Homocysteine transport by human aortic endothelial cells: Identification and properties of import systems

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• 作者：Beatrix Bü ; dy ; RoseMarie O’ ; Neill ; Patricia M. DiBello ; Shantanu Sengupta and Donald W. Jacobsen
• 关键词：Homocysteine ; Homocystine ; Hyperhomocysteinemia ; Homocystinuria ; Homocysteine import ; Cysteine transport systems ; Endothelial cells ; Endothelium ; Cardiovascular disease
• 刊名：Archives of Biochemistry and Biophysics
• 出版年：2006
• 出版时间：15 February 2006
• 年：2006
• 卷：446
• 期：2
• 页码：119-130
• 全文大小：709 K

文摘

Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Transport of l-homocysteine into and out of the human vascular endothelium is poorly understood. We hypothesized that cultured human aortic endothelial cells (HAEC) would import l-homocysteine on one or more of the l-cysteine transport systems. Inhibitors of the transporters were used to characterize the uptake of [³⁵S]l-homocysteine, [³⁵S]l-homocystine, and [³⁵S]l-cysteine. We found that l-homocysteine uptake is mediated by the sodium-dependent cysteine transport systems X_AG, ASC, and A, and the sodium-independent transport system L. Thus, HAEC utilize multiple cysteine transporters (X_AG L > ASC > A) to import l-homocysteine. Kinetic analysis supported the uptake results. Michaelis–Menten constants (K_m) for the four systems yielded values of 19.0, 27.1, 112, and 1000 μM for systems L, X_AG, ASC, and A, respectively. The binding and uptake of [³⁵S]l-homocystine, the disulfide homodimer of l-homocysteine, was mediated by systems X_AG, L, and ASC but not by system A. In contrast to [³⁵S]l-homocysteine, system x_c was active for [³⁵S]l-homocystine uptake. A similar pattern was observed for [³⁵S]l-cysteine. Thus, l-homocysteine and l-homocystine found in hyperhomocysteinemic subjects can gain entry into the vascular endothelium by way of multiple l-cysteine transporters.