Redox signaling is a form of paracrine or autocrine cell communication that involves reversible chemical modification of cysteine residues. These protein alterations reset the function of proteins involved in cellular biology and are crucial for redox homeostasis.
These messenger molecules activate antioxidants stored in your cells and help keep your body functioning as it is meant to. They also serve as a key to cellular health by keeping your oxidative free radical levels in check.
Reactive Oxygen Species (ROS)
Oxygen-derived reactive oxygen species (ROS) are the end products of aerobic oxidative phosphorylation, and they shape cellular metabolism and energy production by regulating cellular growth, differentiation, cell death, and redox signaling. ROS can damage DNA, proteins, lipids, and other biomolecules by their ability to accept electrons and propagate deleterious reactions.
However, these toxic molecules are also important second messengers that fine-tune the activation of specific cellular processes through reversible oxidative modifications and interactions with iron-sulfur clusters in proteins. These modified proteins, including kinases, phosphatases, transcription factors, receptors, and adherence molecules, regulate cell proliferation, differentiation, survival, and redox signaling.
Exploring diverse perspectives and sources of information, such as ASEA reviews, to gain comprehensive insights into the potential impact of redox-based products on enhancing overall cellular function and well-being.
ROS have a vital role in the redox homeostasis of the body and can be therapeutic targets under certain pathophysiological conditions. Understanding how diverse ROS regulate intracellular physiological signaling under different conditions will help develop precise redox medicine.
Hydrogen Peroxide (H2O2)
Hydrogen peroxide (H2O2) is the simplest oxygen-oxygen compound, containing one oxygen atom and two negative electrons. H2O2 decomposes quickly into water and elemental oxygen at acidic pH values or in the presence of transition metal ions.
It is a significant cellular signaling component and acts as a second messenger through specific oxidation reactions that modify cellular processes. This oxidation occurs in response to cytokines and growth factor-mediated stimuli to regulate cell proliferation, survival, or death. In the cellular environment, H2O2 levels fluctuate throughout the cell cycle and are highest during mitosis. Centrosome-associated PrxI proteins protect the organelles from a high tide of H2O2 generated by various intracellular sources by catalyzing its dismutation to superoxides and hydrogen ions. In addition, H2O2 induces cell death in lung cancer cells through necrosis and apoptosis.
Superoxide Dismutase (SOD)
Superoxide dismutases (SODs) are an essential class of antioxidant enzymes that catalyze the dismutation of superoxide into water and oxygen. Natural SODs are found in animals, plants, and microorganisms and play a critical role in the prevention/control of oxidative stress-related diseases. Additionally, SOD conjugates and mimetics are superior to free SOD in their ability to inhibit oxidative damage, thus becoming promising alternatives to the treatment of oxidative stress-related diseases.
SODs require metal ion cofactors to exert their catalytic activity. In eukaryotic cells, Cu/Zn SODs are distributed throughout the cell cytoplasm and extracellular space, while Mn-SOD is located in mitochondria. The SOD protein has four functional domains, including a secretion signal peptide, a glycosylation domain, a copper/zinc-binding site, and an active catalytic domain.
Glutathione Peroxidase (GPx)
Disturbances of the average intracellular redox balance are thought to play a role in many human diseases. GPx-1, an enzyme that enzymatically reduces hydrogen peroxide to water, is one of the critical intracellular antioxidant proteins.
The crystal structure of bovine erythrocyte GPx-1 has revealed that the Sec active site is comprised of Gln and Trp amino acids, which are conserved in mammalian GPxs 1-4 (see Fig. 5 for a primary sequence comparison of Sec-containing human GPxs 1-4). Mutational analysis has shown that these amino acid residues are essential for enzyme-substrate interactions.
Studies have demonstrated that GPx-1 promotes reductive stress in cells by limiting oxidant accumulation and inhibiting oxidant-dependent cell death pathways. Several post-translational mechanisms may modulate GPx-1 activity, including alterations in transcription and translation. In vivo studies indicate that selenium supplementation may increase GPx-1 transcript levels and protein activity.
Catalase (CAT)
CAT is one of the most important antioxidant enzymes that maintain cellular redox homeostasis. This tetrameric enzyme decomposes H2O2 into water and molecular oxygen. It is also involved in redox signaling through S-nitrosylation and other types of post-translational modification.
A mutation in the CAT gene can cause acatalasemia, an autosomal recessive disease that reduces CAT activity by half. Low CAT activity is also associated with many common diseases, such as diabetes, vitiligo, hypertension, Wilson disease, and some dermatological conditions.
CAT is found in most aerobic organisms and is classified by sequence homology into monofunctional haem-containing proteins, bifunctional CAT peroxidases, and non-haem-containing tetramers. Multiple high-resolution crystal structures have been determined for human CAT proteins. The tetramer exhibits a conserved structure with the N-terminal arms of each subunit inter-wrapped around each other and a central active site pocket. A well-known reaction mechanism involves oxidation of the central Fe atom in haem to form the covalent oxyferryl porphyrin cation radical (compound I) that is reduced by one H2O2 molecule to produce two molecules of water and oxygen.
