UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Cytochrome P450 oxidoreductase participates in nitric oxide consumption by rat brain

Hall, C.N.; Keynes, R.G.; Garthwaite, J.; (2009) Cytochrome P450 oxidoreductase participates in nitric oxide consumption by rat brain. Biochemical Journal , 419 (2) pp. 411-418. 10.1042/BJ20082419. Green open access

[thumbnail of 20120.pdf]
Preview
PDF
20120.pdf

Download (429kB)

Abstract

In low nanomolar concentrations, NO (nitric oxide) functions as a transmitter in brain and other tissues, whereas near-micromolar NO concentrations are associated with toxicity and cell death. Control of the NO concentration, therefore, is critical for proper brain function, but, although its synthesis pathway is well-characterized, the major route of breakdown of NO in brain is unclear. Previous observations indicate that brain cells actively consume NO at a high rate. The mechanism of this consumption was pursued in the present study. NO consumption by a preparation of central glial cells was abolished by cell lysis and recovered by addition of NADPH. NADPH-dependent consumption of NO localized to cell membranes and was inhibited by proteinase K, indicating the involvement of a membrane-bound protein. Purification of this activity yielded CYPOR (cytochrome P450 oxidoreductase). Antibodies against CYPOR inhibited NO consumption by brain membranes and the amount of CYPOR in several cell types correlated with their rate of NO consumption. NO was also consumed by purified CYPOR but this activity was found to depend on the presence of the vitamin E analogue Trolox (6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid), included in the buffer as a precaution against inadvertent NO consumption by lipid peroxidation. In contrast, NO consumption by brain membranes was independent of Trolox. Hence, it appears that, during the purification process, CYPOR becomes separated from a partner needed for NO consumption. Cytochrome P450 inhibitors inhibited NO consumption by brain membranes, making these proteins likely candidates.

Type: Article
Title: Cytochrome P450 oxidoreductase participates in nitric oxide consumption by rat brain
Open access status: An open access version is available from UCL Discovery
DOI: 10.1042/BJ20082419
Publisher version: http://dx.doi.org/10.1042/BJ20082419
Language: English
Additional information: © 2009 The Author(s) The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Brain, cytochrome P450 oxidoreductase (CYPOR), NADPH, nitric oxide
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/20120
Downloads since deposit
213Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item