Trinh, V.H.; Choi, J.-M.; Nguyen Huu, T.; Sah, D.K.; Yoon, H.-J.; Park, S.-C.; Jung, Y.-S.; Ahn, Y.-K.; Lee, K.-H.; Lee, S.-R. Redox Regulation of Phosphatase and Tensin Homolog by Bicarbonate and Hydrogen Peroxide: Implication of Peroxymonocarbonate in Cell Signaling. Antioxidants2024, 13, 473.
Trinh, V.H.; Choi, J.-M.; Nguyen Huu, T.; Sah, D.K.; Yoon, H.-J.; Park, S.-C.; Jung, Y.-S.; Ahn, Y.-K.; Lee, K.-H.; Lee, S.-R. Redox Regulation of Phosphatase and Tensin Homolog by Bicarbonate and Hydrogen Peroxide: Implication of Peroxymonocarbonate in Cell Signaling. Antioxidants 2024, 13, 473.
Trinh, V.H.; Choi, J.-M.; Nguyen Huu, T.; Sah, D.K.; Yoon, H.-J.; Park, S.-C.; Jung, Y.-S.; Ahn, Y.-K.; Lee, K.-H.; Lee, S.-R. Redox Regulation of Phosphatase and Tensin Homolog by Bicarbonate and Hydrogen Peroxide: Implication of Peroxymonocarbonate in Cell Signaling. Antioxidants2024, 13, 473.
Trinh, V.H.; Choi, J.-M.; Nguyen Huu, T.; Sah, D.K.; Yoon, H.-J.; Park, S.-C.; Jung, Y.-S.; Ahn, Y.-K.; Lee, K.-H.; Lee, S.-R. Redox Regulation of Phosphatase and Tensin Homolog by Bicarbonate and Hydrogen Peroxide: Implication of Peroxymonocarbonate in Cell Signaling. Antioxidants 2024, 13, 473.
Abstract
Phosphatase and tensin homolog (PTEN) is a negative regulator of the phosphoinositide 3-kinases/protein kinase B (PI3K/AKT) signaling pathway. Notably, its active site harbors a cysteine residue that is susceptible to oxidation by hydrogen peroxide (H2O2). This oxidation inhibits the phosphatase function of PTEN, critically contributing to the activation of the PI3K/AKT pathway. Upon stimulation of cell surface receptors, the activity of NADPH oxidase 2 (NOX2) generates a transient amount of H2O2, serving as a mediator in this pathway by oxidizing PTEN. The mechanism underlying this oxidation, occurring despite the presence of highly efficient and abundant cellular oxidant-protecting and reducing systems, continues to pose a perplexing conundrum. Here, we demonstrate that the presence of bicarbonate (HCO3-) promoted the rate of H2O2-mediated PTEN oxidation, probably through the formation of peroxymonocarbonate (HCO4-), consequently potentiated the phosphorylation of AKT. In essence, our findings consolidate the crucial role of HCO3- in the redox regulation of PTEN by H2O2, lead to the presumption regarding HCO4- as a signaling molecule during cellular physiological processes.
Medicine and Pharmacology, Medicine and Pharmacology
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