Haem oxygenase-1 (HO-1) is a highly inducible stress protein that removes haem from cells with the release of biliverdin, carbon monoxide and low-molecular-mass iron (LMrFe). Several antioxidant functions have been ascribed to HO; its induction is considered to be a protective event. However, LMrFe produced during haem catabolism might elicit a pro-oxidant response, with deleterious consequences. We therefore investigated the delicate balance between pro-oxidant and antioxidant events with the use of a microsomal lipid peroxidation (LPO) system. By using microsomal-bound HO in an NADPH-dependent LPO system, we assessed the pro-oxidant nature of the released LMrFe and the antioxidant effect of the released bilirubin. Hb, a biologically relevant substrate for HO, was included with the microsomes to supplement the source of haem iron and to promote LPO. We found significant increases in microsomal LPO, by using the thiobarbituric acid (TBA) test, after incubation with Hb. This Hb-stimulated peroxidation was inhibited by HO inhibitors and by iron chelators, suggesting a HO-driven, iron-dependent mechanism. GLC-MS was employed to measure the specific LPO product 4-hydroxy-2-nonenal and to confirm our TBA test results. A HO inhibitor attenuated an increase in intracellular LMrFe that occurred after treatment of rat pulmonary artery smooth-muscle cells with Hb. Additionally, exogenously added bilirubin at an equimolar concentration to the LMrFe present in both microsomal and liposomal systems was unable to prevent the pro-oxidant effect of the iron. Under certain circumstances HO can act as a pro-oxidant and seems to have a role in stimulating microsomal LPO.
Skip Nav Destination
Article navigation
November 1999
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Research Article|
November 08 1999
Haem oxygenase shows pro-oxidant activity in microsomal and cellular systems: implications for the release of low-molecular-mass iron
Nicholas J. LAMB;
Nicholas J. LAMB
1Oxygen Chemistry Laboratory, Directorate of Anaesthesia and Critical Care, Royal Brompton and Harefield NHS Trust, Sydney Street, London SW3 6NP, U.K.
Search for other works by this author on:
Gregory J. QUINLAN;
Gregory J. QUINLAN
1Oxygen Chemistry Laboratory, Directorate of Anaesthesia and Critical Care, Royal Brompton and Harefield NHS Trust, Sydney Street, London SW3 6NP, U.K.
Search for other works by this author on:
Sharon MUMBY;
Sharon MUMBY
1Oxygen Chemistry Laboratory, Directorate of Anaesthesia and Critical Care, Royal Brompton and Harefield NHS Trust, Sydney Street, London SW3 6NP, U.K.
Search for other works by this author on:
Timothy W. EVANS;
Timothy W. EVANS
1Oxygen Chemistry Laboratory, Directorate of Anaesthesia and Critical Care, Royal Brompton and Harefield NHS Trust, Sydney Street, London SW3 6NP, U.K.
Search for other works by this author on:
John M. C. GUTTERIDGE
John M. C. GUTTERIDGE
1
1Oxygen Chemistry Laboratory, Directorate of Anaesthesia and Critical Care, Royal Brompton and Harefield NHS Trust, Sydney Street, London SW3 6NP, U.K.
1To whom correspondence should be addressed (e-mail jmcg@rbh.nthames.nhs.uk).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
March 08 1999
Revision Received:
September 03 1999
Accepted:
September 20 1999
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1999
1999
Biochem J (1999) 344 (1): 153–158.
Article history
Received:
March 08 1999
Revision Received:
September 03 1999
Accepted:
September 20 1999
Citation
Nicholas J. LAMB, Gregory J. QUINLAN, Sharon MUMBY, Timothy W. EVANS, John M. C. GUTTERIDGE; Haem oxygenase shows pro-oxidant activity in microsomal and cellular systems: implications for the release of low-molecular-mass iron. Biochem J 15 November 1999; 344 (1): 153–158. doi: https://doi.org/10.1042/bj3440153
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.