Dataset Information

Parkin deficiency prevents chronic ethanol-induced hepatic lipid accumulation through ?-catenin accumulation.

ABSTRACT:

Background

Alcohol abuse and alcoholism lead to alcohol liver disease such as alcoholic fatty liver. Parkin is a component of the multiprotein E3 ubiquitin ligase complex and is associated with hepatic lipid accumulation. However, the role of parkin in ethanol-induced liver disease has not been reported. Here, we tested the effect of parkin on ethanol-induced fatty liver in parkin knockout (KO) mice with chronic ethanol feeding.

Methods

Male wild type (WT) and parkin KO mice (10-12?weeks old, n =?10) were fed on a Lieber-DeCarli diet containing 6.6% ethanol for 10?days. Liver histological, biochemical, and gene-expression studies were performed.

Results

Parkin KO mice exhibited lower hepatosteatosis after ethanol consumption. Because several studies reported that ?-catenin is a critical factor in ethanol metabolism and protects against alcohol-induced hepatosteatosis, we investigated whether parkin changes ?-catenin accumulation in the liver of ethanol-fed mice. Our results show that ?-catenin was greatly accumulated in the livers of ethanol-fed parkin KO mice compared to ethanol-fed WT mice, and that parkin binds to ?-catenin and promotes its degradation it by ubiquitination. Moreover, the ?-catenin inhibitor IWR-1 abrogated the attenuation of ethanol-induced hepatic lipid accumulation by parkin deficiency in the livers of parkin KO mice and parkin siRNA-transfected human hepatic cell line.

Conclusions

Parkin deficiency prevents ethanol-induced hepatic lipid accumulation through promotion of ?-catenin signaling by failure of ?-catenin degradation.

SUBMITTER: Lee DH

PROVIDER: S-EPMC6704582 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Parkin deficiency prevents chronic ethanol-induced hepatic lipid accumulation through β-catenin accumulation.

Lee Dong Hun DH Park Mi Hee MH Hwang Chul Ju CJ Kim Youngsoo Y Hwang Dae Yeon DY Han Sang Bae SB Hong Jin Tae JT

Cell communication and signaling : CCS 20190822 1

<h4>Background</h4>Alcohol abuse and alcoholism lead to alcohol liver disease such as alcoholic fatty liver. Parkin is a component of the multiprotein E3 ubiquitin ligase complex and is associated with hepatic lipid accumulation. However, the role of parkin in ethanol-induced liver disease has not been reported. Here, we tested the effect of parkin on ethanol-induced fatty liver in parkin knockout (KO) mice with chronic ethanol feeding.<h4>Methods</h4>Male wild type (WT) and parkin KO mice (10-1 ...[more]

PMID: 31438968

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