Article

Stress Induction and Mitochondrial Localization of Oxr1 Proteins in Yeast and Humans

Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Molecular and Cellular Biology (Impact Factor: 5.04). 05/2004; 24(8):3180-7. DOI: 10.1128/MCB.24.8.3180-3187.2004
Source: PubMed

ABSTRACT Reactive oxygen species (ROS) are critical molecules produced as a consequence of aerobic respiration. It is essential for cells to control the production and activity of such molecules in order to protect the genome and regulate cellular processes such as stress response and apoptosis. Mitochondria are the major source of ROS within the cell, and as a result, numerous proteins have evolved to prevent or repair oxidative damage in this organelle. The recently discovered OXR1 gene family represents a set of conserved eukaryotic genes. Previous studies of the yeast OXR1 gene indicate that it functions to protect cells from oxidative damage. In this report, we show that human and yeast OXR1 genes are induced by heat and oxidative stress and that their proteins localize to the mitochondria and function to protect against oxidative damage. We also demonstrate that mitochondrial localization is required for Oxr1 protein to prevent oxidative damage.

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    • "The role of OXR1 in preventing oxidative stress-induced cell death has been previously addressed in yeast, mosquito and mice [7] [8] [14] [15]. Expression of truncated human OXR1 in yeast reversed H 2 O 2 sensitivity in yeast oxr1 mutant, suggesting a similar function in human [6]. In this paper, based on the hOXR1 knock-down experiments in several human cell lines, we demonstrated that OXR1 has the same anti-oxidation function in human cells as observed in model organisms. "
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    ABSTRACT: The oxidation resistance gene 1 (OXR1) prevents oxidative stress-induced cell death by an unknown pathway. Here, depletion of human OXR1 (hOXR1) sensitized several human cell lines to hydrogen peroxide-induced oxidative stress, reduced mtDNA integrity, and increased apoptosis. In contrast, depletion of hOXR1 in cells lacking mtDNA showed no significant change in ROS or viability, suggesting that OXR1 prevents intracellular hydrogen peroxide-induced increase in oxidative stress levels to avoid a vicious cycle of increased oxidative mtDNA damage and ROS formation. Furthermore, expression of p21 and the antioxidant genes GPX2 and HO-1 was reduced in hOXR1-depleted cells. In sum, these data reveal that human OXR1 upregulates the expression of antioxidant genes via the p21 signaling pathway to suppress hydrogen peroxide-induced oxidative stress and maintain mtDNA integrity.
    Free Radical Biology and Medicine 09/2014; 77. DOI:10.1016/j.freeradbiomed.2014.09.003 · 5.71 Impact Factor
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    • "OXR1 is an oxidation resistant protein. Yeast oxr1 mutant is sensitive to H2O2.(44) Expression of human OXR1 complements the frequency of spontaneous mutations in base excision repair-deficient E. coli.(44) "
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    ABSTRACT: Excessive generation of reactive oxygen species within cells results in oxidative stress. Furthermore, accumulation of reactive oxygen species has been shown to reduce cell longevity. Many dietary supplements are believed to have anti-aging effects. The herb mixture KPG-7 contains several components with antioxidant activity. We aim to clarify the mechanisms responsible for the antioxidant activity of KPG-7 and to establish whether KPG-7 has an anti-aging effect. We examined whether dietary supplementation with KPG-7 could provide protection against oxidative stress, extend lifespan, and delay aging in Caenorhabditis elegans (C. elegans). We found that KPG-7 extended lifespan and delayed aging in adult C. elegans. The expression of oxidation resistance 1 protein was induced by juglone and this effect was significantly suppressed in KPG-7-treated. In addition, the amount of oxidized protein was significantly lower in KPG-7-treated worms than untreated worms. Furthermore, locomotive activity was increased in C. elegans at 3 days of age following the treatment with KPG-7. On the other hand, the level of cellular ATP was lower at 3 days of age in worms treated with KPG-7 than in untreated worms. KPG-7 increases lifespan and delays aging in C. elegans, well corresponding to its activity to protect against oxidative stress.
    Journal of Clinical Biochemistry and Nutrition 09/2013; 53(2):81-8. DOI:10.3164/jcbn.13-11 · 2.29 Impact Factor
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    • "We obtained a set of 387 genes, including all genes previously investigated in candidate GxE interaction studies in respiratory epidemiology such as MPO, CAT, GCLM, GCLC, GSTP1, NQO1[15-21], and some genes in the study by Polonikov et al. [12]. We further enlarged the gene set by using our own expertise, GWAS literature reviews, and biological studies [22-26]. A total of 411 genes were then considered for the next step. "
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    ABSTRACT: The identification of gene by environment (GxE) interactions has emerged as a challenging but essential task to fully understand the complex mechanism underlying multifactorial diseases. Until now, GxE interactions have been investigated by candidate approaches examining a small number of genes, or agnostically at the genome wide level. In this paper, we propose a gene selection strategy for investigation of gene-environment interactions. This strategy integrates the information on biological processes shared by genes, the canonical pathways to which they belong and the biological knowledge related to the environment in the gene selection process. It relies on both bioinformatics resources and biological expertise. We illustrate our strategy by considering asthma, tobacco smoke as the environmental exposure, and genes sharing the same biological function of "response to oxidative stress". Our filtering strategy leads to a list of 12 pathways involving 104 genes for further GxE investigation. By integrating the environment into the gene selection process, we expect that our strategy will improve the ability to identify the joint effects and interactions of environmental and genetic factors in disease.
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