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Iron stimulation of chemiluminescence by microsomes and purified NADPH-cytochrome P-450 reductase

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:6279686

Low level chemiluminescence (CL) was measured as an assay of the steady state level of production of oxygen radicals during microsomal electron transfer. In the presence of an NADPH-generating system, antioxidant-sensitive CL was observed with isolated rat liver microsomes. Depending on the nature of the chelating agent, ferric iron markedly affected this CL. For example, ferric-EDTA inhibited, whereas ferric-ADP stimulated CL. This response to iron chelators was identical to that found when measuring microsomal lipid peroxidation, but was opposite to the catalytic effectiveness of ferric-chelates in stimulating microsomal generation of hydroxyl radicals. Similar studies were conducted with purified NADPH-cytochrome P-450 reductase in the presence of t-butyl hydroperoxide (t-BOOH). No CL was observed in the absence of added iron. The addition of ferric-EDTA or ferric-detapac stimulated production of CL, whereas ferric chloride or ferric-ATP has little or no effect. This pattern of response to iron chelates is opposite to that found with the microsomes. CL was inhibited by catalase and OH scavengers such as ethanol and DMSO but not by superoxide dismutase. Thus, CL by the reductase system appears to involve the generation of OH via a Fenton-type of reaction, and subsequent interaction of OH with t-BOOH to produce excited species.

Research Organization:
Mount Sinai School of Medicine, New York, NY
OSTI ID:
6279686
Report Number(s):
CONF-870644-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 46:6; ISSN FEPRA
Country of Publication:
United States
Language:
English