Dall'Asta V, Bussolati O, Sala R, Rotoli B M, Sebastio G, Sperandeo M P, Andria G, Gazzola G C
Dipartimento di Medicina Sperimentale, Sezione di Patologia Generale e Clinica, Plesso Biotecnologico Integrato, Università degli Studi di Parma, 43100 Parma, Italy.
Am J Physiol Cell Physiol. 2000 Dec;279(6):C1829-37. doi: 10.1152/ajpcell.2000.279.6.C1829.
In lysinuric protein intolerance (LPI), impaired transport of cationic amino acids in kidney and intestine is due to mutations of the SLC7A7 gene. To assess the functional consequences of the LPI defect in nonepithelial cells, we have characterized cationic amino acid (CAA) transport in human fibroblasts obtained from LPI patients and a normal subject. In both cell types the bidirectional fluxes of arginine are due to the additive contributions of two Na(+)-independent, transstimulated transport systems. One of these mechanisms, inhibited by N-ethylmaleimide (NEM) and sensitive to the membrane potential, is identifiable with system y(+). The NEM- and potential-insensitive component, suppressed by L-leucine only in the presence of Na(+), is mostly due to the activity of system y(+)L. The inward and outward activities of the two systems are comparable in control and LPI fibroblasts. Both cell types express SLC7A1 (CAT1) and SLC7A2 (CAT2B and CAT2A) as well as SLC7A6 (y+LAT2) and SLC7A7 (y+LAT1). We conclude that LPI fibroblasts exhibit normal CAA transport through system y(+)L, probably referable to the activity of SLC7A6/y+LAT2.
在赖氨酸尿性蛋白不耐受症（LPI）中，肾脏和肠道中阳离子氨基酸转运受损是由SLC7A7基因突变所致。为了评估LPI缺陷在非上皮细胞中的功能后果，我们对从LPI患者和一名正常受试者获取的人成纤维细胞中的阳离子氨基酸（CAA）转运进行了表征。在这两种细胞类型中，精氨酸的双向通量是由两个不依赖Na⁺、经转刺激的转运系统的累加作用所致。其中一种机制受N - 乙基马来酰亚胺（NEM）抑制且对膜电位敏感，可确定为y⁺系统。仅在存在Na⁺的情况下受L - 亮氨酸抑制的NEM和电位不敏感成分，主要归因于y⁺L系统的活性。在对照和成纤维细胞中，这两个系统的内向和外向活性相当。两种细胞类型均表达SLC7A1（CAT1）、SLC7A2（CAT2B和CAT2A）以及SLC7A6（y⁺LAT2）和SLC7A7（y⁺LAT1）。我们得出结论，LPI成纤维细胞通过y⁺L系统表现出正常的CAA转运，这可能归因于SLC7A6/y⁺LAT2的活性。
