Mineralocorticoid receptor blockade improves arginine transport and nitric oxide generation through modulation of cationic amino acid transporter-1 in endothelial cells

Nitric Oxide ◽  
2018 ◽  
Vol 80 ◽  
pp. 24-31
Author(s):  
Moshe Shashar ◽  
Tamar Hod ◽  
Tamara Chernichovski ◽  
Avital Angel ◽  
Shaul Kazan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Amino Acid ◽  
Mineralocorticoid Receptor ◽  
Amino Acid Transporter ◽  
Receptor Blockade ◽  
Cationic Amino Acid Transporter ◽  
Cationic Amino Acid ◽  
Arginine Transport ◽  
Acid Transporter

Estradiol augments while progesterone inhibits arginine transport in human endothelial cells through modulation of cationic amino acid transporter-1

2015 ◽  
Vol 309 (4) ◽  
pp. R421-R427 ◽  
Author(s):  
Ohad S. Bentur ◽  
Doron Schwartz ◽  
Tamara Chernichovski ◽  
Merav Ingbir ◽  
Talia Weinstein ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Amino Acid ◽  
Protein Content ◽  
Amino Acid Transporter ◽  
Female Rats ◽  
Cationic Amino Acid Transporter ◽  
Cationic Amino Acid ◽  
Arginine Transport ◽  
Arginine Uptake ◽  
Acid Transporter

Decreased generation of nitric oxide (NO) by endothelial NO synthase (eNOS) characterizes endothelial dysfunction (ECD). Delivery of arginine to eNOS by cationic amino acid transporter-1 (CAT-1) was shown to modulate eNOS activity. We found in female rats, but not in males, that CAT-1 activity is preserved with age and in chronic renal failure, two experimental models of ECD. In contrast, during pregnancy CAT-1 is inhibited. We hypothesize that female sex hormones regulate arginine transport. Arginine uptake in human umbilical vein endothelial cells (HUVEC) was determined following incubation with either 17β-estradiol (E2) or progesterone. Exposure to E2 (50 and 100 nM) for 30 min resulted in a significant increase in arginine transport and reduction in phosphorylated CAT-1 (the inactive form) protein content. This was coupled with a decrease in phosphorylated MAPK/extracellular signal-regulated kinase (ERK) 1/2. Progesterone (1 and 100 pM for 30 min) attenuated arginine uptake and increased phosphorylated CAT-1, phosphorylated protein kinase Cα (PKCα), and phosphorylated ERK1/2 protein content. GO-6976 (PKCα inhibitor) prevented the progesterone-induced decrease in arginine transport. Coincubation with both progesterone and estrogen for 30 min resulted in attenuated arginine transport. While estradiol increases arginine transport and CAT-1 activity through modulation of constitutive signaling transduction pathways involving ERK, progesterone inhibits arginine transport and CAT-1 via both PKCα and ERK1/2 phosphorylation, an effect that predominates over estradiol.

scholarly journals Transport of extracellular l-arginine via cationic amino acid transporter is required during in vivo endothelial nitric oxide production

2005 ◽  
Vol 289 (4) ◽  
pp. H1381-H1390 ◽  
Author(s):  
Brett G. Zani ◽  
H. Glenn Bohlen
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Blood Flow ◽  
Amino Acid ◽  
Amino Acid Transporter ◽  
Cationic Amino Acid Transporter ◽  
Cationic Amino Acid ◽  
Arginine Transport ◽  
Endothelial Nitric Oxide

In cultured endothelial cells, 70–95% of extracellular l-arginine uptake has been attributed to the cationic amino acid transporter-1 protein (CAT-1). 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. 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. Our prior studies indicate that each of these perturbations causes NO-dependent vasodilation. The perivascular NO concentration ([NO]) and blood flow were determined in the in vivo rat intestinal microvasculature. Suppression of extracellular l-arginine transport significantly and strongly inhibited increases in vascular [NO] and intestinal blood flow during NaCl hyperosmolarity, lowered oxygen tension, and increased flow. These results suggest that l-arginine from the extracellular space is accumulated by CAT-1. When CAT-1-mediated transport of extracellular l-arginine into endothelial cells was suppressed, the endothelial cell NO response to a wide range of physiological stimuli was strongly depressed.

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

2007 ◽  
Vol 75 (6) ◽  
pp. 2802-2810 ◽  
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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