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Intracellular metabolism of 4-hydroxynonenal.
Molecular Aspects of Medicine ( IF 8.7 ) Pub Date : 2003-08-02 , DOI: 10.1016/s0098-2997(03)00011-6
Werner Siems 1 , Tilman Grune
Affiliation  

4-hydroxynonenal (HNE) is a major aldehydic product of lipid peroxidation known to exert a multitude of biological, cytotoxic, and signal effects. Mammalian cells possess highly active pathways of HNE metabolism. The metabolic fate of HNE was investigated in various mammalian cells and organs such as hepatocytes, intestinal enterocytes, renal tubular cells, aortic and brain endothelial cells, synovial fibroblasts, neutrophils, thymocytes, heart, and tumor cells. The experiments were carried out at 37 degrees C at initial HNE concentrations between 1 microM--that means in the range of physiological and pathophysiologically relevant HNE levels--to 100 microM. In all cell types which were investigated, 90-95% of 100 microM HNE were degraded within 3 min of incubation. At 1 microM HNE the physiological blood serum level of about 0.1-0.2 microM was restored already after 10-30 s. As primary products of HNE in hepatocytes and other cell types the glutathione-HNE-1:1-conjugate, the hydroxynonenoic acid and the corresponding alcohol of HNE, the 1,4-dihydroxynonene, were identified. Furthermore, the beta-oxidation of hydroxynonenoic acid including the formation of water was demonstrated. The quantitative share of HNE binding to proteins was low with about 2-8% of total HNE consumption. The glycine-cysteine-HNE, cysteine-HNE adducts and the mercapturic acid from glutathione-HNE adduct were not formed in the most cell types, but in kidney cells and neutrophils. The rapid metabolism underlines the role of HNE degrading pathways in mammalian cells as important part of the secondary antioxidative defense mechanisms in order to protect proteins from modification by aldehydic lipid peroxidation products.

中文翻译:

4-羟基壬烯醛的细胞内代谢。

4-羟基壬烯醛(HNE)是脂质过氧化作用的主要醛类产物,已知会产生多种生物学,细胞毒性和信号作用。哺乳动物细胞具有高度活跃的HNE代谢途径。在各种哺乳动物细胞和器官(例如肝细胞,肠肠上皮细胞,肾小管细胞,主动脉和脑内皮细胞,滑膜成纤维细胞,中性粒细胞,胸腺细胞,心脏和肿瘤细胞)中研究了HNE的代谢命运。实验是在37摄氏度,初始HNE浓度在1 microM(即生理和病理生理相关的HNE水平范围)至100 microM之间进行的。在研究的所有细胞类型中,100 microM HNE的90-95%在孵育3分钟内降解。在1 microM HNE下,生理血清水平约为0.1-0。10-30 s后已经恢复了2 microM。作为肝细胞和其他细胞类型中HNE的主要产物,已鉴定出谷胱甘肽-HNE-1:1-缀合物,羟基壬烯酸和HNE的相应醇1,4-二羟基壬烯。此外,证明了羟基壬烯酸的β-氧化包括水的形成。HNE与蛋白质结合的定量份额很低,约占总HNE消耗量的2-8%。谷胱甘肽-HNE加合物中的甘氨酸-半胱氨酸-HNE加合物,半胱氨酸-HNE加合物和巯基酸不是在大多数细胞类型中形成的,而是在肾细胞和中性粒细胞中形成的。
更新日期:2019-11-01
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