CHOP Regulates Endoplasmic Reticulum Stress-Mediated Hepatoxicity Induced by Monocrotaline

• DOI: 10.3389/fphar.2021.685895
• Publication Date: 2021-05-24T06:38:42Z
• Authors: Yazhou Guo; Chen Yang; Rong Guo; Ruijie Huang; Yongxia Su; Shuai Wang; Yezi Kong; Jianguo Wang; Chengjian Tan; Chonghui Mo; Chenchen Wu; Baoyu Zhao
• Keywords: ATF6; Viability assay; Thapsigargin

Monocrotaline (MCT), a pyrrolizidine alkaloid, is the major toxin in Crotalaria , which causes cell apoptosis humans and animals. It has been reported that liver vulnerable target of MCT. However, exact molecular mechanism interaction between endoplasmic reticulum (ER) stress injury induced by MCT still unclear. In this study, cytotoxicity on primary rat hepatocytes was analyzed CCK-8 assay Annexin V-FITC/PI assay. Protein expression detected western blotting immunofluorescence staining. As result, significantly decreased viability mediated hepatocytes. Meanwhile, could also induce ER hepatocytes, indicated stress-related proteins, including GRP78, p-IRE1α, ATF6, p-eIF2α, ATF4, CHOP. Pretreatment with 4-PBA, an inhibitor stress, or knockdown CHOP siRNA partly enhance relieve apoptosis. Our findings indicate involved hepatotoxicity MCT, plays important role process.