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.

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 MP037ANTI-APOPTOTIC EFFECT OF GPR40 ACTIVATION IN TNF-ALPHA-INDUCED INJURY OF RAT PROXIMAL TUBULAR CELLS

2017 ◽  
Vol 32 (suppl_3) ◽  
pp. iii440-iii440
Author(s):  
Seong Kwon Ma ◽  
Soo Yeon Joo ◽  
In Jin Kim ◽  
Ha Yeon Kim ◽  
Chang Seong Kim ◽  
...  
Keyword(s):  
Tnf Alpha ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Apoptotic Effect ◽  
Proximal Tubular

Effect of Ifosfamide Metabolites on Sodium-Dependent Phosphate Transport in a Model of Proximal Tubular Cells (LLC-PK1) in Culture

1993 ◽  
Vol 16 (6) ◽  
pp. 285-298 ◽  
Author(s):  
M. Mohrmann ◽  
A. Pauli ◽  
H. Walkenhorst ◽  
B. Schönfeld ◽  
M. Brandis
Keyword(s):  
Phosphate Transport ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Sodium Dependent ◽  
Proximal Tubular

Roles of IL-1 and TNF-alpha in endotoxin-induced activation of nitric oxide synthase in cultured rat brain cells

1996 ◽  
Vol 270 (2) ◽  
pp. R326-R332 ◽  
Author(s):  
L. I. Romero ◽  
J. B. Tatro ◽  
J. A. Field ◽  
S. Reichlin
Keyword(s):  
Nitric Oxide ◽  
Interleukin 1 ◽  
Primary Cultures ◽  
Neonatal Rat ◽  
Tnf Alpha ◽  
Brain Cells ◽  
Nitrite Accumulation ◽  
No Production ◽  
Necrosis Factor Alpha ◽  
Oxide Synthase

In astrocytes and microglia, bacterial lipopolysaccharide (LPS) stimulates production and release of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO). Although IL-1 beta and TNF-alpha are themselves capable of inducing NO synthase (NOS) in glia, the specific factors mediating LPS induction of NOS in brain have not been identified. To determine whether LPS induction of NOS in brain cells is mediated by IL-1 or TNF-alpha, acting alone or in concert, the effects of IL-1-receptor antagonist (IL-1Ra) and of TNF-soluble receptor (TNFsRp55), presented individually and in combination, on LPS-induced NOS activity were tested. In glial-enriched mixed primary cultures of neonatal rat telencephalic cells, LPS (0.1-100 ng/ml), IL-1 beta (0.01-10 nM), and TNF-alpha (0.1-100 nM) each concentration dependently stimulated accumulation of nitrite, an indicator of NO production. Induction of nitrite accumulation by LPS and by IL-1 was blocked by N omega-nitro-L-arginine methyl ester and N omega-monomethyl-L-arginine, indicating that it was mediated by NOS. TNF-alpha alone induced NO production weakly as compared with IL-1, but combined submaximal concentrations of IL-1 beta (1 nM) and TNF-alpha (10 nM) induced NOS synergistically. Furthermore, TNFsRp55 and IL-1Ra each produced a dose-dependent partial inhibition of the NO response to LPS, and the effect of TNFsRp55 was equal to or greater than that of IL-1Ra. TNFsRp55 and IL-1Ra in combination were not significantly more effective than TNF-sRp55 alone. The results indicate that LPS induction of NOS activity in brain cells is mediated in part by both IL-1 beta and TNF-alpha.

Interleukin 1 modulation of renal epithelial glucose and amino acid transport

1988 ◽  
Vol 254 (6) ◽  
pp. F879-F886
Author(s):  
D. E. Kohan ◽  
G. F. Schreiner
Keyword(s):  
Amino Acid ◽  
Amino Acid Transport ◽  
Interleukin 1 ◽  
Peritoneal Macrophages ◽  
Tubular Epithelium ◽  
Acid Transport ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Proximal Tubular Epithelium

We have investigated the effect of immune factors on glucose and amino acid transport by proximal tubular epithelium. Proximal tubular cells were obtained by enzymatic digestion of mouse renal cortex and grown to confluent monolayers. alpha-[14C]methylglucoside (AMG), D-[3H]-aspartate, L-[3H]leucine, and L-[3H]arginine uptake were assayed. Proximal tubular epithelium coincubated with supernatants derived from lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages had a twofold increase in AMG and aspartate uptake that was sodium dependent, was prevented by cycloheximide or actinomycin D, and was not associated with changes in cell growth or differentiation. Chromatographic separation of the macrophage supernatant yielded one fraction, mol wt 16,000-20,000, that enhanced AMG and aspartate uptake and contained interleukin 1 (IL 1) determined by bioassay. Recombinant IL 1 (mol wt 17,500) reproduced changes in AMG and aspartate uptake seen with macrophage supernatants. In contrast, neither macrophage supernatants nor IL 1 affected sodium-independent leucine or arginine transport. IL 1 directly increased 22Na transport into proximal tubular cells. These data indicate that macrophages, via IL 1 secretion, are capable of modulation of sodium-linked solute transport in proximal tubular epithelium.

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.

Regulation of renal sodium-dependent phosphate co-transporter genes (Npt2a and Npt2c) by all-trans-retinoic acid and its receptors

2010 ◽  
Vol 429 (3) ◽  
pp. 583-592 ◽  
Author(s):  
Masashi Masuda ◽  
Hironori Yamamoto ◽  
Mina Kozai ◽  
Sarasa Tanaka ◽  
Mariko Ishiguro ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Sodium Dependent ◽  
Proximal Tubular ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular

The type II sodium-dependent phosphate co-transporters Npt2a and Npt2c play critical roles in the reabsorption of Pi by renal proximal tubular cells. The vitamin A metabolite ATRA (all-trans-retinoic acid) is important for development, cell proliferation and differentiation, and bone formation. It has been reported that ATRA increases the rate of Pi transport in renal proximal tubular cells. However, the molecular mechanism is still unknown. In the present study, we observed the effects of a VAD (vitamin A-deficient) diet on Pi homoeostasis and the expression of Npt2a and Npt2c genes in rat kidney. There was no change in the plasma levels of Pi, but VAD rats significantly increased renal Pi excretion. Renal brush-border membrane Pi uptake activity and renal Npt2a and Npt2c expressions were significantly decreased in VAD rats. The transcriptional activity of a luciferase reporter plasmid containing the promoter region of human Npt2a and Npt2c genes was increased markedly by ATRA and a RAR (retinoic acid receptor)-specific analogue TTNPB {4-[E-2-(5,6,7,8-tetrahydro-5,5,8,8-tetra-methyl-2-naphtalenyl)-1-propenyl] benzoic acid} in renal proximal tubular cells overexpressing RARs and RXRs (retinoid X receptors). Furthermore, we identified RAREs (retinoic acid-response elements) in both gene promoters. Interestingly, the half-site sequences (5′-GGTTCA-3′: −563 to −558) of 2c-RARE1 overlapped the vitamin D-responsive element in the human Npt2c gene and were functionally important motifs for transcriptional regulation of human Npt2c by ATRA and 1,25(OH)2D3 (1α,25-dihydroxyvitamin D3), in both independent or additive actions. In summary, we conclude that VAD induces hyperphosphaturia through the down-regulation of Npt2a and Npt2c gene expression in the kidney.

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