Interaction of bilirubin and biliverdin with reactive nitrogen species

FEBS Letters

Foresti, Roberta²  Kaur, Harparkash²  Green, Colin J.²  Motterlini, Roberto²  Naughton, Patrick²  Hughes, Martin N.¹ 

[1]Department of Chemistry, King's College London, London WC2R 2LS, UK

[2]Vascular Biology Unit, Department of Surgical Research, Northwick Park Institute for Medical Research, Watford Road, Y Block, Harrow, Middlesex HA1 3UJ, UK

关键词: Bilirubin;    Nitric oxide;    Nitroxyl;    Nitrosonium cation;    Antioxidant;    Nitrosative stress;    Anti-nitrosative capacity;    HO-1;    BV;    biliverdin IXα;    BR;    bilirubin IXα;    HO-1;    haem oxygenase-1;    NO;    nitric oxide;    NORS;    nitric oxide-related species;    ONOO−;    peroxynitrite;    NO+;    nitrosonium cation;    HNO;    nitroxyl;    SNAP;    S-nitroso-N-acetylpenicillamine;    GSNO;    S-nitrosoglutathione;    SNP;    sodium nitroprusside;    NAC;    N-acetylcysteine;    Cys;    cysteine;    Hcy;    homocysteine;    DEA-NO;    diethylamine NONOate;    AS;    sodium trioxodinitrate or Angeli's salt;    SIN-1;    3-morpholinosydnomine;    meso-BR;    meso-bilirubin IXα;    LTP;    linear tetrapyrrole;    HPLC;    high pressure liquid chromatography;   

DOI  :  10.1016/S0014-5793(03)00420-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Bilirubin (BR) and biliverdin (BV), two metabolites produced during haem degradation by haem oxygenase, possess strong antioxidant activities toward peroxyl radical, hydroxyl radical and hydrogen peroxide. Considering the importance attributed to nitric oxide (NO) and its congeners in the control of physiological and pathophysiological processes, we examined the interaction of BR and BV with NO and NO-related species in vitro. Exposure of BR and BV to agents that release NO or nitroxyl resulted in a concentration- and time-dependent loss of BR and BV, as assessed by high performance liquid chromatography. Peroxynitrite, a strong oxidant derived from the reaction of NO with superoxide anion, also showed high reactivity toward BR and BV. The extent of BR and BV consumption largely depended on the NO species being analysed and on the half-lives of the pharmacological compounds considered. Of major importance, BR and BV decomposition occurred also in the presence of pure NO under anaerobic conditions, confirming the ability of bile pigments to scavenge the gaseous free radical. Increasing concentrations of thiols prevented BR consumption by nitroxyl, indicating that bile pigments and thiol groups can compete and/or synergise the cellular defence against NO-related species. In view of the high inducibility of haem oxygenase-1 by NO-releasing agents in different cell types, the present findings highlight novel anti-nitrosative characteristics of BR and BV suggesting a potential function for bile pigments against the damaging effects of uncontrolled NO production.

【 授权许可】

Unknown