Preprint Article Version 1 This version is not peer-reviewed

The Role of Golgi Morphology in Post-Alcohol Recovery of Hepatocytes: Observations in Cellular and Animal Models

Version 1 : Received: 22 October 2018 / Approved: 23 October 2018 / Online: 23 October 2018 (06:10:04 CEST)

A peer-reviewed article of this Preprint also exists.

Casey, C.A.; Thomes, P.; Manca, S.; Petrosyan, A. Giantin Is Required for Post-Alcohol Recovery of Golgi in Liver Cells. Biomolecules 2018, 8, 150. Casey, C.A.; Thomes, P.; Manca, S.; Petrosyan, A. Giantin Is Required for Post-Alcohol Recovery of Golgi in Liver Cells. Biomolecules 2018, 8, 150.

Journal reference: Biomolecules 2018, 8, 150
DOI: 10.3390/biom8040150

Abstract

Background: In hepatocytes and alcohol-metabolizing cultured cells, Golgi undergoes ethanol (EtOH)-induced disorganization. Periniclear and organized Golgi is important in liver homeostasis, but how the Golgi remains intact is unknown. Work from our laboratories showed that EtOH-altered cellular function could be reversed after alcohol removal; we wanted to determine whether this recovery would apply to Golgi. Methods: We used alcohol-metabolizing HepG2 (VA-13) cells (cultured with or without EtOH for 72 h) and rat hepatocytes (control and EtOH-fed (Lieber-DeCarli diet). For recovery, EtOH was removed and replenished with control medium (48 hours for VA-13 cells) or control diet (10 days for rats). Results: EtOH-induced Golgi disassembly was associated with de-dimerization of the largest Golgi matrix protein giantin, along with impaired transport of selected hepatic proteins. After recovery from EtOH, Golgi regained their compact structure, and alterations in giantin and protein transport were restored. In VA-13 cells, when we knocked down giantin, Rab6a GTPase or non-muscle Myosin IIB, minimal changes were observed in control conditions, but post-EtOH recovery was impaired. Conclusions: These data provide a link between Golgi organization and plasma membrane protein expression and identify several proteins whose expression is important to maintain Golgi structure during the recovery phase after EtOH administration.

Subject Areas

alcohol-induced Golgi disorganization; Golgi recovery; giantin; hepatic proteins; ethanol withdrawal

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