Protein Information

ID 29
Name NADPH cytochrome P450 reductase
Synonyms CPR; CYPOR; Cytochrome P 450 reductase; Cytochrome P450 reductase; NADPH cytochrome P450 reductase; NADPH cytochrome P450 reductase; P450 (cytochrome) oxidoreductase; P450R…

Compound Information

ID 1084
Name paraquat
CAS 1,1′-dimethyl-4,4′-bipyridinium

Reference

PubMed Abstract RScore(About this table)
16495354 Han JF, Wang SL, He XY, Liu CY, Hong JY: Effect of genetic variation on human cytochrome p450 reductase-mediated paraquat cytotoxicity. Toxicol Sci. 2006 May;91(1):42-8. Epub 2006 Feb 22.
Paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride) is a widely used herbicide and is highly toxic to human and animals. The mechanisms of paraquat toxicity involve the generation of superoxide anion through the process of redox cycling. NADPH-cytochrome P450 oxidoreductase (POR) has been reported to be a major enzyme for one-electron reduction of paraquat that initiates the redox cycling. Recently, a total of six missense variants of human POR have been identified in patients with discorded steroidogenesis. However, the effect of these genetic variations on POR-mediated paraquat toxicity is not known. Using the Flp-In Chinese hamster ovary (CHO) cells stably expressing either mouse or human POR and the cells with POR knockdown by siRNA, we confirmed that POR is responsible for paraquat-induced cytotoxicity. We further used this validated system to compare paraquat-induced toxicity among the cells that stably expressed wild-type human POR and its natural variants. While there was no difference in paraquat-induced toxicity between the cells expressing wild-type human POR and the Cys569Tyr variant, the toxicity in cells expressing all the other variants (Tyr181Asp, Ala287Pro, Arg457His, Val492Glu, and Val608Phe) was significantly decreased. Our results provide further evidence on the important role of POR in paraquat-induced toxicity and suggest that individuals carrying the functional variant POR alleles may have an altered susceptibility to paraquat exposure.
81(1,1,1,1)