Prxs are a family of thiol-dependent antioxidants that can scavenge cytosolic or mitochondrial peroxides. Trxs can catalyze the reversible reduction of protein disulfide bonds using redox-active cysteine residues in their active site. Thus, they have become targets for redox modifications. Therefore, the oxidative modification of PTEN contributes to augmenting PIP3 levels, resulting in the activation of the PI3K/AKT signaling pathway and protecting cells from oxidative stress-induced cell death.Įndogenous antioxidants, such as thioredoxins (Trxs) and peroxiredoxins (Prxs), can modulate ROS levels and intracellular redox state. Numerous studies have demonstrated that the catalytic activity of PTEN is modulated by ROS, subsequently resulting in its catalytic inhibition. PTEN is a nonredundant, plasma-membrane lipid phosphatase that can antagonize PI3K by dephosphorylating PIP3 at position D3 to generate PIP2. Upon the activation of cells by growth stimuli, classic PI3K family members catalyze the phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3), a potent activator of 3-phosphoinositide-dependent kinase (PDK) and AKT. It has been shown that external stimuli, such as insulin, cytokines, neurotransmitters, peptide growth factors, and hormones, can activate the PI3K pathway, which results in ROS generation, , ]. The interaction of growth factors with receptor tyrosine kinases (RTK) typically activates PI3K. Signaling through PI3K/AKT is pivotal to cell growth and survival. Because of the lack of enzymes to remove hydroxyl radicals and reactive aldehydes, their aggressive reactivity leads to the irreversible oxidation or degradation of functional proteins, a mechanism underlying various disorders and pathologies, such as diabetes, obesity, and cancer. To function as signaling messengers, these reactive molecules mainly trigger reversible oxidative post-translational modifications (PTMs) of reactive cysteine residues in regulatory proteins. Increasing evidence has indicated that ROS, such as H 2O 2, are produced and employed in physiological settings to serve as important signaling messengers for coordinating a variety of physiological functions, including proliferation, differentiation, apoptosis, signal transduction, and other critical events, ,, ]. Reactive oxygen species (ROS) are inevitably generated during aerobic and anaerobic metabolism and have detrimental effects on cellular biomolecules under pathological conditions.
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