Tonoplast-Localized Theanine Transporter CsCAT2 May Mediate Theanine Storage in the Root of Tea Plants (Camellia sinensis L.)

Theanine is the component endowing tea infusion with “umami” taste and antidepression benefits. Theanine is primarily synthesized and stored in root in winter and is transported via vascular tissues to the new shoot in spring. However, the mechanism underlying theanine storage in the root of tea plants remains largely unknown. Cationic amino acid transporter 2 (CsCAT2) in tea plants is homologous to glutamine permease 1 (GNP1), the specific glutamine transporter in yeast. In this study, we identified CsCAT2 as an H+-dependent theanine transporter with medium affinity for theanine. The result of subcellular localization showed that CsCAT2 was a tonoplast-localized transporter. Importantly, CsCAT2 highly expressed in the root in winter during theanine storage and reduced its expression in the root during theanine transport from root-to-shoot in spring. In addition, CsCAT2 expression in the roots of 5 varieties at four time points during December and April was significant negatively correlated with the capacity of theanine root-to-shoot movement. Taken together, these results suggested that CsCAT2 may mediate theanine storage in the vacuole of root cells and may negatively modulate theanine transport from root to shoot.

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Regulation of arginase isoforms I and II by IL-4 in cultured murine peritoneal macrophages

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.276.1.r237 ◽

1999 ◽

Vol 276 (1) ◽

pp. R237-R242 ◽

Cited By ~ 15

Author(s):

Claudine A. Louis ◽

Vino Mody ◽

William L. Henry ◽

Jonathan S. Reichner ◽

Jorge E. Albina

Keyword(s):

Amino Acid ◽

Subcellular Localization ◽

Peritoneal Macrophages ◽

Cationic Amino Acid Transporter ◽

Cationic Amino Acid ◽

Th2 Cytokine ◽

Enhanced Expression ◽

Murine Peritoneal Macrophages ◽

Differential Induction ◽

Arginine Concentration

Macrophages can express two arginase isoforms with distinct subcellular localization (cytosolic AI and mitochondrial AII). These isoforms are products of different genes and are capable of differential induction. Experiments were performed to identify the specific arginase isoforms induced by interleukin (IL)-4, a Th2 cytokine shown by others to increase arginase activity in macrophages, and serum. Results indicate IL-4, in concert with serum, increases AI, but not AII, mRNA in cultured murine macrophages. Moreover, they show serum to induce both arginase isoforms and to be required for maximal AI induction by IL-4. Together with the enhanced expression of AI, IL-4 induced the expression of the cationic amino acid transporter MCAT-2 and increasedl-arginine transport into the cells. Present results confirm, then, specificity in the ability of macrophage arginase isoforms to be induced by different stimuli. Moreover, they suggest that a decrease in intracellularl-arginine concentration resulting from its consumption by arginase may be repaired by concurrent increases inl-arginine influx into the cell.

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l-Arginine and Cationic Amino Acid Transporter 2B Regulate Growth and Survival of Leishmania amazonensis Amastigotes in Macrophages

Infection and Immunity ◽

10.1128/iai.00026-07 ◽

2007 ◽

Vol 75 (6) ◽

pp. 2802-2810 ◽

Cited By ~ 44

Author(s):

Nanchaya Wanasen ◽

Carol L. MacLeod ◽

Lesley G. Ellies ◽

Lynn Soong

Keyword(s):

Amino Acid ◽

Amino Acid Transporter ◽

Parasite Growth ◽

Leishmania Amazonensis ◽

Growth Enhancement ◽

Cationic Amino Acid Transporter ◽

Cationic Amino Acid ◽

Arginine Transport ◽

Ifn Γ ◽

Acid Transporter

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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Cationic Amino Acid Transporter-1 (CAT-1) Promotes Fibroblast-Like Synoviocytes Proliferation and Cytokine Secretion by Taking Up L-Arginine in Rheumatoid Arthritis

10.21203/rs.3.rs-1147918/v1 ◽

2021 ◽

Author(s):

Ying Lu ◽

Chongbo Hao ◽

Shanshan Yu ◽

Zuan Ma ◽

Xuelian Fu ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Amino Acid ◽

Synovial Fluid ◽

Culture Conditions ◽

Cytokine Secretion ◽

Cationic Amino Acid Transporter ◽

Cationic Amino Acid ◽

The Relationship ◽

Fibroblast Like Synoviocytes

Abstract Background: Abnormal proliferation of fibroblast-like synoviocytes (FLSs) in the synovial lining layer is the primary cause of synovial hyperplasia and joint destruction in rheumatoid arthritis (RA). Currently, the relationship between metabolic abnormalities and FLS proliferation is a new focus of investigation. However, little is known regarding the relationship between amino acid metabolism and RA. Methods: The concentrations of amino acids and cytokines in the synovial fluid of RA (n=9) and osteoarthritis (OA,n=9) were detected by LC-MS/MS and CBA assay, respectively. The mRNA and protein expression of CAT-1 were determined in FLSs isolated from RA and OA patients by real-time PCR and western blotting. MTT assay, cell cycle, apoptosis, invasion and cytokine secretion were determined in FLSs knocked down of CAT-1 using siRNA or treated with D-arginine under normoxic and hypoxic culture conditions. A mouse collagen-induced arthritis (CIA) model was applied to test the therapeutic potential of blocking the uptake of L-arginine in vivo.Results: L-arginine was upregulated in the synovial fluid of RA patients and was positively correlated with elevation of the cytokines IL-1β, IL-6 and IL-8. Further examination demonstrated that cationic amino acid transporter-1 (CAT-1) was the primary transporter for L-arginine and was overexpressed on RA FLSs compared to OA FLSs. Moreover, knockdown of CAT-1 using siRNA or inhibition of L-arginine uptake using D-arginine significantly suppressed L-arginine metabolism, cell proliferation, migration and cytokine secretion in RA FLSs under normoxic and hypoxic culture conditions in vitro but increased cell apoptosis in a dose-dependent manner. Meanwhile, in vivo assays revealed that an L-arginine-free diet or blocking the uptake of L-arginine using D-arginine suppressed arthritis progression in CIA mice. Conclusion: CAT-1 is upregulated and promotes FLS proliferation by taking up L-arginine, thereby promoting RA progression.

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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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Molecular Identification and Characterization of Hydroxycinnamoyl Transferase in Tea Plants (Camellia sinensis L.)

International Journal of Molecular Sciences ◽

10.3390/ijms19123938 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3938 ◽

Cited By ~ 2

Author(s):

Chi-Hui Sun ◽

Chin-Ying Yang ◽

Jason Tzen

Keyword(s):

Abiotic Stress ◽

Amino Acid ◽

Camellia Sinensis ◽

Polymerase Chain Reaction Analysis ◽

Coffea Canephora ◽

Tea Plant ◽

Amino Acid Sequences ◽

Hibiscus Cannabinus ◽

Expression Level ◽

Tea Plants

Tea (Camellia sinensis L.) contains abundant secondary metabolites, which are regulated by numerous enzymes. Hydroxycinnamoyl transferase (HCT) is involved in the biosynthesis pathways of polyphenols and flavonoids, and it can catalyze the transfer of hydroxyconnamoyl coenzyme A to substrates such as quinate, flavanol glycoside, or anthocyanins, thus resulting in the production of chlorogenic acid or acylated flavonol glycoside. In this study, the CsHCT gene was cloned from the Chin-Shin Oolong tea plant, and its protein functions and characteristics were analyzed. The full-length cDNA of CsHCT contains 1311 base pairs and encodes 436 amino acid sequences. Amino acid sequence was highly conserved with other HCTs from Arabidopsis thaliana, Populus trichocarpa, Hibiscus cannabinus, and Coffea canephora. Quantitative real-time polymerase chain reaction analysis showed that CsHCT is highly expressed in the stem tissues of both tea plants and seedlings. The CsHCT expression level was relatively high at high altitudes. The abiotic stress experiment suggested that low temperature, drought, and high salinity induced CsHCT transcription. Furthermore, the results of hormone treatments indicated that abscisic acid (ABA) induced a considerable increase in the CsHCT expression level. This may be attributed to CsHCT involvement in abiotic stress and ABA signaling pathways.

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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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