Increased SLC7A8 expression mediates L-DOPA uptake by renal tubular epithelial cells

Wu,Yihao; Yin,Qiqi; Lin,Su; Huang,Xiaoyan; Xia,Quan; Chen,Zhe; Zhang,Xingwei; Yang,Deye

doi:10.3892/mmr.2017.6620

Increased SLC7A8 expression mediates L-DOPA uptake by renal tubular epithelial cells

Authors:
- Yihao Wu
- Qiqi Yin
- Su Lin
- Xiaoyan Huang
- Quan Xia
- Zhe Chen
- Xingwei Zhang
- Deye Yang
View Affiliations

Affiliations: 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, Division of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China
Published online on: May 25, 2017 https://doi.org/10.3892/mmr.2017.6620
Pages: 887-893

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

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.

View Figures

View References

1	Sun H, Yang ZQ, Liu SY, Yu L, Huang K, Lin KQ, Chu JY and Huang XQ: Correlation between natriuretic peptide receptor C (NPR3) gene polymorphisms and hypertension in the Dai people of China. Genet Mol Res. 14:8786–8795. 2015. View Article : Google Scholar : PubMed/NCBI
2	Pinto V, Pinho MJ and Soares-da-Silva P: Renal amino acid transport systems and essential hypertension. FASEB J. 27:2927–2938. 2013. View Article : Google Scholar : PubMed/NCBI
3	Moura E, Silva E, Serrão MP, Afonso J, Kozmus CE and Vieira-Coelho MA: α2C-Adrenoceptors modulate L-DOPA uptake in opossum kidney cells and in the mouse kidney. Am J Physiol Renal Physiol. 303:F928–F938. 2012. View Article : Google Scholar : PubMed/NCBI
4	Camargo SM, Vuille-dit-Bille RN, Mariotta L, Ramadan T, Huggel K, Singer D, Götze O and Verrey F: The molecular mechanism of intestinal levodopa absorption and its possible implications for the treatment of Parkinson's disease. J Pharmacol Exp Ther. 351:114–123. 2014. View Article : Google Scholar : PubMed/NCBI
5	del Amo EM, Urtti A and Yliperttula M: Pharmacokinetic role of L-type amino acid transporters LAT1 and LAT2. Eur J Pharm Sci. 35:161–174. 2008. View Article : Google Scholar : PubMed/NCBI
6	Huang X, Wang B, Yang D, Shi X, Hong J, Wang S, Dai X, Zhou X and Geng YJ: Reduced expression of FXYD domain containing ion transport regulator 5 in association with hypertension. Int J Mol Med. 29:231–238. 2012.PubMed/NCBI
7	Chen K, Deng K, Wang X, Wang Z, Zheng S, Ren H, He D, Han Y, Asico LD, Jose PA and Zeng C: Activation of D4 dopamine receptor decreases angiotensin II type 1 receptor expression in rat renal proximal tubule cells. Hypertension. 65:153–160. 2015. View Article : Google Scholar : PubMed/NCBI
8	Igreja B, Pires NM, Bonifácio MJ, Loureiro AI, Fernandes-Lopes C, Wright LC and Soares-da-Silva P: Blood pressure-decreasing effect of etamicastat alone and in combination with antihypertensive drugs in the spontaneously hypertensive rat. Hypertens Res. 38:30–38. 2015. View Article : Google Scholar : PubMed/NCBI
9	Vieira-Coelho MA, Serrão P, Hussain T, Lokhandwala MF and Soares-da-Silva P: Salt intake and intestinal dopaminergic activity in adult and old Fischer 344 rats. Life Sci. 69:1957–1968. 2001. View Article : Google Scholar : PubMed/NCBI
10	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
11	Wan TT, Li XF, Sun YM, Li YB and Su Y: Role of the calpain on the development of diabetes mellitus and its chronic complications. Biomed Pharmacother. 74:187–190. 2015. View Article : Google Scholar : PubMed/NCBI
12	Siklos M, BenAissa M and Thatcher GR: Cysteine proteases as therapeutic targets: Does selectivity matter? A systematic review of calpain and cathepsin inhibitors. Acta Pharm Sin B. 5:506–519. 2015. View Article : Google Scholar : PubMed/NCBI
13	Kawada N, Kristensen DB, Asahina K, Nakatani K, Minamiyama Y, Seki S and Yoshizato K: Characterization of a stellate cell activation-associated protein (STAP) with peroxidase activity found in rat hepatic stellate cells. J Biol Chem. 276:25318–25323. 2001. View Article : Google Scholar : PubMed/NCBI
14	Ostendorf T, Boor P, van Roeyen CR and Floege J: Platelet-derived growth factors (PDGFs) in glomerular and tubulointerstitial fibrosis. Kidney Int Suppl (2011). 4:65–69. 2014. View Article : Google Scholar : PubMed/NCBI
15	Leask A: Getting to the heart of the matter: New insights into cardiac fibrosis. Circ Res. 116:1269–1276. 2015. View Article : Google Scholar : PubMed/NCBI
16	Fotiadis D, Kanai Y and Palacin M: The SLC3 and SLC7 families of amino acid transporters. Mol Aspects Med. 34:139–158. 2013. View Article : Google Scholar : PubMed/NCBI
17	Schweikhard ES and Ziegler CM: Amino acid secondary transporters: Toward a common transport mechanism. Curr Top Membr. 70:1–281. 2012. View Article : Google Scholar : PubMed/NCBI
18	Closs EI, Boissel JP, Habermeier A and Rotmann A: Structure and function of cationic amino acid transporters (CATs). J Membr Biol. 213:67–77. 2006. View Article : Google Scholar : PubMed/NCBI
19	Pinho MJ, Gomes P, Serrão MP, Bonifácio MJ and Soares-da-Silva P: Organ-specific overexpression of renal LAT2 and enhanced tubular L-DOPA uptake precede the onset of hypertension. Hypertension. 42:613–618. 2003. View Article : Google Scholar : PubMed/NCBI
20	Pinho MJ, Serrão MP, Gomes P, Hopfer U, Jose PA and Soares-da-Silva P: Over-expression of renal LAT1 and LAT2 and enhanced L-DOPA uptake in SHR immortalized renal proximal tubular cells. Kidney Int. 66:216–226. 2004. View Article : Google Scholar : PubMed/NCBI
21	Soares-da-Silva P and Serrão MP: High- and low-affinity transport of L-leucine and L-DOPA by the hetero amino acid exchangers LAT1 and LAT2 in LLC-PK1 renal cells. Am J Physiol Renal Physiol. 287:F252–F261. 2004. View Article : Google Scholar : PubMed/NCBI
22	Sizova D, Velazquez H, Sampaio-Maia B, Quelhas-Santos J, Pestana M and Desir GV: Renalase regulates renal dopamine and phosphate metabolism. Am J Physiol Renal Physiol. 305:F839–F844. 2013. View Article : Google Scholar : PubMed/NCBI
23	Ishiia H, Sasaki Y, Goshima Y, Kanai Y, Endou H, Ayusawa D, Ono H, Miyamae T and Misu Y: Involvement of rBAT in Na(+)-dependent and -independent transport of the neurotransmitter candidate L-DOPA in Xenopus laevis oocytes injected with rabbit small intestinal epithelium poly A(+) RNA. Biochim Biophys Acta. 1466:61–70. 2000. View Article : Google Scholar : PubMed/NCBI
24	Kageyama T, Nakamura M, Matsuo A, Yamasaki Y, Takakura Y, Hashida M, Kanai Y, Naito M, Tsuruo T, Minato N and Shimohama S: The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier. Brain Res. 879:115–121. 2000. View Article : Google Scholar : PubMed/NCBI
25	Gomes P and Soares-da-Silva P: Na+-independent transporters, LAT-2 and b0,+,exchange L-DOPA with neutral and basic amino acids in two clonal renal cell lines. J Membr Biol. 186:63–80. 2002. View Article : Google Scholar : PubMed/NCBI
26	Soares-Da-Silva P, Serrão MP, Pinho MJ and Bonifácio MJ: Cloning and gene silencing of LAT2, the L-3,4-dihydroxyphenylalanine (L-DOPA) transporter, in pig renal LLC-PK1 epithelial cells. FASEB J. 18:1489–1498. 2004. View Article : Google Scholar : PubMed/NCBI
27	Pinho MJ, Serrão MP and Soares-da-Silva P: High-salt intake and the renal expression of amino acid transporters in spontaneously hypertensive rats. Am J Physiol Renal Physiol. 292:F1452–F1463. 2007. View Article : Google Scholar : PubMed/NCBI
28	Chen Y, Asico LD, Zheng S, Villar VA, He D, Zhou L, Zeng C and Jose PA: Gastrin and D1 dopamine receptor interact to induce natriuresis and diuresis. Hypertension. 62:927–933. 2013. View Article : Google Scholar : PubMed/NCBI