Free Radicals and Oxidative Stress: Signaling Mechanisms, Redox
Basis for Human Diseases, and Cell Cycle Regulation

Idris    Zubairu    Sadiq
doi:10.2174/1566524022666211222161637
Abstract

Free radicals contain one or more unpaired electrons in their valence shell, thus making them unstable, short-lived, and highly reactive species. Excessive generation of these free radicals ultimately leads to oxidative stress causing oxidation and damage to significant macromolecules in the living system and essentially disrupting signal transduction pathways and antioxidants equilibrium. At lower concentrations, ROS serves as “second messengers,” influencing many physiological processes in the cell. However, higher concentrations beyond cell capacity cause oxidative stress, contributing to human pathologies such as diabetes, cancer, Parkinson’s disease, cardiovascular diseases, cataract, asthma, hypertension, atherosclerosis, arthritis, and Alzheimer’s disease. Signaling pathways such as NF-κB, MAPKs, PI3K/Akt/ mTOR, and Keap1-Nrf2- ARE modulate the detrimental effects of oxidative stress by increasing the expression of cellular antioxidant defenses, phase II detoxification enzymes, and decreased production of ROS. Free radicals such as H2O2 are indeed needed for the advancement of the cell cycle as these molecules influence DNA, proteins, and enzymes in the cell cycle pathway. In the course of cell cycle progression, the cellular redox environment becomes more oxidized, moving from the G1 phase, becoming higher in G2/M and moderate in the S phase. Signals in the form of an increase in cellular pro-oxidant levels are required, and these signals are often terminated by a rise in the amount of antioxidants and MnSOD with a decrease in the level of cyclin D1 proteins. Therefore, understanding the mechanism of cell cycle redox regulation will help in the therapy of many diseases.
Keywords: Oxidative stress, redox signaling, reactive oxygen species, free radicals, antioxidants, redox cycle, cell cycle regulation.
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DOI https://dx.doi.org/10.2174/1566524022666211222161637	Print ISSN 1566-5240
Publisher Name Bentham Science Publisher	Online ISSN 1875-5666
Current Molecular Medicine

Free Radicals and Oxidative Stress: Signaling Mechanisms, Redox Basis for Human Diseases, and Cell Cycle Regulation

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