Oxidized protein hydrolase

Carnosine can affect gene expression. Ikeda et al. (1999) showed that carnosine markedly upregulates vimentin synthesis in cultured rat fibroblasts, while an association between carnosine and vimentin, a cytoskele-tal, intermediate filament protein has been noted in glial cells and neurons (Bonfanti et al., 1999). Interestingly, it has also been shown that the protease, oxidized protein hydrolase (OPH), is coexpressed with vimentin in COS cells (Shimizu et al., 2004). Thus, it is at least possible that carnosine could induce synthesis of OPH in the cultured human fibroblasts and thereby increase the cellular ability to eliminate oxidized... 

Shimizu, K., Kiuchi, Y., Ando, K., Hayakawa, M., and Kikugawa, K. (2004). Coordination of oxidized protein hydrolase and the proteasome in the clearance of cytotoxic denatured proteins. Biochem. Biophys. Acta 324,140-146. 

Fujino, T., Wataiiabe, K Beppu, M., Kikugawa, K., and Yasiida. H. (2000). Identification of oxidized protein hydrolase of human erythrocytes as aeylpeptide hydrolase. Biochim. Biophy.s. Ada 1478. 102-112. 

Castegna et al, 2003 Sultana et al, 2006b). Ubiquitin carboxyl-terminal hydrolase L-1 (UCH L-1), one of the components of the proteosomal pathway, was identified as an oxidized protein in the inferior parietal and hippocampal regions of AD, further suggesting a role for nitration in protein accumulation (Castegna et al., 2003 Sultana et al., 2006b). 

Figure 7.22 Metabolism of bromobenzene. The bromobenzene 2,3-oxide and 3,4-oxide may undergo chemical rearrangement to the 2- and 4-bromophenol, respectively. Bromobenzene 3,4-oxide may also be conjugated with glutathione, and in its absence react with tissue proteins. An alternative detoxication pathway is hydration to the 3,4-dihydrodiol via epoxide hydrolase.

It has been proposed that metabolic activation of diphenylhydantoin may be responsible for the teratogenicity. After the administration of radioactively labeled diphenylhydantoin to pregnant mice, radioactive drug or a metabolite was found to be covalently bound to protein in the embryo. It was shown that both the teratogenicity and embryolethality of diphenylhydantoin could be increased by using an inhibitor of epoxide hydrolase (see chap. 4), trichloropropene oxide. Similarly, the covalent binding of radiolabeled diphenylhydantoin to protein was also increased by this treatment. 

The metabolite of bromobenzene that is believed to be responsible for the hepatic necrosis is bromobenzene 3,4-oxide. This reacts with liver cell protein, which causes cell death. The reactive metabolite can be detoxified by conjugation with glutathione or be detoxified by metabolism to a dihydrodiol by epoxide hydrolase. Pretreatment of animals with the enzyme inducer 3-methylcholanthrene decreases the toxicity. This is because it increases metabolism to the 2,3-oxide. This reactive metabolite is not as toxic as the 3,4-bromobenzene oxide readily undergoing rearrangement to 2-bromophenol. 3-Methylcholanthrene also induces epoxide hydrolase and so increases detoxication. 

W. M., Booze, R., Markesbery, W. R., Butterfield, D. A. Proteomic identification of oxidatively modified proteins in Alzheimer s disease brain. Part I creatine kinase BB, glutamine synthase, and ubiq-uitin carboxy-terminal hydrolase L-l. Free Radical Biol. Med. 2002, 33 562-571. 

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