AhR-NQO1 Signaling in Hepatocytes Drives a Protective Response against Alcohol-induced NAD+ Depletion and Liver Damage | Chapter 05 | Recent Developments in Medicine and Medical Research Vol. 16

 ALD (alcohol-related liver disease) is one of the most common types of liver disease worldwide. It's critical to gain a better knowledge of the molecular mechanisms behind ALD in order to find new treatment targets and improve liver health. The aryl hydrocarbon receptor (AhR) is a xenobiotic receptor that is involved in the hepatic detoxification process. The function of AhRin ALD, on the other hand, is unknown. Chronic alcohol use lowered AhR expression but increased AhRand NQO1 nuclear enrichment in hepatocytes of alcoholic hepatitis (AH) humans and ALD mice, according to this study. Alcohol-induced liver injury was increased by AhR deletion, which was accompanied by a decrease in NAD(P)H quinone dehydrogenase 1 (NQO1) expression, demonstrating that NQO1 expression is dependent on AhR. Although AhR was required for NQO1 expression, NQO1 nuclear translocation was mediated by the cellular NAD+/NADH ratio rather than AhR activation. In ALD mice, nuclear NQO1 aided the operation of NAD+-dependent enzymes. Alcohol-induced hepatic NAD+ depletion was avoided and alcohol-induced liver damage was reversed when NQO1 was overexpressed. Indole-3-carbinol (I3C), a pharmaceutical that activates AhR-NQO1 signalling, reduced alcohol-induced liver damage. In conclusion, our human and mouse investigations show that AhR activation is a protective response that induces NQO1 to counterbalance alcohol-induced hepatic NAD+ depletion. Targeting the hepatic AhR-NQO1 pathway could be a unique treatment approach for ALD, according to the findings.

Author(S) Details

Haibo Dong
Center for Translational Biomedical Research, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC, USA.

Liuyi Hao
Center for Translational Biomedical Research, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC, USA.

Zhanxiang Zhou
Center for Translational Biomedical Research, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC, USA. and Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC, USA.

View Book:- https://stm.bookpi.org/RDMMR-V16/article/view/5240