cationic amino acid transporter 1


Summary: A high-affinity, low capacity system y+ amino acid transporter found ubiquitously. It has specificity for the transport of ARGININE; LYSINE; and ORNITHINE. It may also act as an ecotropic leukemia retroviral receptor.

Top Publications

  1. Vásquez G, Sanhueza F, Vásquez R, Gonzalez M, San Martín R, Casanello P, et al. Role of adenosine transport in gestational diabetes-induced L-arginine transport and nitric oxide synthesis in human umbilical vein endothelium. J Physiol. 2004;560:111-22 pubmed
    ..diabetes is associated with activation of these purinoceptors or altered expression of human cationic amino acid transporter 1 (hCAT-1) or human equilibrative nucleoside transporter 1 (hENT1), or endothelial NO synthase (eNOS) ..
  2. Strobel J, Mieth M, Endress B, Auge D, Konig J, Fromm M, et al. Interaction of the cardiovascular risk marker asymmetric dimethylarginine (ADMA) with the human cationic amino acid transporter 1 (CAT1). J Mol Cell Cardiol. 2012;53:392-400 pubmed publisher
    ..Our aim was to investigate the cellular uptake properties of ADMA by the human cationic amino acid transporter 1 (CAT1; SLC7A1)...
  3. Casanello P, Sobrevia L. Intrauterine growth retardation is associated with reduced activity and expression of the cationic amino acid transport systems y+/hCAT-1 and y+/hCAT-2B and lower activity of nitric oxide synthase in human umbilical vein endothelial cells. Circ Res. 2002;91:127-34 pubmed
    ..Alterations in L-arginine/NO pathway could be critical for the physiological processes involved in the etiology of IUGR in human pregnancies. ..
  4. Gonzalez M, Gallardo V, Rodriguez N, Salomon C, Westermeier F, Guzman Gutierrez E, et al. Insulin-stimulated L-arginine transport requires SLC7A1 gene expression and is associated with human umbilical vein relaxation. J Cell Physiol. 2011;226:2916-24 pubmed publisher
    ..nitric oxide (NO)-dependent vascular relaxation, and increases L-arginine transport via cationic amino acid transporter 1 (hCAT-1) and endothelial NO synthase (eNOS) expression and activity in human umbilical vein ..
  5. Hammermann R, Brunn G, Racke K. Analysis of the genomic organization of the human cationic amino acid transporters CAT-1, CAT-2 and CAT-4. Amino Acids. 2001;21:211-9 pubmed
    ..hCAT-4 consists of only 4 translated exons and 3 short introns. Exons of identical size and highly homologous to exon 3 of hCAT-4 are present in hCAT-1 and hCAT-2. ..
  6. Vásquez R, Farias M, Vega J, Martin R, Vecchiola A, Casanello P, et al. D-glucose stimulation of L-arginine transport and nitric oxide synthesis results from activation of mitogen-activated protein kinases p42/44 and Smad2 requiring functional type II TGF-beta receptors in human umbilical vein endothelium. J Cell Physiol. 2007;212:626-32 pubmed
    ..Thus, TGF-beta1 could play a crucial role under conditions of hyperglycemia, such as gestational diabetes mellitus, which is associated with fetal endothelial dysfunction. ..
  7. Fujisawa R, Masuda M. Ecotropic murine leukemia virus envelope protein affects interaction of cationic amino acid transporter 1 with clathrin adaptor protein complexes, leading to receptor downregulation. Virology. 2007;368:342-50 pubmed publisher
    Mouse cationic amino acid transporter 1 (mCAT1) serves as the receptor for ecotropic murine leukemia virus (eMuLV). It has been shown that mCAT1 is expressed on the basolateral surface of polarized epithelial MDCK cells...
  8. Kubo Y, Ono T, Ogura M, Ishimoto A, Amanuma H. A glycosylation-defective variant of the ecotropic murine retrovirus receptor is expressed in rat XC cells. Virology. 2002;303:338-44 pubmed
    ..However, xcCAT1-expressing CHO cells did not fuse with 293T cells expressing R+ Env, indicating that xcCAT1 expression is not sufficient to induce the XC cell-specific characteristic of forming syncytia in response to R+ Env. ..
  9. Jaeger K, Paulsen F, Wohlrab J. Characterization of cationic amino acid transporters (hCATs) 1 and 2 in human skin. Histochem Cell Biol. 2008;129:321-9 pubmed publisher

More Information


  1. Cui Z, Tuladhar R, Hart S, Marber M, Pearson J, Baydoun A. Rate of transport of l-arginine is independent of the expression of inducible nitric oxide synthase in HEK 293 cells. Nitric Oxide. 2005;12:21-30 pubmed
  2. Rotmann A, Vékony N, Gassner D, Niegisch G, Strand D, Martine U, et al. Activation of classical protein kinase C reduces the expression of human cationic amino acid transporter 3 (hCAT-3) in the plasma membrane. Biochem J. 2006;395:117-23 pubmed
    ..shown that activation of PKC (protein kinase C) results in internalization of hCAT-1 [human CAT-1 (cationic amino acid transporter 1)] and a decrease in arginine transport [Rotmann, Strand, Martiné and Closs (2004) J. Biol. Chem...
  3. Recker K, Klapperstück T, Kehlen A, Wohlrab J. The importance of cationic amino acid transporter expression in human skin. J Invest Dermatol. 2003;121:1552-3 pubmed
  4. Bauer B, Isom S, Spate L, Whitworth K, Spollen W, Blake S, et al. Transcriptional profiling by deep sequencing identifies differences in mRNA transcript abundance in in vivo-derived versus in vitro-cultured porcine blastocyst stage embryos. Biol Reprod. 2010;83:791-8 pubmed publisher
    ..Illumina sequencing and alignment to a custom transcriptome identified a large number of genes that yield clues on ways to manipulate the culture media to mimic the in vivo environment. ..
  5. Pan C, Lou L, Huo Y, Singh G, Chen M, Zhang D, et al. Salvianolic acid B and tanshinone IIA attenuate myocardial ischemia injury in mice by NO production through multiple pathways. Ther Adv Cardiovasc Dis. 2011;5:99-111 pubmed publisher
  6. Lu Y, Wang W, Wang J, Yang C, Mao H, Fu X, et al. Overexpression of arginine transporter CAT-1 is associated with accumulation of L-arginine and cell growth in human colorectal cancer tissue. PLoS ONE. 2013;8:e73866 pubmed publisher
    ..Our results may be useful for the development of molecular diagnostic tools and targeted therapy for colorectal cancer. ..
  7. Schwartz I, Davidovitz A, Chernichovski T, Levin Iaina N, Guzner Gur H, Levo Y, et al. Arginine transport is augmented, through modulation of cationic amino acid transporter-1, in obstructive uropathy in rats. Kidney Blood Press Res. 2008;31:210-6 pubmed publisher
    ..BUO induces an increase in glomerular arginine transport via upregulation of CAT-1, probably due to increase in arginine utilization by a non-NO pathway. ..
  8. Jopling C, Norman K, Sarnow P. Positive and negative modulation of viral and cellular mRNAs by liver-specific microRNA miR-122. Cold Spring Harb Symp Quant Biol. 2006;71:369-76 pubmed
    ..The positive role of miR-122 in viral replication suggests that this miRNA could be targeted for antiviral therapy. ..
  9. Bruno I, Wilkinson M. P-bodies react to stress and nonsense. Cell. 2006;125:1036-8 pubmed
    ..2006) reveal that normal mRNA can be released from P-bodies and translated into protein in response to stress. Meanwhile, Sheth and Parker (2006) report that aberrant mRNAs are targeted to P-bodies to undergo rapid decay. ..
  10. Cui H, Chen B, Chicoine L, Nelin L. Overexpression of cationic amino acid transporter-1 increases nitric oxide production in hypoxic human pulmonary microvascular endothelial cells. Clin Exp Pharmacol Physiol. 2011;38:796-803 pubmed publisher
    ..We speculate that the CAT may represent a novel therapeutic target for treating pulmonary hypertensive disorders. ..
  11. Guzman Gutierrez E, Westermeier F, Salomon C, Gonzalez M, Pardo F, Leiva A, et al. Insulin-increased L-arginine transport requires A(2A) adenosine receptors activation in human umbilical vein endothelium. PLoS ONE. 2012;7:e41705 pubmed publisher
    ..Thus, insulin modulation of hCAT-1 expression and activity requires functional A(2A)AR in HUVECs, a mechanism that may be applicable to diseases associated with fetal insulin resistance, such as gestational diabetes. ..
  12. Gilles W, Vulcu S, Liewald J, Habermeier A, Vékony N, Closs E, et al. Monovalent cation conductance in Xenopus laevis oocytes expressing hCAT-3. Biochim Biophys Acta. 2005;1668:234-9 pubmed
    ..It is concluded that hCAT-3 is a passive transport system that conducts monovalent cations including L-Arg. The particular role of hCAT-3 in the diverse tissues remains to be elucidated. ..
  13. Bhattacharyya S, Habermacher R, Martine U, Closs E, Filipowicz W. Relief of microRNA-mediated translational repression in human cells subjected to stress. Cell. 2006;125:1111-24 pubmed
    ..Here we show that cationic amino acid transporter 1 (CAT-1) mRNA and reporters bearing its 3'UTR can be relieved from the microRNA miR-122-induced ..
  14. Schwartz D, Schwartz I, Gnessin E, Wollman Y, Chernichovsky T, Blum M, et al. Differential regulation of glomerular arginine transporters (CAT-1 and CAT-2) in lipopolysaccharide-treated rats. Am J Physiol Renal Physiol. 2003;284:F788-95 pubmed
    ..These results may correspond to the changes in glomerular iNOS and eNOS activity in sepsis. ..
  15. Sáenz D, Cymeryng C, De Nichilo A, Sacca G, Keller Sarmiento M, Rosenstein R. Photic regulation of L-arginine uptake in the golden hamster retina. J Neurochem. 2002;80:512-9 pubmed
    ..Based on these results, it might be presumed that hamster retinal L-arginine uptake is regulated by the photic stimulus. ..
  16. Kaye D, Parnell M, Ahlers B. Reduced myocardial and systemic L-arginine uptake in heart failure. Circ Res. 2002;91:1198-203 pubmed
    ..These data indicate the presence of a significant reduction in the myocardial uptake of L-arginine in patients with CHF. Furthermore, this abnormality seems to be part of a systemic downregulation of L-arginine transport. ..
  17. Speake P, Glazier J, Ayuk P, Reade M, Sibley C, D Souza S. L-Arginine transport across the basal plasma membrane of the syncytiotrophoblast of the human placenta from normal and preeclamptic pregnancies. J Clin Endocrinol Metab. 2003;88:4287-92 pubmed
    ..If reflected in vivo, a similar increase in transporter activity could alter the delivery of L-arginine to syncytiotrophoblast eNOS. ..
  18. Yaman I, Fernandez J, Liu H, Caprara M, Komar A, Koromilas A, et al. The zipper model of translational control: a small upstream ORF is the switch that controls structural remodeling of an mRNA leader. Cell. 2003;113:519-31 pubmed
    ..This study suggests that the structure of the IRES is dynamic and regulation of this RNA structure is a mechanism of translational control. ..
  19. Furesz T, Heath Monnig E, Kamath S, Smith C. Lysine uptake by cloned hCAT-2B: comparison with hCAT-1 and with trophoblast surface membranes. J Membr Biol. 2002;189:27-33 pubmed
    ..The identification and characterization of the various cationic amino-acid transporters of the human placenta have the potential to increase the understanding of the cellular mechanism of transplacental transfer. ..
  20. Sobrevia L, Gonzalez M. A role for insulin on L-arginine transport in fetal endothelial dysfunction in hyperglycaemia. Curr Vasc Pharmacol. 2009;7:467-74 pubmed
    ..Thus, a role for these transcription factors in response to insulin is proposed in fetal endothelial cells exposed to hyperglycaemia. ..
  21. Chicoine L, Chicione L, Stenger M, Cui H, Calvert A, Evans R, et al. Nitric oxide suppression of cellular proliferation depends on cationic amino acid transporter activity in cytokine-stimulated pulmonary endothelial cells. Am J Physiol Lung Cell Mol Physiol. 2011;300:L596-604 pubmed publisher
    ..We speculate that CAT activity may represent a novel therapeutic target in inflammatory lung diseases characterized by NO overproduction. ..
  22. Ingbir M, Schwartz I, Shtabsky A, Filip I, Reshef R, Chernichovski T, et al. Rosiglitazone improves aortic arginine transport, through inhibition of PKCalpha, in uremic rats. Am J Physiol Renal Physiol. 2008;295:F471-7 pubmed publisher
    ..These findings are associated with restoration of eNO generation and attenuation of protein nitration and therefore may serve as a novel mechanism to explain the beneficial effects of rosiglitazone on endothelial function in uremia. ..
  23. Yan Y, Kozak C. Novel postentry resistance to AKV ecotropic mouse gammaretroviruses in the African pygmy mouse, Mus minutoides. J Virol. 2008;82:6120-9 pubmed publisher
    ..M. minutoides cells thus have a novel postentry resistance to AKV MLVs. ..
  24. Czapiga M, Colton C. Microglial function in human APOE3 and APOE4 transgenic mice: altered arginine transport. J Neuroimmunol. 2003;134:44-51 pubmed
    ..This change in microglial arginine transport suggests a potential impact of the APOE4 gene allele on those biochemical pathways such as NO production or cell proliferation to which arginine contributes. ..
  25. Flores C, Rojas S, Aguayo C, Parodi J, Mann G, Pearson J, et al. Rapid stimulation of L-arginine transport by D-glucose involves p42/44(mapk) and nitric oxide in human umbilical vein endothelium. Circ Res. 2003;92:64-72 pubmed
    ..This could be determinant in pathologies in which rapid fluctuations of plasma D-glucose may occur and may underlie the reported vasodilatation in early stages of diabetes mellitus. ..
  26. Jin L, Caldwell R, Li Masters T, Caldwell R. Homocysteine induces endothelial dysfunction via inhibition of arginine transport. J Physiol Pharmacol. 2007;58:191-206 pubmed
    ..Reduced arginine supply may lead to eNOS uncoupling and generation of superoxide, contributing to HCY-induced oxidative stress. ..
  27. Yamaguchi S, Hasegawa M, Suzuki T, Ikeda H, Aizawa S, Hirokawa K, et al. In vivo distribution of receptor for ecotropic murine leukemia virus and binding of envelope protein of Friend Murine leukemia virus. Arch Virol. 2003;148:1175-84 pubmed
  28. Bhattacharyya S, Habermacher R, Martine U, Closs E, Filipowicz W. Stress-induced reversal of microRNA repression and mRNA P-body localization in human cells. Cold Spring Harb Symp Quant Biol. 2006;71:513-21 pubmed
    ..Here, we show that cationic amino acid transporter 1 (CAT-1) mRNA and reporters bearing the CAT-1 3'UTR or its fragments can be relieved from the miRNA ..
  29. Yang Z, Venardos K, Jones E, Morris B, Chin Dusting J, Kaye D. Identification of a novel polymorphism in the 3'UTR of the L-arginine transporter gene SLC7A1: contribution to hypertension and endothelial dysfunction. Circulation. 2007;115:1269-74 pubmed
    ..As such, this polymorphism may account for the apparent link between altered endothelial function, L-arginine, and nitric oxide metabolism and predisposition to essential hypertension. ..
  30. Lopez A, Wang C, Huang C, Yaman I, Li Y, Chakravarty K, et al. A feedback transcriptional mechanism controls the level of the arginine/lysine transporter cat-1 during amino acid starvation. Biochem J. 2007;402:163-73 pubmed
    ..These results suggest that the transient increase in cat-1 transcription is due to transcriptional activation caused by ATF4 followed by transcriptional repression by ATF3 via a feedback mechanism. ..
  31. Fernandez J, Lopez A, Wang C, Mishra R, Zhou L, Yaman I, et al. Transcriptional control of the arginine/lysine transporter, cat-1, by physiological stress. J Biol Chem. 2003;278:50000-9 pubmed
    ..Our studies show that the increase in cat-1 gene expression by cellular stress involves at least three types of coordinate regulation: regulation of transcription, regulation of mRNA stability, and regulation of mRNA translation. ..
  32. Murphy S, Chung Landers M, Honczarenko M, Gaulton G. Linkage of reduced receptor affinity and superinfection to pathogenesis of TR1.3 murine leukemia virus. J Virol. 2006;80:4601-9 pubmed
  33. Yaman I, Fernandez J, Sarkar B, Schneider R, Snider M, Nagy L, et al. Nutritional control of mRNA stability is mediated by a conserved AU-rich element that binds the cytoplasmic shuttling protein HuR. J Biol Chem. 2002;277:41539-46 pubmed
    ..It is proposed that an adaptive response of cells to nutritional stress results in increased mRNA stability mediated by HuR binding to the NS-ARE. ..
  34. Rotmann A, Closs E, Liewald J, Nawrath H. 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. Biochim Biophys Acta. 2004;1660:138-43 pubmed
    ..Conductance measurements at symmetric concentrations of L-Arg (inside/outside) allowed us to determine KM and Vmax. The empty transporter of hCAT-2B featured an unexpected potassium conductance, which was inhibited by L-Arg. ..
  35. Nelin L, Krenz G, Chicoine L, Dawson C, Schapira R. L-Arginine uptake and metabolism following in vivo silica exposure in rat lungs. Am J Respir Cell Mol Biol. 2002;26:348-55 pubmed
    ..We conclude that the increase in NO production in silica-exposed lungs was associated with increased L-arg uptake from the vasculature, presumably resulting from increased CAT-1 and CAT-2, and by increased L-arg metabolism via arginase. ..
  36. Abdelmagid S, Rickard J, McDonald W, Thomas L, Too C. CAT-1-mediated arginine uptake and regulation of nitric oxide synthases for the survival of human breast cancer cell lines. J Cell Biochem. 2011;112:1084-92 pubmed publisher
    ..In summary, several CAT isoforms are expressed in breast cancer cells. The CAT-1 isoform plays a role in arginine uptake and, together with PRL/E2-induced NOS, contribute to NO production for the survival of MCF-7 and T47D cells. ..
  37. Bernstein H, Stich C, Jäger K, Dobrowolny H, Wick M, Steiner J, et al. Agmatinase, an inactivator of the putative endogenous antidepressant agmatine, is strongly upregulated in hippocampal interneurons of subjects with mood disorders. Neuropharmacology. 2012;62:237-46 pubmed publisher
    ..The reported increased expression of agmatinase suggests a functional relevance of the enzyme in the pathophysiology of human affective disorders. This article is part of a Special Issue entitled 'Anxiety and Depression'. ..
  38. Schwartz I, Hershkovitz R, Iaina A, Gnessin E, Wollman Y, Chernichowski T, et al. Garlic attenuates nitric oxide production in rat cardiac myocytes through inhibition of inducible nitric oxide synthase and the arginine transporter CAT-2 (cationic amino acid transporter-2). Clin Sci (Lond). 2002;102:487-93 pubmed
  39. Tain Y, Chen C, Lee C, Kao Y, Sheen J, Yu H, et al. Melatonin regulates L-arginine transport and NADPH oxidase in young rats with bile duct ligation: role of protein kinase C. Pediatr Res. 2013;73:395-401 pubmed publisher
    ..Melatonin inhibits PKC-? to increase cationic amino acid transporter-1 (CAT-1)-mediated L-arginine uptake in BDL liver, whereas it inhibits PKC-? to reduce NADPH-dependent superoxide production. ..
  40. Schafer S, Wallerath T, Closs E, Schmidt C, Schwarz P, Forstermann U, et al. Dexamethasone suppresses eNOS and CAT-1 and induces oxidative stress in mouse resistance arterioles. Am J Physiol Heart Circ Physiol. 2005;288:H436-44 pubmed
  41. Scalera F, Closs E, Flick E, Martens Lobenhoffer J, Boissel J, Lendeckel U, et al. Paradoxical effect of L-arginine: acceleration of endothelial cell senescence. Biochem Biophys Res Commun. 2009;386:650-5 pubmed publisher
    ..The most possible explanation for the paradoxical acceleration of senescence by L-arginine so far may be the translational and posttranslational activation of arginase II. ..
  42. Chan C, Ramirez Montealegre D, Pearce D. Altered arginine metabolism in the central nervous system (CNS) of the Cln3-/- mouse model of juvenile Batten disease. Neuropathol Appl Neurobiol. 2009;35:189-207 pubmed publisher
    ..This and other studies indicate that CLN3 dysfunction in JNCL may result in multiple disturbances in metabolism that together contribute to the pathophysiological processes underlying this disease. ..
  43. Deniger D, Kolokoltsov A, Moore A, Albrecht T, Davey R. Targeting and penetration of virus receptor bearing cells by nanoparticles coated with envelope proteins of Moloney murine leukemia virus. Nano Lett. 2006;6:2414-21 pubmed
    ..Extrusion provides a rapid, detergent-free method to couple virus membranes to NPs and should be readily applicable for many other virus and NP types. ..
  44. Kakoki M, Kim H, Edgell C, Maeda N, Smithies O, Mattson D. Amino acids as modulators of endothelium-derived nitric oxide. Am J Physiol Renal Physiol. 2006;291:F297-304 pubmed
    ..hy926 endothelial cells. Inhibition of system y(+) or y(+)L by siRNA for the cationic amino acid transporter 1 or the CD98/4F2 heavy chain diminished the NO-depleting effects of these amino acids...
  45. Humphrey B, Klasing K. The acute phase response alters cationic amino acid transporter expression in growing chickens (Gallus gallus domesticus). Comp Biochem Physiol A Mol Integr Physiol. 2005;142:485-94 pubmed
    ..001). The inability of the thymus to compete for lysine and arginine during the APR may limit the ability of thymocytes to develop during infections. ..
  46. Li C, Huang W, Harris M, Goolsby J, Venema R. Interaction of the endothelial nitric oxide synthase with the CAT-1 arginine transporter enhances NO release by a mechanism not involving arginine transport. Biochem J. 2005;386:567-74 pubmed
    ..Taken together, these data suggest that direct interaction of eNOS with CAT-1 enhances NO release by a mechanism not involving arginine transport. ..
  47. Yang S, Huang C, Tsai P, Cheng C, Stevens B, Skimming J. Renal transcription of high-affinity type-2 cationic amino acid transporter is up-regulated in LPS-stimulated rodents. Acta Anaesthesiol Scand. 2004;48:308-16 pubmed
    ..Regulation of L-Arg uptake by modulating the expression regulation of induced CAT-2 and CAT-2B might be a potential target for therapies against renal pathologic conditions related to NO overproduction. ..
  48. Fernandez J, Yaman I, Huang C, Liu H, Lopez A, Komar A, et al. Ribosome stalling regulates IRES-mediated translation in eukaryotes, a parallel to prokaryotic attenuation. Mol Cell. 2005;17:405-16 pubmed
    ..This control is reminiscent of translation attenuation in prokaryotic operons, where inhibition of translation elongation can regulate both mRNA translation and gene transcription by altering mRNA structure. ..
  49. Li J, Wilson A, Gao X, Kuruba R, Liu Y, Poloyac S, et al. Coordinated regulation of dimethylarginine dimethylaminohydrolase-1 and cationic amino acid transporter-1 by farnesoid X receptor in mouse liver and kidney and its implication in the control of blood levels of asymmetric dimethylarginine. J Pharmacol Exp Ther. 2009;331:234-43 pubmed publisher
    ..These data suggest that FXR may play an important role in regulating blood levels of ADMA via coordinated regulation of DDAH-1 and CAT-1 in liver and kidney. ..
  50. Kizhatil K, Albritton L. System y+ localizes to different membrane subdomains in the basolateral plasma membrane of epithelial cells. Am J Physiol Cell Physiol. 2002;283:C1784-94 pubmed
    ..vascular endothelial cells. ..
  51. Kaneko S, Ando A, Okuda Ashitaka E, Maeda M, Furuta K, Suzuki M, et al. Ornithine transport via cationic amino acid transporter-1 is involved in ornithine cytotoxicity in retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2007;48:464-71 pubmed
    ..The results suggest that ornithine transport via CAT-1 may play a crucial role in ornithine cytotoxicity in hTERT-RPE cells. Reduction of the ornithine transport via CAT-1 may be a new target for treatment of gyrate atrophy. ..
  52. Bae E, Park S, Jung Y. Role of a third extracellular domain of an ecotropic receptor in Moloney murine leukemia virus infection. J Microbiol. 2006;44:447-52 pubmed
    The murine ecotropic retroviral receptor has been demonstrated to function as a mouse cationic amino acid transporter 1 (mCAT1), and is comprised of multiple membranespanning domains...
  53. Schwartz I, Grupper A, Soetendorp H, Hillel O, Laron I, Chernichovski T, et al. Attenuated glomerular arginine transport prevents hyperfiltration and induces HIF-1? in the pregnant uremic rat. Am J Physiol Renal Physiol. 2012;303:F396-404 pubmed publisher
    ..These events provoke renal damage manifested by upregulation of renal HIF-1? and loss of the ability to increase glomerular filtration rate during gestation. ..