Disrupted ER-to-Golgi Trafficking Underlies Anti-HIV Drugs and Alcohol-Induced Cellular Stress and Hepatic Injury.

ABSTRACT: Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are involved in anti-human immunodeficiency virus (HIV) drugs and alcohol-induced 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-boosted 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-treated cells, ATF6 localization in the Golgi apparatus required for its activation was reduced; this was followed by Golgi fragmentation and dislocation/redistribution of Golgi-resident enzymes. Severities of Golgi fragmentation induced by other a

SUBMITTER: Han H 

PROVIDER: S-EPMC5473515 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature