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人多形核白细胞中 4-羟基-2-壬烯醛的代谢。

Metabolism of 4-hydroxy-2-nonenal in human polymorphonuclear leukocytes.

机构信息

Department of Physiotherapy and Gerontology, KortexMed Institute of Medical Education, Bad Harzburg, Germany.

出版信息

Arch Biochem Biophys. 2010 Nov 15;503(2):248-52. doi: 10.1016/j.abb.2010.08.018. Epub 2010 Sep 4.

DOI:10.1016/j.abb.2010.08.018
PMID:20804722
Abstract

Intracellular metabolism of 4-hydroxy-2-nonenal (HNE), a major product and mediator of oxidative stress and inflammation, is analyzed in resting and fMLP-stimulated human polymorphonuclear leukocytes (PMNL), where this compound is generated during activation of the respiratory burst. HNE consumption rate in PMNL is very low, if compared to other cell types (rat hepatocytes, rabbit fibroblasts), where HNE metabolism is always an important part of secondary antioxidative defense mechanisms. More than 98% of HNE metabolites are identified. The pattern of HNE intermediates is quite similar in stimulated and resting PMNL - except for higher water formation in resting PMNL - while the initial velocity of HNE degradation is somewhat higher in resting cells, 0.44 instead of 0.28 nmol/(min×10(6) cells). The main products of HNE metabolism are 4-hydroxynonenoic acid (HNA), 1,4-dihydroxynonene (DHN) and the glutathione adducts with HNE, HNA, and DHN. Protein-bound HNE and water account for about 3-4% of the total HNE derivatives in stimulated cells, while in resting cells protein-bound HNE and water are 4% and 20%, respectively. Cysteinyl-glycine-HNE adduct and mercapturic acids contribute to about 5%.

摘要

细胞内代谢 4-羟基-2-壬烯醛 (HNE),一种氧化应激和炎症的主要产物和介质,在静止和 fMLP 刺激的人多形核白细胞 (PMNL) 中进行分析,在该化合物在呼吸爆发激活期间产生。与其他细胞类型(大鼠肝细胞、兔成纤维细胞)相比,PMNL 中的 HNE 消耗率非常低,在这些细胞中,HNE 代谢始终是次级抗氧化防御机制的重要组成部分。鉴定出超过 98%的 HNE 代谢物。刺激和静止 PMNL 中的 HNE 中间体模式非常相似-除了静止 PMNL 中形成更多的水-而静止细胞中 HNE 降解的初始速度略高,为 0.44 而不是 0.28 nmol/(min×10(6) 细胞)。HNE 代谢的主要产物是 4-羟基壬烯酸 (HNA)、1,4-二羟基壬烯 (DHN) 以及与 HNE、HNA 和 DHN 的谷胱甘肽加合物。刺激细胞中总 HNE 衍生物的约 3-4%为结合蛋白的 HNE 和水,而在静止细胞中,结合蛋白的 HNE 和水分别为 4%和 20%。半胱氨酸甘氨酸-HNE 加合物和硫尿酸盐约占 5%。

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