Genetic analysis of tissue glutathione concentrations and redox balance |
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| Institution: | 1. Department of Foods and Nutrition and University of Georgia, Athens, GA 30602, USA;2. The Jackson Laboratory, Bar Harbor, ME 04609, USA;3. Department of Statistics, University of Georgia, Athens, GA 30602, USA;4. Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA;1. College of Business Administration, Ritsumeikan University, Japan;2. Graduate School of Business Administration, Kobe University, Japan;1. Department of Biomedical and Neuromotor Sciences – DIBINEM – University of Bologna, Bologna, Italy;2. Department of Biomedical Science and Morphological and Functional Images, University of Messina, Via Consolare Valeria, 98125 Messina, Italy;1. Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Av do Cafe s/n, Ribeirao Preto, SP, Brazil;2. Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Av dos Bandeirantes, 1900, Ribeirao Preto, SP, Brazil |
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| Abstract: | Glutathione redox balance—defined as the ratio GSH/GSSG—is a critical regulator of cellular redox state, and declines in this ratio are closely associated with oxidative stress and disease. However, little is known about the impact of genetic variation on this trait. Previous mouse studies suggest that tissue GSH/GSSG is regulated by genetic background and is therefore heritable. In this study, we measured glutathione concentrations and GSH/GSSG in liver and kidney of 30 genetically diverse inbred mouse strains. Genetic background caused an approximately threefold difference in hepatic and renal GSH/GSSG between the most disparate strains. Haplotype association mapping determined the loci associated with hepatic and renal glutathione phenotypes. We narrowed the number of significant loci by focusing on those located within protein-coding genes, which we now consider to be candidate genes for glutathione homeostasis. No candidate genes were associated with both hepatic and renal GSH/GSSG, suggesting that genetic regulation of GSH/GSSG occurs predominantly in a tissue-specific manner. This is the first quantitative trait locus study to examine the genetic regulation of glutathione concentrations and redox balance in mammals. We identified novel candidate genes that have the potential to redefine our knowledge of redox biochemistry and its regulation and inform future therapeutic applications. |
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| Keywords: | Glutathione Genetics Redox Mice Free radicals |
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