;Xi-li Chu;Yi-jing Zhao;Shou-wei Yue;De-xiang Liu;Zhen Wang
作者机构：
Department of Physiology,School of Basic Medical Sciences,Cheeloo College of Medicine,Shandong University,Ji-nan 250012,China;Department of Medical Psychology and Ethics,School of Basic Medical Sciences,Cheeloo College of Medicine,Shandong University,Ji-nan 250012,China;Rehabilitation Center,Qilu Hospital,Cheeloo College of Medicine,Shandong University,Ji-nan 250012,China
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引用格式：
[1]Ting-ting Li;Dan-qing Xin;Hong-fei Ke;Xi-li Chu;Yi-jing Zhao;Shou-wei Yue;De-xiang Liu;Zhen Wang-.L-Cysteine attenuates osteopontin-mediated neuroinflammation following hypoxia-ischemia insult in neonatal mice by inducing S-sulfhydration of Stat3)[J].中国药理学报（英文版）,2022(07):1658-1669
A类：
sulfhydration,pups,CD45low,CD45high,Intracerebroventricular
B类：
Cysteine,attenuates,osteopontin,mediated,neuroinflammation,following,hypoxia,ischemia,insult,neonatal,mice,by,inducing,Stat3,We,previously,show,that,administration,significantly,suppresses,HI,induced,through,releasing,H2S,this,study,conducted,proteomics,analysis,explore,potential,biomarkers,molecular,therapeutic,targets,associated,inflammatory,brain,injury,was,postnatal,day,P7,were,administered,By,conducting,TMT,confirmed,OPN,most,upregulated,protein,ipsilateral,cortex,Moreover,expressed,cells,infiltrating,after,exposure,injection,antibody,blocked,expression,attenuated,damage,reduced,cytokine,levels,suppressed,cerebral,recruitment,CD11b+,immune,concomitant,improving,behavior,maze,test,suppressing,activation,siRNA,not,only,decreased,also,reversed,Our,data,demonstrate,effectively,which,contributes,its,Blocking,may,serve,new,intervention,perinatal
AB值：
0.395646
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