Overexpression of non-functional LAT1/4F2hc in renal proximal tubular epithelial cells from the spontaneous hypertensive rat

• Type: Article in International Scientific Journal
• Date: 2007

Authors

Maria João Pinho (Author) FMUP; Maria Paula Serrão (Author) FMUP; Pedro A Jose (Author) Other; Patrício Soares da Silva (Author) FMUP

Journal

Title: Cellular Physiology and Biochemistry

Vol. 20

Pages: 535-548

ISSN: 1015-8987

Publisher: Cell Physiol Biochem Press

Indexing

ISI Web of Knowledge - 2 Citations

Scopus - 2 Citations

Pubmed / Medline

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-004-CP5

DOI: 10.1159/000107537

Abstract (EN): The present study examined the expression of type 1 L- amino acid transporter ( LAT1) and its associated glycoprotein 4F2hc in freshly isolated renal proximal tubules and immortalized renal proximal tubular epithelial ( PTE) cells from spontaneously hypertensive ( SHR) and normotensive ( WKY) rats. The study also examined the inward and outward transport of [ C-14]- L- leucine, the preferred substrate of LAT1. The abundance of LAT1 and 4F2hc was greater in SHR than in WKY, both in freshly isolated renal proximal tubules and immortalized renal proximal tubular cells. In the absence of extracellular Na+ the BCH ( 2- aminobicyclo( 2,2,1)- heptane- 2- carboxylic acid)- sensitive [ C-14]- L- leucine uptake in SHR PTE cells was similar to 50% that observed in WKY PTE cells ( 77 +/- 4 vs 164 +/- 7 pmol/ mg protein). In the absence of extracellular Na+ the affinity of the transporter for the substrate in WKY PTE cells was 7.7- fold that in SHR cells, as evidenced by lower K-0.5 values. Gene silencing with a LAT1 siRNA and a 4F2hc siRNA signficantly reduced LAT1 and 4F2hc expression, which was accompanied by a marked reduction in Na+independent [ C-14]- L- leucine uptake in both SHR and WKY PTE cells. The spontaneous and L- leucine-stimulated outward transfer of [ C-14]- L- leucine was Na+independent in both SHR and WKY PTE cells. The spontaneous [ C-14]- L- leucine efflux was higher in WKY than in SHR PTE cells and the potency of L- leucine to stimulate [ 14C]- L- leucine efflux in WKY ( EC50 = 9 mu M) was greater than in SHR PTE cells ( EC50 = 41 mu M). It is concluded that the SHR kidney overexpress LAT1/ 4F2hc units which display low affinity for L- leucine transport.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14