Stress Induction and Mitochondrial Localization of Oxr1 Proteins in Yeast and Humans
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.
[Show abstract] [Hide abstract] ABSTRACT: Abstract Since the last decade, nanodispersed drug delivery systems gain increasingly more importance for therapeutic research fields. The forced transport to the centers of inflammation is supposed to take advantage as a novel strategic approach. Thus, the focus of this study was to investigate the applicability of ubiquinone nanoformulations against oxidative stress. The physiological reduction of reactive oxygen species (ROS) seems to be a promising treatment to point out the potential effects of these sophisticated nano-constructs. Therefore, the yeast strain Saccharomyces cerevisiae N34 was used for in vitro studies as a representative for eukaryotic organisms. Growth parameters during sequential fed batch-cultivation were monitored online using focused beam reflectance measurement (FBRM) method. The ability to control diverse cellular processes makes this yeast strain to a valuable tool for the initial investigation by understanding the fundamental mechanisms of nanoparticulate formulations onto eukaryotic cells. Furthermore, the characteristic stress response of yeast cell culture was examined, so that drug effects could be determined quantitatively. As a chemical stressor, diamide was tested in the range of 1–1000 mg diamide per g cell dry weight (CDW). The ubiquinone nanoformulation demonstrated a total stress reduction of approximately 14% in the yeast culture, confirming the potential applicability of ubiquinone.0Comments 0Citations
- "Yeast mutants with an OXR1 deletion exhibit increased sensitivity to H 2 O 2 (Volkert et al., 2000 ). Based on the importance of OXR1 during stress, a GFPencoding gene was integrated into the promoter of OXR1 in S. cerevisiae N34 (Elliott and Volkert, 2004). Consequently, ROS enrichment results in GFP fluorescence due to the activation of OXR1 gene expression, which thus functions as a direct indicator of oxidative stress (Vandenbroucke et al., 2008). "
[Show abstract] [Hide abstract] 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.0Comments 5Citations
- "The role of OXR1 in preventing oxidative stress-induced cell death has been previously addressed in yeast, mosquito and mice    . Expression of truncated human OXR1 in yeast reversed H 2 O 2 sensitivity in yeast oxr1 mutant, suggesting a similar function in human . 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. "
[Show abstract] [Hide abstract] 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.0Comments 7Citations
- "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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