{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:08:41Z","timestamp":1791515321824,"version":"4.3.4"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2017,3,27]],"date-time":"2017-03-27T00:00:00Z","timestamp":1490572800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Communications"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:p>\n                    Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are involved in anti\u2010human immunodeficiency virus (HIV) drugs and alcohol\u2010induced liver disease in a significant number of patients infected with HIV. However, the precise mechanism by which the drugs and alcohol cause ER stress remains elusive. We found that ritonavir\u2010boosted lopinavir (RL) activated two canonical UPR branches without activation of the third canonical activating transcription factor 6 (ATF6) branch in either HepG2 cells or primary mouse hepatocytes. In the RL\u2010treated cells, ATF6 localization in the Golgi apparatus required for its activation was reduced; this was followed by Golgi fragmentation and dislocation\/redistribution of Golgi\u2010resident enzymes. Severities of Golgi fragmentation induced by other anti\u2010HIV drugs varied and were correlated with the ER stress response. In the liver of mice fed RL, alcohol feeding deteriorated the Golgi fragmentation, which was correlated with ER stress, elevated alanine aminotransferase, and liver steatosis. The Golgi stress response (GSR) markers GCP60 and HSP47 were increased in RL\u2010treated liver cells, and knockdown of transcription factor for immunoglobulin heavy\u2010chain enhancer 3 of the GSR by small interfering RNA worsened RL\u2010induced cell death. Cotreatment of pharmacological agent H89 with RL inhibited the RL\u2010induced Golgi enzyme dislocation and ER stress. Moreover, the coat protein complex II (COPII) complexes that mediate ER\u2010to\u2010Golgi trafficking accumulated in the RL\u2010treated liver cells; this was not due to interference of RL with the initial assembly of the COPII complexes. RL also inhibited Golgi fragmentation and reassembly induced by short treatment and removal of brefeldin A.\n                    <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    : Our study indicates that ER\u2010to\u2010Golgi trafficking is disrupted by anti\u2010HIV drugs and\/or alcohol, and this contributes to subsequent ER stress and hepatic injury. (\n                    <jats:italic toggle=\"yes\">Hepatology Communications<\/jats:italic>\n                    2017;1:122\u2010139)\n                  <\/jats:p>","DOI":"10.1002\/hep4.1030","type":"journal-article","created":{"date-parts":[[2017,3,27]],"date-time":"2017-03-27T07:55:33Z","timestamp":1490601333000},"page":"122-139","source":"Crossref","is-referenced-by-count":26,"title":["Disrupted ER\u2010to\u2010Golgi trafficking underlies anti\u2010HIV drugs and alcohol\u2010induced cellular stress and hepatic injury"],"prefix":"10.1097","volume":"1","author":[{"given":"Hui","family":"Han","sequence":"first","affiliation":[{"name":"GI\/Liver Division, Department of Medicine, Keck School of Medicine,University of Southern California,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"He","sequence":"additional","affiliation":[{"name":"GI\/Liver Division, Department of Medicine, Keck School of Medicine,University of Southern California,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Hu","sequence":"additional","affiliation":[{"name":"GI\/Liver Division, Department of Medicine, Keck School of Medicine,University of Southern California,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhema","family":"Lau","sequence":"additional","affiliation":[{"name":"GI\/Liver Division, Department of Medicine, Keck School of Medicine,University of Southern California,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harrison","family":"Lee","sequence":"additional","affiliation":[{"name":"GI\/Liver Division, Department of Medicine, Keck School of Medicine,University of Southern California,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Ji","sequence":"additional","affiliation":[{"name":"GI\/Liver Division, Department of Medicine, Keck School of Medicine,University of Southern California,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2017,3,27]]},"reference":[{"key":"hep41030-bib-0001-20240114","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1126\/science.1256739","article-title":"HIV epidemiology. 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