Format

Send to

Choose Destination
Sci Rep. 2017 Aug 21;7(1):8976. doi: 10.1038/s41598-017-02759-0.

Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice.

Author information

1
Center for Translational Biomedical Research, University of North Carolina Greensboro, North Carolina Research Campus, Kannapolis, NC, 28081, USA.
2
Center for Translational Biomedical Research, University of North Carolina Greensboro, North Carolina Research Campus, Kannapolis, NC, 28081, USA. z_zhou@uncg.edu.
3
Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC, 28081, USA. z_zhou@uncg.edu.

Abstract

Chronic alcohol feeding causes lipid accumulation and apoptosis in the liver. This study investigated the role of bioactive lipid metabolites in alcohol-induced liver damage and tested the potential of targeting arachidonate 15-lipoxygenase (ALOX15) in treating alcoholic liver disease (ALD). Results showed that chronic alcohol exposure induced hepatocyte apoptosis in association with increased hepatic 13-HODE. Exposure of 13-HODE to Hepa-1c1c7 cells induced oxidative stress, ER stress and apoptosis. 13-HODE also perturbed proteins related to lipid metabolism. HODE-generating ALOX15 was up-regulated by chronic alcohol exposure. Linoleic acid, but not ethanol or acetaldehyde, induced ALOX15 expression in Hepa-1c1c7 cells. ALOX15 knockout prevented alcohol-induced liver damage via attenuation of oxidative stress, ER stress, lipid metabolic disorder, and cell death signaling. ALOX15 inhibitor (PD146176) treatment also significantly alleviated alcohol-induced oxidative stress, lipid accumulation and liver damage. These results demonstrated that activation of ALOX15/13-HODE circuit critically mediates the pathogenesis of ALD. This study suggests that ALOX15 is a potential molecular target for treatment of ALD.

PMID:
28827690
PMCID:
PMC5567196
DOI:
10.1038/s41598-017-02759-0
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center