Key result
SLC7A8 upregulation significantly increases renal tubular L-DOPA uptake in vitro.
Why the study?
The physiological role of the SLC7A8 gene in L-DOPA handling by kidney proximal tubular epithelial cells and its impact on blood pressure control was unclear.
p-value: p=<0.05
SLC7A8 upregulation may enhance renal L-DOPA uptake; leaves open any role in human hypertension or therapeutic targeting.
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.
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Wu et al. (2017) studied Essential hypertension (n=10). Adenoviral transduction of SLC7A8 (pAdxsi-GFP-SLC7A8) vs. Blank control (untransduced) and negative control (empty vector) was evaluated on L-DOPA uptake in NRK-52E cells (p=<0.05). Adenoviral-mediated upregulation of SLC7A8 expression in NRK-52E renal tubular epithelial cells significantly increased L-DOPA uptake compared to blank and negative controls.
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