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Cellular regulation by hydrogen peroxide
Sue Goo Rhee1, Tong-Shin Chang, Yun Soo Bae
1Laboratory of Cell Signaling, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. sgrhee@nih.gov
Journal of the American Society of Nephrology : JASN
|July 23, 2003
Summary
Hydrogen peroxide (H2O2) acts as a crucial signaling molecule in cells, produced upon receptor activation. Its targets include proteins with reactive cysteine residues, influencing cell signaling pathways.
Area of Science:
- Cellular signaling
- Biochemistry
- Molecular biology
Background:
- Hydrogen peroxide (H2O2) is increasingly recognized as a key intracellular signaling molecule.
- Its transient production is triggered by cell surface receptor activation, necessitating understanding its production, targets, and elimination.
- Growth factor-induced H2O2 production involves phosphatidylinositol 3-kinase (PtdIns 3-kinase).
Purpose of the Study:
- To elucidate the signaling pathway of H2O2 production upon receptor activation.
- To identify the molecular targets of H2O2.
- To understand the role of H2O2 in regulating protein tyrosine phosphorylation.
Main Methods:
- Investigated the role of PtdIns 3-kinase in H2O2 production.
- Examined the effect of H2O2 on protein tyrosine phosphatases (PTPs).
- Studied the involvement of peroxiredoxins in H2O2 elimination.
Main Results:
- PtdIns 3-kinase activation leads to the production of phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3), which recruits and activates Rac via a guanine nucleotide exchange factor, ultimately activating NADPH oxidase.
- H2O2 oxidizes the catalytic cysteine residue of PTPs, leading to their inactivation.
- Peroxiredoxins efficiently reduce intracellular H2O2 levels and appear to be regulated by protein phosphorylation.
Conclusions:
- Receptor tyrosine kinase activation alone may not suffice for increased protein tyrosine phosphorylation; concurrent H2O2-mediated PTP inhibition is likely required.
- H2O2 acts as a critical regulator of cellular signaling by modifying proteins, particularly through cysteine oxidation.
- Peroxiredoxins play a vital role in managing intracellular H2O2 levels, with their activity potentially modulated by phosphorylation.