Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 41, Issue 1, Pages 86-91Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2006.03.010
Keywords
protein tyrosine phosphatase 1B; hydrogen peroxide; glutathione; glutathione disulfide
Funding
- NHLBI NIH HHS [R01 HL037556-17, R01 HL037556, HL37556] Funding Source: Medline
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H2O2 produced by stimulation of the macrophage NADPH oxidase is involved both in bacterial killing and as a second messenger in these cells. Protein tyrosine phosphatases (PTPs) are targets for H2O2 signaling through oxidation of their catalytic cysteine, resulting in inhibition of their activity. Here, we show that, in the rat alveolar macrophage NR8383 cell line, H2O2 produced through the ADP-stimulated respiratory burst induces the formation of a disulfide bond between PTP1B and GSH that was detectable with an antibody to glutathione-protein complexes and was reversed by DTT addition. PTP1B glutathionylation was dependent on H2O2 as the presence of catalase at the time of ADP stimulation inhibited the formation of the conjugate. Interestingly, other PTPs, i.e., SHP-1 and SHP-2, did not undergo glutathionylation in response to ADP stimulation of the respiratory burst, although glutathionylation of these proteins could be shown by reaction with 25 mM glutathione disulfide in vitro. While previous studies have suggested the reversible oxidation of PTP1B during signaling or showed PTP1B glutathionylation in vitro, the present study directly demonstrates that physiological stimulation of H2O2 production results in PTP1B glutathionylation in intact cells, which may affect downstream signaling. (c) 2006 Elsevier Inc. All rights reserved.
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