Iron attenuates nitric oxide level and iNOS expression in endotoxin‐treated mice

FEBS Letters

Mak, I.Tong²  Weglicki, William B²  Mattson, David L¹  Komarov, Andrei M² 

[1] Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA;Division of Experimental Medicine, The George Washington University Medical Center, 2300 Eye Street, NW, Ross Hall, Rm. 451A, Washington, DC 20037, USA

关键词: Septic shock;    Nitric oxide;    Iron;    Inducible nitric oxide synthase;    Nitrosyl iron complex;    Spin trapping;    EPR;    electron paramagnetic resonance;    LPS;    lipopolysaccharide;    iNOS;    inducible nitric oxide synthase;    ROS;    reactive oxygen species;    MGD;    N-methyl-d-glucamine dithiocarbamate;    DETC;    diethyldithiocarbamate;    SIN-1;    3-morpholinosydnonimine;    HbNO;    nitrosyl hemoglobin;    HRP;    horseradish peroxidase;   

DOI  :  10.1016/S0014-5793(98)00181-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The effect of exogenous Fe-citrate complex (Fe doses of 120 and 240 μmol/kg) on nitric oxide (NO) production in vivo has been studied in blood and liver tissue of endotoxin-treated mice. Fe-citrate complex was administered to mice subcutaneously at the same time with intravenous injection of Escherichia coli lipopolysaccharide (LPS). Iron-dependent decrease in NO⁻ ₂/NO⁻ ₃ and nitrosyl hemoglobin levels in blood of animals was detected at 6 h after LPS administration, suggesting systemic attenuation of NO generation. NO production in the liver tissue of LPS-treated mice was decreased after Fe administration judging from the amount of mononitrosyl-iron complexes formed in the tissue by diethyldithiocarbamate. The iNOS protein determination in the liver tissue of LPS-treated mice demonstrated iron-dependent inhibition of iNOS expression. We have found previously that exogenous iron does not affect systemic NO level when it is given at 6 h after LPS injection, i.e. after iNOS expression. This is a first report demonstrating iron-dependent iNOS down-regulation in endotoxin-treated mice.

【 授权许可】

Unknown