Cytokine Induced Nitric Oxide Synthesis in Human Proximal Tubular Cells

1994 ◽  
Vol 86 (s30) ◽  
pp. 9P-9P
Author(s):  
G Nicolson ◽  
PK Chaterjee ◽  
A Jardine ◽  
JS McLay
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthesis ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular

Atrial Natriuretic Factor and Angiotensin Ii Stimulate Nitric Oxide Release from Human Proximal Tubular Cells

1995 ◽  
Vol 89 (5) ◽  
pp. 527-531 ◽  
Author(s):  
J. S. McLay ◽  
P. K. Chatterjee ◽  
S. K. Mistry ◽  
R. P. Weerakody ◽  
A. G. Jardine ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Atrial Natriuretic Factor ◽  
Nitric Oxide Production ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Oxide Production ◽  
Natriuretic Factor ◽  
Proximal Tubular ◽  
Atrial Natriuretic

1. It has been recently reported that angiotensin II can enhance atrial natriuretic factor-stimulated cyclic GMP release from brain capillary endothelial cells and stimulate directly the release of cyclic GMP by Neuro 2a cells. A possible mechanism mediating such cyclic GMP release could be via the production of nitric oxide and the resultant stimulation of soluble guanylate cyclase. 2. The ability of angiotensin II, atrial natriuretic factor and c(4–23) atrial natriuretic factor to stimulate nitric oxide production was investigated in primary cultures of human proximal tubular cells. 3. Freshly prepared human proximal tubular cells were seeded onto 6-well plates and allowed to reach confluence. Cells were then incubated with incremental concentrations of either angiotensin II, atrial natriuretic factor or c(4–23) atrial natriuretic factor alone for 1, 4, 12 or 24 h or in the presence of the nitric oxide synthase inhibitor NG-monomethyl-l-arginine. Angiotensin II was also incubated with human proximal tubular cells in the presence of the AT, and AT2 receptor antagonists DuP 753 and PD 123319. 4. Incubation of human proximal tubular cells with angiotensin II, atrial natriuretic factor or c(4–23) atrial natriuretic factor produced a dose- and time-dependent increase in nitric oxide production, which was inhibited in the presence of NG-monomethyl-l-arginine. A similar increase in nitric oxide production was observed after incubation with atrial natriuretic factor or c(4–23) atrial natriuretic factor. 5. The angiotensin-induced increase in nitric oxide production was not inhibited in the presence of either the angiotensin AT1 or AT2 receptor antagonists DuP 753 or PD 123319. 6. This study demonstrates that primary cultures of human proximal tubular cells can be stimulated to produce nitric oxide by both atrial natriuretic factor and angiotensin II. Furthermore, the atrial natriuretic factor-induced response appears to be mediated via the atrial natriuretic factor-C receptor, while the angiotensin II-induced response appears to be mediated by a novel, as yet unidentified, angiotensin II receptor.

scholarly journals Angiotensin II inhibits inducible nitric oxide synthase in tubular MCT cells by a posttranscriptional mechanism.

1997 ◽  
Vol 8 (4) ◽  
pp. 551-557 ◽  
Author(s):  
G Wolf ◽  
F N Ziyadeh ◽  
R Schroeder ◽  
R A Stahl
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Nitric Oxide Synthase ◽  
Ang Ii ◽  
Proximal Tubular Cells ◽  
Inos Protein ◽  
Tubular Cells ◽  
Inos Protein Expression ◽  
Proximal Tubular ◽  
Oxide Synthase

Expression of the inducible isoform of nitric oxide synthase (iNOS) and generation of nitric oxide (NO) have been recently described, in addition to mesangial and medullary thick ascending limb cells, in proximal tubular cells, including MCT, a mouse proximal tubular epithelium cell line. Because vasoconstrictors may interfere with the induction of iNOS and the subsequent generation of NO, in the study presented here, whether exogenous angiotensin II (ANG II) influences bacterial lipopolysaccharide (LPS)/gamma-interferon (gamma-IF)-stimulated NO synthesis and iNOS protein and mRNA expression in MCT cells was tested. LPS/gamma-IF readily stimulated nitrite synthesis in MCT cells, as one measured parameter of NO synthesis. Coincubation of cells with 10(-9)-10(-6) M ANG II attenuated this LPS/gamma-IF-stimulated induction of nitrite. This effect was reversed by the AT1-receptor blocker losartan, but not by an AT2-receptor antagonist, indicating signal transduction through AT1-receptors. Western blot analysis applying a specific monoclonal antibody generated against mouse iNOS revealed that 10(-8)-10(-6) M ANG II significantly reduced LPS/gamma-IF-induced iNOS protein expression. However, ANG II had no effect on LPS/gamma-IF-induced iNOS mRNA as assessed by Northern blots. Moreover, transient transfection studies using a chimeric gene construct, in which iNOS regulatory elements are linked to the CAT reporter gene, showed no effect of ANG II on the LPS/gamma-IF-stimulated transcriptional activity. The study presented here demonstrates that ANG II influences LPS/gamma-IF-stimulated NO generation in MCT cells, most likely at a posttranscriptional level, by influencing iNOS protein expression. Whether proximal tubular cells in vivo express iNOS remains to be established, but this study suggests a mechanism for how iNOS activity is influenced by ANG II in cultured proximal tubular cells.

scholarly journals Association of nitric oxide production by kidney proximal tubular cells in response to lipopolysaccharide and cytokines with cellular damage.

1997 ◽  
Vol 41 (3) ◽  
pp. 557-562 ◽  
Author(s):  
A F Kaboré ◽  
M Denis ◽  
M G Bergeron
Keyword(s):  
Nitric Oxide ◽  
Interleukin 1 ◽  
Cellular Damage ◽  
Tnf Alpha ◽  
No Production ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Sodium Dependent ◽  
Proximal Tubular ◽  
Nitrate And Nitrite

Recent findings suggest that nitric oxide (NO) is an important biologic mediator which exerts a wide variety of effects on numerous physiological and pathophysiological processes. L-Arginine is oxidized to L-citrulline with concomitant NO production; as a result, nitrate and nitrite accumulates. This study was conducted to determine the potential NO production by proximal tubular cells (PTC) in response to bacterial lipopolysac-charides (LPS) and cytokines and to evaluate the cytotoxic effect associated with NO release. After a 7-day stimulation with LPS (100 micrograms/ml), interleukin-1 beta (IL-1 beta) (10 ng/ml), and tumor necrosis factor alpha (TNF-alpha) (10 ng/ml), the nitrate and nitrite levels were determined by a spectrophotometric method based on the Griess reaction. Moreover, alpha-methylglucopyranoside phosphate and lactate dehydrogenase release and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay served as indicators of sodium-dependent hexose transport integrity and cell death, respectively. IL-1 beta and TNF-alpha used alone or together or combined with LPS led to a significant generation of NO by PTC. Our results also demonstrate that NO induced by LPS and cytokines could inhibit sodium-dependent transport and could induce PTC damage.

scholarly journals Nitric oxide production by human proximal tubular cells: A novel immunomodulatory mechanism?

1994 ◽  
Vol 46 (4) ◽  
pp. 1043-1049 ◽  
Author(s):  
James S. McLay ◽  
Prabal Chatterjee ◽  
A. Graham Nicolson ◽  
Allan G. Jardine ◽  
Neil G. McKay ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Production ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Oxide Production ◽  
Proximal Tubular

Low-affinity transport of pyroglutamyl-histidine in renal brush-border membrane vesicles

1989 ◽  
Vol 257 (5) ◽  
pp. C971-C975 ◽  
Author(s):  
H. A. Skopicki ◽  
K. Fisher ◽  
D. Zikos ◽  
G. Flouret ◽  
D. R. Peterson
Keyword(s):  
Brush Border ◽  
Brush Border Membrane ◽  
Membrane Vesicles ◽  
Brush Border Membrane Vesicles ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Luminal Membrane ◽  
Renal Brush Border Membrane ◽  
Proximal Tubular ◽  
Renal Brush Border

These studies were performed to determine if a low-affinity carrier is present in the luminal membrane of proximal tubular cells for the transport of the dipeptide, pyroglutamyl-histidine (pGlu-His). We have previously described the existence of a specific, high-affinity, low-capacity [transport constant (Kt) = 9.3 X 10(-8) M, Vmax = 6.1 X 10(-12) mol.mg-1.min-1] carrier for pGlu-His in renal brush-border membrane vesicles. In the present study, we sought to demonstrate that multiple carriers exist for the transport of a single dipeptide by determining whether a low-affinity carrier also exists for the uptake of pGlu-His. Transport of pGlu-His into brush-border membrane vesicles was saturable over the concentration range of 10(-5)-10(-3) M, yielding a Kt of 6.3 X 10(-5) M and a Vmax of 2.2 X 10(-10) mol.mg-1.min-1. Uptake was inhibited by the dipeptides glycyl-proline, glycyl-sarcosine, and carnosine but not by the tripeptide pyroglutamyl-histidyl-prolinamide. We conclude that 1) pGlu-His is transported across the luminal membrane of the proximal tubule by multiple carriers and 2) the lower affinity carrier, unlike the higher affinity carrier, is nonspecific with respect to other dipeptides.

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