Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Pflugers Arch
2009 Oct 01;4586:1163-73. doi: 10.1007/s00424-009-0692-9.
Show Gene links
Show Anatomy links
Arginine transport in human erythroid cells: discrimination of CAT1 and 4F2hc/y+LAT2 roles.
Rotoli BM
,
Closs EI
,
Barilli A
,
Visigalli R
,
Simon A
,
Habermeier A
,
Bianchi N
,
Gambari R
,
Gazzola GC
,
Bussolati O
,
Dall'Asta V
.
???displayArticle.abstract???
Since arginine metabolites, such as nitric oxide and polyamines, influence the expression of genes involved in erythroid differentiation, the transport of the cationic amino acid may play an important role in erythroid cells. However, available data only concern the presence in these cells of CAT1 transporter (system y(+)), while no information exists on the role of the heterodimeric transporters of system y(+)L (4F2hc/y(+)LAT1 and 4F2hc/y(+)LAT2) which operates transmembrane arginine fluxes cis-inhibited by neutral amino acids in the presence of sodium. Using erythroleukemia K562 cells and normal erythroid precursors, we demonstrate here that arginine transport in human erythroid cells is due to the additive contributions of a leucine-sensitive and leucine-insensitive component. In both cell types, leucine inhibition of arginine influx is much less evident in the absence of sodium, a hallmark of system y(+)L. In K562 cells, N-ethylmaleimide, a known inhibitor of CAT transporters (system y(+)), suppresses only a fraction of arginine influx corresponding to leucine-insensitive uptake. Moreover, in Xenopus oocytes coexpressing 4F2hc and y(+)LAT2, leucine exerts a marked inhibition of arginine transport, partially dependent on sodium, while no inhibition is seen in oocytes expressing CAT1. Lastly, silencing of SLC7A6, the gene for y(+)LAT2, lowers arginine transport and doubles the intracellular content of the cationic amino acid in K562 cells. We conclude that arginine transport in human erythroid cells is due to both system y(+) (CAT1 transporter) and system y(+)L (4F2hc/y(+)LAT2 isoform), which mainly contribute, respectively, to the influx and to the efflux of the cationic amino acid.
Almeida,
Erythrocyte L-arginine uptake in peritoneal dialysis patients changes over time.
2007, Pubmed
Almeida,
Erythrocyte L-arginine uptake in peritoneal dialysis patients changes over time.
2007,
Pubmed
Bröer,
Amino acid transport across mammalian intestinal and renal epithelia.
2008,
Pubmed
Bröer,
The heterodimeric amino acid transporter 4F2hc/y+LAT2 mediates arginine efflux in exchange with glutamine.
2000,
Pubmed
,
Xenbase
Bronte,
L-arginine metabolism in myeloid cells controls T-lymphocyte functions.
2003,
Pubmed
Chasis,
Erythroblastic islands: niches for erythropoiesis.
2008,
Pubmed
Choi,
Differential impact of L-arginine deprivation on the activation and effector functions of T cells and macrophages.
2009,
Pubmed
Cokic,
Hydroxyurea induces fetal hemoglobin by the nitric oxide-dependent activation of soluble guanylyl cyclase.
2003,
Pubmed
Cokic,
Hydroxyurea nitrosylates and activates soluble guanylyl cyclase in human erythroid cells.
2008,
Pubmed
Dall'Asta,
Arginine transport through system y(+)L in cultured human fibroblasts: normal phenotype of cells from LPI subjects.
2000,
Pubmed
Dall'Asta,
Amino acids are compatible osmolytes for volume recovery after hypertonic shrinkage in vascular endothelial cells.
1999,
Pubmed
Devés,
Transporters for cationic amino acids in animal cells: discovery, structure, and function.
1998,
Pubmed
,
Xenbase
Devés,
Identification of a new transport system (y+L) in human erythrocytes that recognizes lysine and leucine with high affinity.
1992,
Pubmed
Devés,
N-ethylmaleimide discriminates between two lysine transport systems in human erythrocytes.
1993,
Pubmed
Fibach,
Mithramycin induces fetal hemoglobin production in normal and thalassemic human erythroid precursor cells.
2003,
Pubmed
Gambari,
Medicinal chemistry of fetal hemoglobin inducers for treatment of beta-thalassemia.
2007,
Pubmed
Haynes,
Zileuton induces hemoglobin F synthesis in erythroid progenitors: role of the L-arginine-nitric oxide signaling pathway.
2004,
Pubmed
Ikuta,
Mechanism for fetal globin gene expression: role of the soluble guanylate cyclase-cGMP-dependent protein kinase pathway.
2001,
Pubmed
Kern,
Arginase induction by sodium phenylbutyrate in mouse tissues and human cell lines.
2007,
Pubmed
Kleinbongard,
Red blood cells express a functional endothelial nitric oxide synthase.
2006,
Pubmed
Lozzio,
Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome.
1975,
Pubmed
Maeda,
Role of polyamines derived from arginine in differentiation and proliferation of human blood cells.
2006,
Pubmed
Peller,
Identification of gene networks associated with erythroid differentiation.
2009,
Pubmed
Perkins,
Anemia and perinatal death result from loss of the murine ecotropic retrovirus receptor mCAT-1.
1997,
Pubmed
Rotmann,
Intracellular accumulation of L-Arg, kinetics of transport, and potassium leak conductance in oocytes from Xenopus laevis expressing hCAT-1, hCAT-2A, and hCAT-2B.
2004,
Pubmed
,
Xenbase
Rotoli,
Alveolar macrophages from normal subjects lack the NOS-related system y+ for arginine transport.
2007,
Pubmed
Rotoli,
INFgamma stimulates arginine transport through system y+L in human monocytes.
2004,
Pubmed
Rotoli,
The transport of cationic amino acids in human airway cells: expression of system y+L activity and transepithelial delivery of NOS inhibitors.
2005,
Pubmed
Sala,
Two-way arginine transport in human endothelial cells: TNF-alpha stimulation is restricted to system y(+).
2002,
Pubmed
Shima,
L-arginine import via cationic amino acid transporter CAT1 is essential for both differentiation and proliferation of erythrocytes.
2006,
Pubmed
Verrey,
CATs and HATs: the SLC7 family of amino acid transporters.
2004,
Pubmed
Visigalli,
Rapamycin stimulates arginine influx through CAT2 transporters in human endothelial cells.
2007,
Pubmed
