Cationic Amino Acid Transporter 2

ABSTRACT Leishmania spp. are obligate intracellular parasites, requiring a suitable microenvironment for their growth within host cells. We previously reported that the growth of Leishmania amazonensis amastigotes in murine macrophages (Mφs) was enhanced in the presence of gamma interferon (IFN-γ), a Th1 cytokine normally associated with classical Mφ activation and killing of intracellular pathogens. In this study, we provided several lines of evidence suggesting that IFN-γ-mediated parasite growth enhancement was associated with l-arginine transport via mouse cationic amino acid transporter 2B (mCAT-2B). (i) mRNA expression of Slc7A2, the gene encoding for mCAT-2B, as well as l-arginine transport was increased in IFN-γ-treated Mφs. (ii) Supplementation of l-arginine in Mφ cultures increased parasite growth. (iii) Parasite growth enhancement in wild-type Mφs was inhibited in the presence of nonmetabolized l-arginine analogues. (iv) IFN-γ-mediated parasite growth was absent in Mφs derived from mCAT-2B-deficient mice. Although we detected a clear upregulation of mCAT-2B and l-arginine transport, no measurable iNOS or arginase activities were observed in IFN-γ-treated, infected Mφs. Together, these data suggest an involvement of a novel l-arginine usage independent of iNOS and arginase activities during IFN-γ-mediated parasite growth enhancement. A possible role of mCAT-2B in supplying l-arginine directly to the parasites for their proliferation is discussed.

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Stress differentially induces cationic amino acid transporter gene expression

Biochimica et Biophysica Acta (BBA) - Biomembranes ◽

10.1016/s0005-2736(98)00155-2 ◽

1998 ◽

Vol 1414 (1-2) ◽

pp. 75-84 ◽

Cited By ~ 39

Author(s):

Donald K. Kakuda ◽

Kim D. Finley ◽

Michio Maruyama ◽

Carol L. MacLeod

Keyword(s):

Gene Expression ◽

Amino Acid ◽

Amino Acid Transporter ◽

Cationic Amino Acid Transporter ◽

Transporter Gene ◽

Cationic Amino Acid ◽

Acid Transporter ◽

Amino Acid Transporter Gene

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Circular RNA NF1-419 Inhibits Proliferation and Induces Apoptosis by Regulating Lipid Metabolism in Astroglioma Cells

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892816666210729125802 ◽

2021 ◽

Vol 16 ◽

Author(s):

Ran Li ◽

Xiaocui Tang ◽

Changqiong Xu ◽

Yinrui Guo ◽

Longkai Qi ◽

...

Keyword(s):

Lipid Metabolism ◽

Amino Acid ◽

Tumor Growth ◽

Ganoderma Lucidum ◽

Amino Acid Transporter ◽

Cationic Amino Acid Transporter ◽

Cationic Amino Acid ◽

Acid Transporter ◽

Astroglioma Cells

Background: Astroglioma is the most common primary tumor of the central nervous system. Currently, there is no effective treatment for astroglioma. In the present study, the extract (L3) from Ganoderma Lucidum (G.lucidum) was found to inhibit the growth of astroglioma U87 cells and change the expression of circular RNAs (circRNAs). One of these, including the circular NF1-419 (circNF1-419), was of interest because NF1 gene is a classic tumor suppressor gene. Objective: The functional role of circ-NF1-419 in the inhibition of astroglioma cells remains unknown. This study focuses on the role of circNF1-419 in functional abnormalities of U87 astroglioma cells and aims to elaborate on its regulatory mechanism. Methods: The circNF1-419 overexpressing U87 (U87-NF1-419) cells were constructed. We generated U87-NF1-419 to evaluate the role of circNF1-419 on cell cycle, apoptosis, proliferation, tumor growth and metabolic regulation. Finally, we used docking screening to identify compounds in G. lucidum extracts that target circ-419. Results: U87-NF1-419 can promote cell apoptosis and regulate lipid metabolism through glycerophospholipid metabolism and retrograde endocannabinoid signaling. Further examinations revealed that the expression of metabolic regulators, such as L-type voltage-operated calcium channels (L-VOCC), phospholipase C-β3 (PLCβ3), Mucin1, cationic amino acid transporter 4 (CAT4), cationic amino acid transporter 1 (CAT1) and a kinase (PRKA) anchor protein 4 (AKAP4) was inhibited, while phosphatidylserine synthase 1 (PTDSS1) was enhanced in U87-NF1-419 cells. In vivo experiments showed that circNF1-419 inhibits tumor growth in BALB/C nude mice, and enhanced AKAP4 and PTDSS1 in tumor tissues. The virtual docking screening results supported that ganosporeric acid A, ganodermatriol, ganoderic acid B and α-D-Arabinofuranosyladenine in L3 could activate circNF1-419 in astroglioma treatment. Conclusion: This study indicated that circNF1-419 could be a therapeutic target for the clinical treatment of astroglioma. L3 from Ganoderma Lucidum (G.lucidum) could inhibit astroglioma growth by activating circNF1-419.

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Galectin-lattice sustains function of cationic amino acid transporter and insulin secretion of pancreatic β cells

The Journal of Biochemistry ◽

10.1093/jb/mvaa007 ◽

2020 ◽

Vol 167 (6) ◽

pp. 587-596 ◽

Cited By ~ 1

Author(s):

Kento Maeda ◽

Masayoshi Tasaki ◽

Yukio Ando ◽

Kazuaki Ohtsubo

Keyword(s):

Insulin Secretion ◽

Amino Acid ◽

Cell Surface ◽

Amino Acid Transporter ◽

Cell Surface Expression ◽

Cationic Amino Acid Transporter ◽

Β Cells ◽

Pancreatic Β Cells ◽

Cationic Amino Acid ◽

Acid Transporter

Abstract Maintenance of cell surface residency and function of glycoproteins by lectins are essential for regulating cellular functions. Galectins are β-galactoside-binding lectins and form a galectin-lattice, which regulates stability, clustering, membrane sub-domain localization and endocytosis of plasmalemmal glycoproteins. We have previously reported that galectin-2 (Gal-2) forms a complex with cationic amino acid transporter 3 (CAT3) in pancreatic β cells, although the biological significance of the molecular interaction between Gal-2 and CAT3 has not been elucidated. In this study, we demonstrated that the structure of N-glycan of CAT3 was either tetra- or tri-antennary branch structure carrying β-galactosides, which works as galectin-ligands. Indeed, CAT3 bound to Gal-2 using β-galactoside epitope. Moreover, the disruption of the glycan-mediated bindings between galectins and CAT3 significantly reduced cell surface expression levels of CAT3. The reduced cell surface residency of CAT3 attenuated the cellular arginine uptake activities and subsequently reduced nitric oxide production, and thus impaired the arginine-stimulated insulin secretion of pancreatic β cells. These results indicate that galectin-lattice stabilizes CAT3 by preventing endocytosis to sustain the arginine-stimulated insulin secretion of pancreatic β cells. This provides a novel cell biological insight into the endocrinological mechanism of nutrition metabolism and homeostasis.

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The cationic amino acid exporter Slc7a7 is induced and vital in zebrafish tissue macrophages with sustained efferocytic activity

Journal of Cell Science ◽

10.1242/jcs.249037 ◽

2020 ◽

Vol 133 (20) ◽

pp. jcs249037

Author(s):

Doris Lou Demy ◽

Mireille Carrère ◽

Ramil Noche ◽

Muriel Tauzin ◽

Marion Le Bris ◽

...

Keyword(s):

Cell Death ◽

Amino Acid ◽

Neuronal Apoptosis ◽

Amino Acid Transporter ◽

Cationic Amino Acid Transporter ◽

Adaptive Responses ◽

Functional Link ◽

Cationic Amino Acid ◽

Zebrafish Larvae ◽

Acid Transporter

ABSTRACTMost tissues harbor a substantial population of resident macrophages. Here, we elucidate a functional link between the Slc7a7 cationic amino acid transporter and tissue macrophages. We identified a mutant zebrafish devoid of microglia due to a mutation in the slc7a7 gene. We found that in Slc7a7-deficient larvae, macrophages do enter the retina and brain to become microglia, but then die during the developmental wave of neuronal apoptosis, which triggers intense efferocytic work from them. A similar macrophage demise occurs in other tissues, at stages where macrophages have to engulf many cell corpses, whether due to developmental or experimentally triggered cell death. We found that Slc7a7 is the main cationic amino acid transporter expressed in macrophages of zebrafish larvae, and that its expression is induced in tissue macrophages within 1–2 h upon efferocytosis. Our data indicate that Slc7a7 is vital not only for microglia but also for any steadily efferocytic tissue macrophages, and that slc7a7 gene induction is one of the adaptive responses that allow them to cope with the catabolism of numerous dead cells without compromising their own viability.

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