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      Oxidative Stress and Programmed Cell Death in Yeast


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          Yeasts, such as Saccharomyces cerevisiae, have long served as useful models for the study of oxidative stress, an event associated with cell death and severe human pathologies. This review will discuss oxidative stress in yeast, in terms of sources of reactive oxygen species (ROS), their molecular targets, and the metabolic responses elicited by cellular ROS accumulation. Responses of yeast to accumulated ROS include upregulation of antioxidants mediated by complex transcriptional changes, activation of pro-survival pathways such as mitophagy, and programmed cell death (PCD) which, apart from apoptosis, includes pathways such as autophagy and necrosis, a form of cell death long considered accidental and uncoordinated. The role of ROS in yeast aging will also be discussed.

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          Genomic expression programs in the response of yeast cells to environmental changes.

          We explored genomic expression patterns in the yeast Saccharomyces cerevisiae responding to diverse environmental transitions. DNA microarrays were used to measure changes in transcript levels over time for almost every yeast gene, as cells responded to temperature shocks, hydrogen peroxide, the superoxide-generating drug menadione, the sulfhydryl-oxidizing agent diamide, the disulfide-reducing agent dithiothreitol, hyper- and hypo-osmotic shock, amino acid starvation, nitrogen source depletion, and progression into stationary phase. A large set of genes (approximately 900) showed a similar drastic response to almost all of these environmental changes. Additional features of the genomic responses were specialized for specific conditions. Promoter analysis and subsequent characterization of the responses of mutant strains implicated the transcription factors Yap1p, as well as Msn2p and Msn4p, in mediating specific features of the transcriptional response, while the identification of novel sequence elements provided clues to novel regulators. Physiological themes in the genomic responses to specific environmental stresses provided insights into the effects of those stresses on the cell.
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            Role of reactive oxygen species (ROS) in apoptosis induction.

            Reactive oxygen species (ROS) and mitochondria play an important role in apoptosis induction under both physiologic and pathologic conditions. Interestingly, mitochondria are both source and target of ROS. Cytochrome c release from mitochondria, that triggers caspase activation, appears to be largely mediated by direct or indirect ROS action. On the other hand, ROS have also anti-apoptotic effects. This review focuses on the role of ROS in the regulation of apoptosis, especially in inflammatory cells.
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              Oxidants, antioxidants, and the degenerative diseases of aging.

              Metabolism, like other aspects of life, involves tradeoffs. Oxidant by-products of normal metabolism cause extensive damage to DNA, protein, and lipid. We argue that this damage (the same as that produced by radiation) is a major contributor to aging and to degenerative diseases of aging such as cancer, cardiovascular disease, immune-system decline, brain dysfunction, and cataracts. Antioxidant defenses against this damage include ascorbate, tocopherol, and carotenoids. Dietary fruits and vegetables are the principal source of ascorbate and carotenoids and are one source of tocopherol. Low dietary intake of fruits and vegetables doubles the risk of most types of cancer as compared to high intake and also markedly increases the risk of heart disease and cataracts. Since only 9% of Americans eat the recommended five servings of fruits and vegetables per day, the opportunity for improving health by improving diet is great.

                Author and article information

                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Research Foundation
                20 June 2012
                : 2
                : 64
                [1] 1simpleDepartment of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta Msida, Malta
                Author notes

                Edited by: Frank Madeo, Karl-Franzens-Universitat Graz, Austria

                Reviewed by: Michael Breitenbach, University of Salzburg, Austria; Ian Dawes, University of New South Wales, Australia

                *Correspondence: Rena Balzan, Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida MSD 2080, Malta. e-mail: rena.balzan@ 123456um.edu.mt

                This article was submitted to Frontiers in Molecular and Cellular Oncology, a specialty of Frontiers in Oncology.

                Copyright © 2012 Farrugia and Balzan.

                This is an openaccess article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.

                : 03 April 2012
                : 02 June 2012
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 344, Pages: 21, Words: 23118
                Review Article

                Oncology & Radiotherapy
                yeast,apoptosis,autophagy,mitophagy,oxidative stress,aging,necrosis
                Oncology & Radiotherapy
                yeast, apoptosis, autophagy, mitophagy, oxidative stress, aging, necrosis


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