Document Type

Article

Publication Date

8-5-2021

Publication Title

Redox Biol

Keywords

JMG

JAX Source

Redox Biol 2021 Aug 5; 46:102093

Volume

46

First Page

102093

Last Page

102093

ISSN

2213-2317

PMID

34418604

DOI

https://doi.org/10.1016/j.redox.2021.102093

Abstract

The tripeptide glutathione (GSH) is instrumental to antioxidant protection and xenobiotic metabolism, and the ratio of its reduced and oxidized forms (GSH/GSSG) indicates the cellular redox environment and maintains key aspects of cellular signaling. Disruptions in GSH levels and GSH/GSSG have long been tied to various chronic diseases, and many studies have examined whether variant alleles in genes responsible for GSH synthesis and metabolism are associated with increased disease risk. However, past studies have been limited to established, canonical GSH genes, though emerging evidence suggests that novel loci and genes influence the GSH redox system in specific tissues. The present study marks the most comprehensive effort to date to directly identify genetic loci associated with the GSH redox system. We employed the Diversity Outbred (DO) mouse population, a model of human genetics, and measured GSH and the essential redox cofactor NADPH in liver, the organ with the highest levels of GSH in the body. Under normal physiological conditions, we observed substantial variation in hepatic GSH and NADPH levels and their redox balances, and discovered a novel, significant quantitative trait locus (QTL) on murine chromosome 16 underlying GSH/GSSG; bioinformatics analyses revealed Socs1 to be the most likely candidate gene. We also discovered novel QTL associated with hepatic NADP

Comments

The authors gratefully acknowledge Greg Keele, Vivek Phillip, Belinda Cornes, and Dan Gatti for their assistance with the genetic mapping process, Kim Love for her help with statistical calculations, Kristen Peissig, Mallory Johns, Kylah Chase, Aida Rassam, Tina Heydari, Lynsey Young, and Madeleine Williams for their assistance with the data collection, and Ali Ennis for creating the graphical abstract.

This article is licensed under a Creative Commons Attribution 4.0 International License.

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