Abstract
This is a report on a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 2012 meeting in San Diego, California, on April 25, 2012. The symposium speakers summarized and critically evaluated our current understanding of the physiologic, pharmacological, and toxicological roles of NADPH–cytochrome P450 oxidoreductase (POR), a flavoprotein involved in electron transfer to microsomal cytochromes P450 (P450), cytochrome b5, squalene mono-oxygenase, and heme oxygenase. Considerable insight has been derived from the development and characterization of mouse models with conditional Por deletion in particular tissues or partial suppression of POR expression in all tissues. Additional mouse models with global or conditional hepatic deletion of cytochrome b5 are helping to clarify the P450 isoform- and substrate-specific influences of cytochrome b5 on P450 electron transfer and catalytic function. This symposium also considered studies using siRNA to suppress POR expression in a hepatoma cell–culture model to explore the basis of the hepatic lipidosis phenotype observed in mice with conditional deletion of Por in liver. The symposium concluded with a strong translational perspective, relating the basic science of human POR structure and function to the impacts of POR genetic variation on human drug and steroid metabolism.
Footnotes
This work was supported by the Canadian Institutes of Health Research [Grant MOP-93759]; the National Institutes of Health National Cancer Institute [Grant CA092596]; the National Institutes of Health National Institute of Environmental Health Sciences [Grants ES007462, ES018884]; the National Institutes of Health National Institute of General Medical Sciences [Grant GM082978]; the National Institutes of Health National Center for Complementary and Alternative Medicine [Grant AT005235]; Cancer Research UK [Programme Grant C4639/A5661]; and the Swiss National Science Foundation [Grants 3100A0-113719, 31003A-134926].
D.S.R., X.D., C.R.W., T.D.P., and A.V.P. contributed equally to this work.
- Received September 10, 2012.
- Accepted October 19, 2012.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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