Characterization of 5-oxo-L-prolinase in normal and tumor tissues of humans and rats: a potential new target for biochemical modulation of glutathione.

摘要: 5-Oxo-L-prolinase (5-OPase) is an enzyme of the gamma-glutamyl cycle involved in synthesis and metabolism glutathione (GSH), which known to protect cells from cytotoxic effects chemotherapy radiation. Previous studies on rats have shown that administration cysteine prodrug L-2-oxothiazolidine-4-carboxylate, a 5-oxo-L-proline analogue metabolized by 5-OPase, preferentially increases GSH content normal tissues while paradoxically decreasing it tumor results enhanced vivo response anticancer drug melphalan. These observations initiated present study 5-OPase experimental models clinical specimens investigate potential role this selective modulation tissues. First, activity was measured tumor-bearing rats, peripheral mononuclear human subjects, surgically resected adjacent patients. We found kidney, liver, lung significantly lower than rats. Second, we raised polyclonal IgG anti-5-OPase antibody immunizing rabbits with purified rat kidney. This has very high affinity (shown immunoprecipitation) specificity Western blot) cross-reacts blot immunohistochemistry). It then used examine distribution paired neoplastic using immunohistochemistry. Examination stomach revealed level In colon tissues, there no significant difference between findings could implications for both carcinogenesis therapy.