2. Academic Validation
  3. Redox Regulation of Phosphatase and Tensin Homolog by Bicarbonate and Hydrogen Peroxide: Implication of Peroxymonocarbonate in Cell Signaling

Redox Regulation of Phosphatase and Tensin Homolog by Bicarbonate and Hydrogen Peroxide: Implication of Peroxymonocarbonate in Cell Signaling

  • Antioxidants (Basel). 2024 Apr 17;13(4):473. doi: 10.3390/antiox13040473.
Vu Hoang Trinh 1 2,  Jin-Myung Choi 3,  Thang Nguyen Huu 1,  Dhiraj Kumar Sah 1,  Hyun-Joong Yoon 1,  Sang-Chul Park 4,  Yu-Seok Jung 5,  Young-Keun Ahn 6,  Kun-Ho Lee 7 8,  Seung-Rock Lee 1
Affiliations

Affiliations

  • 1 Department of Biochemistry, Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 501190, Republic of Korea.
  • 2 Department of Oncology, Department of Medical Sciences, Pham Ngoc Thach University of Medicine, Ho Chi Minh City 700000, Vietnam.
  • 3 Luxanima Inc., Room 102, 12-55, Sandan-gil, Hwasun-eup, Hwasun-gun 58128, Republic of Korea.
  • 4 The Future Life & Society Research Center, Advanced Institute of Aging Science, Chonnam National University, Gwangju 61469, Republic of Korea.
  • 5 Chonnam National University Medical School, Gwangju 501190, Republic of Korea.
  • 6 Department of Cardiology, Chonnam National University Hospital, Gwangju 61469, Republic of Korea.
  • 7 Department of Biomedical Science, Chosun University, Gwangju 61452, Republic of Korea.
  • 8 Department of Neural Development and Disease, Korea Brain Research Institute, Daegu 41062, Republic of Korea.
PMID: 38671920 DOI: 10.3390/antiox13040473
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 contains 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 the stimulation of cell surface receptors, the activity of NADPH Oxidase (NOX) 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-), and consequently potentiated the phosphorylation of Akt. Acetazolamide (ATZ), a Carbonic Anhydrase (CA) inhibitor, was shown to diminish the oxidation of PTEN. Thus, CA can also be considered as a modulator in this context. In essence, our findings consolidate the crucial role of HCO3- in the redox regulation of PTEN by H2O2, leading to the presumption that HCO4- is a signaling molecule during cellular physiological processes.

Keywords

H2O2; PTEN redox regulation; bicarbonate; carbonic anhydrase; cell signaling; peroxymonocarbonate.

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