Wu Yihao, Yin Qiqi, Lin Su, Huang Xiaoyan, Xia Quan, Chen Zhe, Zhang Xingwei, Yang Deye
Division of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Department of Internal Medicine, The Third People's Hospital at Anji, Huzhou, Zhejiang 313301, P.R. China.
Mol Med Rep. 2017 Jul;16(1):887-893. doi: 10.3892/mmr.2017.6620. Epub 2017 May 25.
The kidney serves a central role in the control of blood pressure through the release of vasoactive substances and the urinary excretion of Na+. Patients with essential hypertension usually exhibit persistent high blood pressure accompanied by Na+ retention. L-dihydroxyphenylalanine (L‑DOPA) is an amino acid, converted by the enzyme aromatic L‑amino acid decarboxylase to dopamine. The uptake of L‑DOPA by cells of the proximal tubular epithelium of the kidney is controlled by the L‑type amino acid transporter 2 (LAT2). LAT2 belongs to the solute carrier family 7 (SLC7) of amino acid transporters and is coded by the SLC7A8 gene. SLC7A8 expression is increased in the second‑order mesenteric arteries and kidneys of spontaneously hypertensive rats. The present study aimed to investigate the physiological role of the SLC7A8 gene in L‑DOPA handling by kidney cells. Selective upregulation of SLC7A8 mRNA and protein levels was achieved by adenoviral transduction of NRK‑52E cells, which retain several properties of proximal tubular epithelial cells. In addition, L‑DOPA uptake was determined using high performance liquid chromatography; NRK‑52E cells expressing SLC7A8 exhibited increased uptake of L‑DOPA. The results of the present study suggested that SLC7A8 may serve a critical role in blood pressure control through regulating L‑DOPA uptake in renal epithelial cells of the proximal tubule.
肾脏通过释放血管活性物质和尿钠排泄在血压控制中发挥核心作用。原发性高血压患者通常表现为持续性高血压并伴有钠潴留。L-二羟基苯丙氨酸(L-DOPA)是一种氨基酸,可被芳香族L-氨基酸脱羧酶转化为多巴胺。肾脏近端肾小管上皮细胞对L-DOPA的摄取受L型氨基酸转运体2(LAT2)控制。LAT2属于氨基酸转运体的溶质载体家族7(SLC7),由SLC7A8基因编码。在自发性高血压大鼠的二级肠系膜动脉和肾脏中,SLC7A8的表达增加。本研究旨在探讨SLC7A8基因在肾细胞处理L-DOPA中的生理作用。通过对保留近端肾小管上皮细胞若干特性的NRK-52E细胞进行腺病毒转导,实现了SLC7A8 mRNA和蛋白水平选择性上调。此外,使用高效液相色谱法测定L-DOPA摄取;表达SLC7A8的NRK-52E细胞对L-DOPA的摄取增加。本研究结果表明,SLC7A8可能通过调节近端肾小管肾上皮细胞对L-DOPA的摄取在血压控制中发挥关键作用。