Protein S-thiolation in hepatocytes stimulated by t-butyl hydroperoxide, menadione, and neutrophils.

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Chai YC, Hendrich S, Thomas JA

Protein S-thiolation in hepatocytes stimulated by t-butyl hydroperoxide, menadione, and neutrophils.

Arch Biochem Biophys. 1994 Apr;310(1):264-72.

PubMed ID

8161215 [ View in PubMed

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Abstract

In order to examine potentially important S-thiolated proteins, 35S-labeled hepatocytes were exposed to oxidative stress. A similar group of S-thiolated proteins including carbonic anhydrase III was observed in cells treated with t-butyl hydroperoxide, menadione, or stimulated neutrophils. The radioactive thiols bound to hepatocyte proteins were identified by HPLC and more than 85% was glutathione. In menadione-treated hepatocytes, proteins were gradually S-thiolated over 30 min and 25% of the cellular glutathione pool became protein-bound. In t-butyl hydroperoxide-treated cells, S-thiolation was more transient and 11% of the glutathione was protein-bound. Neutrophil-treated hepatocytes had nearly the same amount of protein S-thiolation (8% after 25 min). Two major proteins that were S-thiolated in untreated hepatocytes did not increase during any form of oxidative stress. In neutrophil-treated hepatocytes protein S-thiolation was not accompanied by either formation of glutathione disulfide or a measurable change in the total amount of glutathione. In both t-butyl hydroperoxide-and menadione-treated cells there was extensive formation of glutathione disulfide and in menadione-treated cells a significant increase in the total hepatocyte glutathione pool was observed. This result suggests that protein S-thiolation may occur by mechanisms that do not result from thiol/disulfide exchange between glutathione disulfide and protein sulfhydryls. It is suggested that a thiyl radical intermediate is important in neutrophil-mediated protein S-thiolation.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Menadione	Vitamin K-dependent protein S	Protein	Humans	Unknown	Activator	Details