iTRAQ-derived quantitative proteomics uncovers the neuroprotective property of bexarotene in a mice model of cerebral ischemia-reperfusion injury

作者全名："Liu, Hailin; Wang, Hu; Chen, Sisi; Liu, Shengwei; Tian, Xiaocui; Dong, Zhi; Xu, Lu"

作者地址："[Liu, Hailin; Wang, Hu] First Peoples Hosp Chongqing Liangjiang New Area, Dept Pharm, Chongqing 401121, Peoples R China; [Chen, Sisi] Chongqing Med & Pharmaceut Coll, Sch Clin Med, Chongqing, Peoples R China; [Liu, Shengwei; Tian, Xiaocui; Dong, Zhi] Chongqing Med Univ, Dept Pharmacol, Key Lab Biochem & Mol Pharmacol, Chongqing 400016, Peoples R China; [Xu, Lu] Chongqing Med & Pharmaceut Coll, Sch Pharm, Chongqing 41331, Peoples R China"

通信作者："Xu, L (通讯作者)，Chongqing Med & Pharmaceut Coll, Dept Pharmacol, Chongqing 401331, Peoples R China."

来源：SAUDI PHARMACEUTICAL JOURNAL

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000814068700010

JCR分区：Q1

影响因子：4.1

年份：2022

卷号：30

期号：5

开始页：585

结束页：594

文献类型：Article

关键词：Bexarotene; Cerebral ischemia reperfusion injury; iTRAQ; Apoptosis; JIP3

摘要："Bexarotene, a FDA-approved drug for cutaneous lymphoma, has been shown to exert brain protective effects. In previous study, we demonstrated that Bexarotene protects against cerebral ischemic stroke by suppressing the JNK/Caspase-3 signaling pathway. However, the molecular mechanisms by which Bexarotene-mediated neuroprotective are not fully understood. Based on the isobaric tags for relative and absolute quantification (iTRAQ)-derived proteomics and bioinformatics analysis, 4,454 differentially expressed proteins (DEPs) were identified in upstream of the JNK signaling pathway. Among them, 149 DEPs showed aberrant expression in the vehicle-versus Bexarotene-treated mice. DEPs were primarily enriched in the metabolism, calcium, and MAPK signaling pathways. The largest DEP increase was seen with heat shock protein HSP 70, whereas the largest DEP decrease was seen with JNK scaffold protein JIP3, both of which are involved in the MAPK network. Furthermore, we illustrated the Bexarotene obviously abolished oxygen and glucose deprivation/reperfusion (OGD/R)- induced LDH leakage, cells apoptosis, and the protein expression level of the JIP3,p-ASK1, p-JNK, and Cleaved Caspase3. Together, these results suggest a potential neuroprotective role of Bexarotene via inhibition of the JIP3/ASK1/JNK/Caspase 3 signaling pathway. (C) 2022 The Authors. Published by Elsevier B.V. on behalf of King Saud University."

基金机构：Chongqing Science Technology Commission of China [cstc2019jscx-msxmX0096]

基金资助正文：This study was supported by research grants from the Chongqing Science Technology Commission of China (NO: cstc2019jscx-msxmX0096) .