• Users Online: 96
  • Home
  • Print this page
  • Email this page
RESEARCH ARTICLE
Year : 2017  |  Volume : 7  |  Issue : 1  |  Page : 37-44

Drug-enhanced carbon monoxide production from heme by cytochrome P450 reductase


Department of Biomedical & Molecular Sciences, Queen's University, Kingston, Ontario, Canada

Correspondence Address:
Kanji Nakatsu
Department of Biomedical & Molecular Sciences, Queen's University, Kingston, Ontario
Canada
Login to access the Email id

Source of Support: This study was funded by the Canadian Institutes of Health Research grant MOP 119467., Conflict of Interest: None


DOI: 10.4103/2045-9912.202908

Rights and Permissions

Carbon monoxide (CO) formed endogenously is considered to be cytoprotective, and the vast majority of CO formation is attributed to the degradation of heme by heme oxygenases-1 and -2 (HO-1, HO-2). Previously, we observed that brain microsomes containing HO-2 produced many-fold more CO in the presence of menadione and its congeners; herein we explored these observations further. We determined the effects of various drugs on CO production of rat brain microsomes and recombinant human cytochrome P450 reductase (CPR); CO was measured by gas chromatography with reductive detection. Brain microsomes of Sprague-Dawley rats or recombinant human cytochrome P450 reductase (CPR) were incubated with NADPH and various drugs in closed vials in phosphate buffer at pH 7.4 and 37°C. After 15 minutes, the reaction was stopped by cooling in dry ice, and the headspace gas was analyzed for CO production using gas chromatography with reductive (mercuric oxide) detection. We observed drug-enhanced CO production in the presence of both microsomes and recombinant CPR alone; the presence of HO was not required. A range of structurally diverse drugs were capable of amplifying this CO formation; these molecules had structures consistent with redox cycling capability. The addition of catalase to a reaction mixture, that contained activating drugs, inhibited the production of CO. Drug-enhanced CO formation can be catalyzed by CPR. The mechanism of CPR activation was not through classical drug-receptor mediation. Redox cycling may be involved in the drug-induced amplification of CO production by CPR through the production of reactive oxygen species.


[FULL TEXT] [PDF]*
Print this article     Email this article
 Next article
 Previous article
 Table of Contents

 Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
 Citation Manager
 Access Statistics
 Reader Comments
 Email Alert *
 Add to My List *
 * Requires registration (Free)
 

 Article Access Statistics
    Viewed162    
    Printed7    
    Emailed0    
    PDF Downloaded65    
    Comments [Add]    

Recommend this journal