巨噬细胞合成的蝶呤7,8-二氢新蝶呤对THP-1细胞介导的低密度脂蛋白氧化的抑制作用

Inhibition of THP-1 cell-mediated low-density lipoprotein oxidation by the macrophage-synthesised pterin, 7,8-dihydroneopterin.

作者信息

Gieseg Steven P, Cato Sara

机构信息

Free Radical Biochemistry Laboratory, Department of Zoology, University of Canterbury, Christchurch, New Zealand.

出版信息

Redox Rep. 2003;8(2):113-5. doi: 10.1179/135100003125001396.

DOI:10.1179/135100003125001396

PMID:12804014

Abstract

Human macrophages release the pterin, 7,8-dihydroneopterin when exposed to the immune stimulant gamma-interferon (IFN-gamma). Previous in vitro studies have shown 7,8-dihydroneopterin is a potent antioxidant, which inhibits copper- and peroxyl-radical mediated low-density lipoprotein (LDL) oxidation. Using THP-1 cells, a human derived monocyte-like cell line, we have found that low micromolar concentrations of 7,8-dihydroneopterin inhibit cell mediated oxidation of LDL, as measured by electrophoretic mobility, alpha-tocopherol loss, and lipid oxidation. Stimulation of the THP-1 cells with IFN-gamma caused a significant reduction in the cells' ability to oxidise LDL. The extracellular pterin concentration increased from 0 to 16 nM with IFN-gamma stimulation, while the intracellular concentration increased from 0.21 to 1.69 nmol/mg cell protein.

摘要

人类巨噬细胞在暴露于免疫刺激剂γ-干扰素（IFN-γ）时会释放蝶呤——7,8-二氢新蝶呤。先前的体外研究表明，7,8-二氢新蝶呤是一种有效的抗氧化剂，可抑制铜和过氧自由基介导的低密度脂蛋白（LDL）氧化。使用THP-1细胞（一种源自人类的单核细胞样细胞系），我们发现低微摩尔浓度的7,8-二氢新蝶呤可抑制细胞介导的LDL氧化，这通过电泳迁移率、α-生育酚损失和脂质氧化来衡量。用IFN-γ刺激THP-1细胞会导致细胞氧化LDL的能力显著降低。随着IFN-γ刺激，细胞外蝶呤浓度从0增加到16 nM，而细胞内浓度从0.21增加到1.69 nmol/mg细胞蛋白。