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Effect of SubcellularnTranslocation of Protein DisulfidenIsomerase on Tetrachlorobenzoquinone-Induced Signaling Shift fromnEndoplasmic Reticulum Stress to Apoptosis 蛋白二硫二异构酶亚细胞易位对四氯苯醌诱导的内质网应激到细胞凋亡信号转移的影响

Figshare Pub Date : 2017-09-11 DOI: 10.1021/acs.chemrestox.7b00118.s001

Zixuan Liu (475331), Yawen Wang (1578763), Yuxin Wang (414197), Wenjing Dong (117921), Xiaomin Xia (484046), Erqun Song (629771), Yang Song (1235364)

{"title":"Effect of SubcellularnTranslocation of Protein DisulfidenIsomerase on Tetrachlorobenzoquinone-Induced Signaling Shift fromnEndoplasmic Reticulum Stress to Apoptosis","authors":"Zixuan Liu (475331), Yawen Wang (1578763), Yuxin Wang (414197), Wenjing Dong (117921), Xiaomin Xia (484046), Erqun Song (629771), Yang Song (1235364)","doi":"10.1021/acs.chemrestox.7b00118.s001","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.7b00118.s001","url":null,"abstract":"Our previous studiesnillustrated tetrachlorobenzoquinone (TCBQ)-causedntoxicities in neuron-like cells which imply its association with neurodegenerativendisorders. Although it is known that TCBQ induces oxidative damagenthat in turn results in endoplasmic reticulum (ER) stress and apoptosis,nit is unclear how TCBQ triggers the signaling switch from pro-survivaln(to restore cellular homeostasis) to pro-death (trigger apoptosis).nProtein disulfide isomerase family proteins (PDIs) regulate the progressnof various neurodegenerative disorders, including Parkinson’sndisease and Alzheimer’s disease. We tested the hypothesis thatnsubcellular translocation of PDIs implicates the survival/death signalingnswitch by inducing mitochondrial outer membrane permeabilization (MOMP).nThe rat pheochromocytoma PC12 cells were exposed to TCBQ, and thenconcentration-dependent ER stress was observed upon TCBQ treatment,nas indicated by the increase in inositol-requiring kinase/endonucleasen1α (IRE1α) phosphorylation, C/EBP homologous protein (CHOP)nexpression, X-box-binding protein 1 (XBP1) splicing, and caspase 12nactivation. Interestingly, pharmacological (or siRNA) abrogation ofnPDIA1/PDIA3 aggravated the loss of cell viability induced by the relativelynlow concentration (10 μM) of TCBQ. However, inhibition of PDIA1/PDIA3nrescued the high concentration (20 μM) of TCBQ-induced cellndeath. Further mechanistic study illustrated that PDIs initially actednto restore cellular homeostasis to pro-survival but that the constantnER stress promoted the signaling switch to pro-apoptotis by the releasenof PDIA1/PDIA3 from the ER lumen to induce Bak-dependent MOMP. Ournfindings suggested that subcellular translocation of PDIs determinednthe “life or death” fate of PC12 cells to TCBQ-inducednoxidative insult.","PeriodicalId":522418,"journal":{"name":"Figshare","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147896762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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