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      ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells

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          Abstract

          Reactive oxygen species (ROS) are by-products of normal cell activity. They are produced in many cellular compartments and play a major role in signaling pathways. Overproduction of ROS is associated with the development of various human diseases (including cancer, cardiovascular, neurodegenerative, and metabolic disorders), inflammation, and aging. Tumors continuously generate ROS at increased levels that have a dual role in their development. Oxidative stress can promote tumor initiation, progression, and resistance to therapy through DNA damage, leading to the accumulation of mutations and genome instability, as well as reprogramming cell metabolism and signaling. On the contrary, elevated ROS levels can induce tumor cell death. This review covers the current data on the mechanisms of ROS generation and existing antioxidant systems balancing the redox state in mammalian cells that can also be related to tumors.

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          On the origin of cancer cells.

          O WARBURG (1956)
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            TIGAR, a p53-Inducible Regulator of Glycolysis and Apoptosis

            The p53 tumor-suppressor protein prevents cancer development through various mechanisms, including the induction of cell-cycle arrest, apoptosis, and the maintenance of genome stability. We have identified a p53-inducible gene named TIGAR (TP53-induced glycolysis and apoptosis regulator). TIGAR expression lowered fructose-2,6-bisphosphate levels in cells, resulting in an inhibition of glycolysis and an overall decrease in intracellular reactive oxygen species (ROS) levels. These functions of TIGAR correlated with an ability to protect cells from ROS-associated apoptosis, and consequently, knockdown of endogenous TIGAR expression sensitized cells to p53-induced death. Expression of TIGAR may therefore modulate the apoptotic response to p53, allowing survival in the face of mild or transient stress signals that may be reversed or repaired. The decrease of intracellular ROS levels in response to TIGAR may also play a role in the ability of p53 to protect from the accumulation of genomic damage.
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              The endoplasmic reticulum: structure, function and response to cellular signaling

              The endoplasmic reticulum (ER) is a large, dynamic structure that serves many roles in the cell including calcium storage, protein synthesis and lipid metabolism. The diverse functions of the ER are performed by distinct domains; consisting of tubules, sheets and the nuclear envelope. Several proteins that contribute to the overall architecture and dynamics of the ER have been identified, but many questions remain as to how the ER changes shape in response to cellular cues, cell type, cell cycle state and during development of the organism. Here we discuss what is known about the dynamics of the ER, what questions remain, and how coordinated responses add to the layers of regulation in this dynamic organelle.
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                Author and article information

                Contributors
                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OMCL
                Oxidative Medicine and Cellular Longevity
                Hindawi
                1942-0900
                1942-0994
                2019
                5 August 2019
                : 2019
                : 6175804
                Affiliations
                Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
                Author notes

                Academic Editor: Maria Isaguliants

                Author information
                https://orcid.org/0000-0002-4421-4364
                https://orcid.org/0000-0002-3722-8207
                https://orcid.org/0000-0002-5593-7867
                https://orcid.org/0000-0001-8083-3018
                https://orcid.org/0000-0002-6493-8378
                https://orcid.org/0000-0002-6827-9584
                Article
                10.1155/2019/6175804
                6701375
                31467634
                61ef6116-379f-4429-8d37-d6d2356d6bba
                Copyright © 2019 Anastasiya V. Snezhkina et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 5 April 2019
                : 24 June 2019
                Funding
                Funded by: Russian Science Foundation
                Award ID: 17-74-20064
                Award ID: 17-75-20105
                Categories
                Review Article

                Molecular medicine
                Molecular medicine

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