PRDX6-iPLA2 aggravates neuroinflammation after ischemic stroke via regulating astrocytes-induced M1 microglia

作者全名："Peng, Li; Ji, Yanyan; Li, Yixin; You, Yan; Zhou, Yang"

作者地址："[Peng, Li; Ji, Yanyan; Zhou, Yang] Chongqing Med Univ, Coll Basic Med, Dept Pathol, Chongqing, Peoples R China; [Peng, Li; Ji, Yanyan; Zhou, Yang] Chongqing Med Univ, Mol Med Diagnost & Testing Ctr, Chongqing, Peoples R China; [Peng, Li; Ji, Yanyan; Zhou, Yang] Chongqing Med Univ, Affiliated Hosp 1, Dept Pathol, Chongqing, Peoples R China; [Li, Yixin] Chongqing Med Univ, Affiliated Hosp 1, Ctr Clin Mol Med Detect, Chongqing 400016, Peoples R China; [You, Yan] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurosurg, Chongqing, Peoples R China"

通信作者："Zhou, Y (通讯作者)，Chongqing Med Univ, Coll Basic Med, Dept Pathol, Chongqing, Peoples R China.; Zhou, Y (通讯作者)，Chongqing Med Univ, Mol Med Diagnost & Testing Ctr, Chongqing, Peoples R China.; Zhou, Y (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Pathol, Chongqing, Peoples R China."

来源：CELL COMMUNICATION AND SIGNALING

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001152191700002

JCR分区：Q2

影响因子：8.4

年份：2024

卷号：22

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：PRDX6-iPLA2; Astrocytes; Microglia; Nox2; Drp1-dependent mitchondrial fission

摘要："The crosstalk between astrocytes and microglia plays a pivotal role in neuroinflammation following ischemic stroke, and phenotypic distribution of these cells can change with the progression of ischemic stroke. Peroxiredoxin (PRDX) 6 phospholipase A2 (iPLA2) activity is involved in the generation of reactive oxygen species(ROS), with ROS driving the activation of microglia and astrocytes; however, its exact function remains unexplored. MJ33, PRDX6D140A mutation was used to block PRDX6-iPLA2 activity in vitro and vivo after ischemic stroke. PRDX6T177A mutation was used to block the phosphorylation of PRDX6 in CTX-TNA2 cell lines. NAC, GSK2795039, Mdivi-1, U0126, and SB202190 were used to block the activity of ROS, NOX2, mitochondrial fission, ERK, and P38, respectively, in CTX-TNA2 cells. In ischemic stroke, PRDX6 is mainly expressed in astrocytes and PRDX6-iPLA2 is involved in the activation of astrocytes and microglia. In co-culture system, Asp140 mutation in PRDX6 of CTX-TNA2 inhibited the polarization of microglia, reduced the production of ROS, suppressed NOX2 activation, and inhibited the Drp1-dependent mitochondrial fission following OGD/R. These effects were further strengthened by the inhibition of ROS production. In subsequent experiments, U0126 and SB202190 inhibited the phosphorylation of PRDX6 at Thr177 and reduced PRDX6-iPLA2 activity. These results suggest that PRDX6-iPLA2 plays an important role in the astrocyte-induced generation of ROS and activation of microglia, which are regulated by the activation of Nox2 and Drp1-dependent mitochondrial fission pathways. Additionally, PRDX6-iPLA2 activity is regulated by MAPKs via the phosphorylation of PRDX6 at Thr177 in astrocytes."

基金机构："National Natural Science Youth Foundation of China [81801183, 82101376]"

基金资助正文：The study was funded by the National Natural Science Youth Foundation of China (No. 81801183 and 82101376).