Disease relevance of Slc7a1

• Cat-1 is a protein with a dual function, a high affinity, low capacity cationic amino acid transporter of the y+ system and the receptor for the ecotropic retrovirus [1].
• The regulation of the high affinity cationic amino acid transporter Cat-1 in Fao rat hepatoma cells by amino acid availability has been studied [2].
• The cell surface receptor for ecotropic host-range (infection limited to mice or rats) murine leukemia viruses (MuLVs) is the widely expressed system y+ transporter for cationic amino acids (CAT-1) [3].
• Hypothermia attenuates iNOS, CAT-1, CAT-2, and nitric oxide expression in lungs of endotoxemic rats [4].
• Pulmonary transcription of CAT-2 and CAT-2B but not CAT-1 and CAT-2A were upregulated in hemorrhagic shock rats [5].

High impact information on Slc7a1

• Cat-1, the transporter for the essential amino acids, arginine and lysine, is one of the up-regulated genes [6].
• It is shown here that cat-1 gene expression is also induced by Glc limitation, which causes a 7-fold increase in cat-1 mRNA, a 30-fold induction of Cat-1 protein levels, and a 4-fold stimulation of arginine uptake [7].
• These results strongly suggest that peroxynitrite-mediated activation of the Cat1 transporter in glial cells may serve as a mechanism focused to replenish L-arginine in the neighboring neurons [8].
• Endogenous production of peroxynitrite in lipopolysaccharide-treated astrocytes triggered an increased L-arginine transport activity without affecting Cat1 l-arginine transporter mRNA levels [8].
• Furthermore, peroxynitrite stimulation of L-arginine release was abolished in fibroblast cells homozygous for a targeted inactivation of the Cat1 gene [8].

Chemical compound and disease context of Slc7a1

• In FTO2B rat hepatoma cells, expression of the gene is constitutive and accumulation of Cat-1 mRNAs in response to dexamethasone and insulin was dependent on transcription and protein synthesis [9].

Biological context of Slc7a1

• We have suggested that Cat-1 is required in the regenerating liver for the transport of cationic amino acids and polyamines in the late G1 phase, a process that is essential for liver cells to enter mitosis [1].
• This is the first example of mammalian regulation of internal ribosomal entry sequence-mediated translation by eIF2alpha phosphorylation during amino acid starvation, suggesting that the mechanism of induced Cat-1 protein synthesis is part of the adaptive response of cells to amino acid limitation [10].
• 4F2hc-injected oocytes accumulated substrates to a level higher than CAT1-injected oocytes (i.e. oocytes expressing system y+) and showed exchange of amino acids with the substrate specificity of system y+L and L-leucine-induced outward currents in the absence of extracellular sodium [11].
• This time course of infection paralleled expression of the gene for the Ecor, which was rapidly induced between 2 and 6 h during liver regeneration [12].
• The DeltaAd5/11 vector used to express ecoR allowed for expansion of retrovirally transduced cells, whereas transduction with the first-generation Ad5/11 vector resulted in cytotoxicity and, over time, loss of cells expressing the retrovirus-vector-derived transgene [13].

Anatomical context of Slc7a1

• We tested the hypothesis that extracellular l-arginine entry into endothelial cells via CAT-1 plays a crucial role in endothelial nitric oxide (NO) production during in vivo conditions [14].
• To assess whether this property of the XC cell line arises from differences in its ecotropic MLV receptor, CAT1, we isolated CAT1 cDNA clones from XC cells [15].
• These results suggest that l-arginine from the extracellular space is accumulated by CAT-1 [14].
• Cytokines and insulin induce cationic amino acid transporter (CAT) expression in cardiac myocytes. Regulation of L-arginine transport and no production by CAT-1, CAT-2A, and CAT-2B [16].
• Constitutive CAT-1 mRNA was weakly present in neurons and astrocytes, was not inducible in either cell type, and contributed <3% to total System y+ activity [17].

Associations of Slc7a1 with chemical compounds

• Using l-lysine, the preferred amino acid transported by CAT-1, we competitively inhibited extracellular l-arginine transport into endothelial cells during conditions of NaCl hyperosmolarity, low oxygen, and flow increase [14].
• However, Western blot analyses of peroxynitrite-treated astrocytes and C6 glial cells revealed a 3-nitrotyrosinated anti-Cat1-immunopositive band, strongly suggesting peroxynitrite-mediated Cat1 nitration [8].
• The capacity of PDGF to up-regulate the transport of L-ornithine by inducing the expression of the genes for CAT-1 and CAT-2B may modulate its mitogenic effect by providing SMC with the necessary intracellular precursor for polyamine biosynthesis [18].
• Allicin had no effect on steady-state CAT-1 mRNA levels [19].
• Groups (n = 6-10) of anesthetized SHRs received graded intravenous doses of Ns: tempol (T), 4-amino-tempo (AT), 4-oxo-tempo (OT), 4-trimethylammonium-2,2,6,6-tetramethylpiperidine-1-oxyl iodide (CAT-1), 3-carbamoyl-proxyl (3-CP), or 3-carboxy-proxyl (3-CTPY) [20].

Other interactions of Slc7a1

• Although the 4-5 S ER receptor concentrations remained low, both progesterone receptor forms appeared to recover by 60 days after treatment [21].
• These findings suggest that together CAT-1 and CAT-2B play an important role in providing substrate for high-output NO synthesis in vitro as well as in vivo and implicate a coordinated regulation of intracellular iNOS enzyme activity with membrane arginine transport [22].
• 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 [23].
• In conclusion, our results suggest that RASMCs constitutively express transcripts for CAT-1, CAT-2A and CAT-2B, and that expression of these transcripts is significantly enhanced by LPS and IFN-gamma [24].

Analytical, diagnostic and therapeutic context of Slc7a1

• Reverse transcriptase-polymerase chain reaction detected the presence of mRNA encoding two distinct cationic amino acid transporter (CAT) proteins, CAT-1 and CAT-2B [18].
• Using reverse transcriptase-polymerase chain reaction and Northern blotting, we found a significant increase in glomerular and aortic CAT-1 mRNA expression in CRF [25].
• Immunoblotting experiments demonstrated that CAT1 immunoreactive protein was significantly decreased by approximately 30% in rats maintained on a high-NaCl diet (n = 5) compared with rats on a low-NaCl diet (n = 5) [26].
• Hemorrhage and/or resuscitation, however, did not affect the expression of pulmonary CAT-1 and CAT-2A [5].

References