Title:Free Radicals and Oxidative Stress: Signaling Mechanisms, Redox
Basis for Human Diseases, and Cell Cycle Regulation
Volume: 23
Issue: 1
Author(s): Idris Zubairu Sadiq*
Affiliation:
- Department of Biochemistry, Faculty of life Sciences, Ahmadu Bello University, Zaria-Nigeria
- Department
of Biochemistry, Faculty of Sciences, Maryam Abacha American University of Niger, ADS Avenue, Roi
Muhammad VI Du Maroc Maradi, Republique Du Niger
Keywords:
Oxidative stress, redox signaling, reactive oxygen species, free radicals, antioxidants, redox cycle, cell cycle regulation.
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.
