Abstract:
:Treatment of mesangial cells with recombinant human interleukin 1 beta (IL-1 beta) triggers the expression of a macrophage-type of nitric oxide (NO) synthase and the subsequent increase of cellular concentration of cGMP and nitrite production. Tetrahydrobiopterin (BH4) is an essential cofactor for NO synthase, and in the present study we investigated its impact on inducible NO synthesis in mesangial cells. Inhibition of GTP-cyclohydrolase I, the rate-limiting enzyme for BH4 synthesis, with 2,4-diamino-6-hydroxy-pyrimidine (DAHP) potently suppresses IL-1 beta-induced nitrite production and elevation of cellular cGMP levels. This inhibitory effect of DAHP is reversed by sepiapterin, which provides BH4 via the pterin salvage pathway. Most importantly, sepiapterin dose-dependently augments IL-1 beta-stimulated NO synthesis, indicating that the availability of BH4 limits the production of NO in cytokine-induced mesangial cells. N-acetylserotonin, an inhibitor of the BH4 synthetic enzyme sepiapterin reductase, completely abolishes IL-1 beta-stimulated nitrite production, whereas methotrexate, which inhibits the pterin salvage pathway, displays only a moderate inhibitory effect, thus suggesting that mesangial cells predominantly synthesize BH4 by de novo synthesis from GTP. In conclusion, these data demonstrate that BH4 synthesis is an absolute requirement for, and limits IL-1 beta induction of NO synthesis in mesangial cells. Inhibition of BH4 synthesis may provide new therapeutic approaches to the treatment of pathological conditions involving increased NO formation.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Mühl H,Pfeilschifter Jdoi
10.1038/ki.1994.398subject
Has Abstractpub_date
1994-11-01 00:00:00pages
1302-6issue
5eissn
0085-2538issn
1523-1755pii
S0085-2538(15)58679-1journal_volume
46pub_type
杂志文章abstract:BACKGROUND:Renal salt wasting and hypotension are some of the frequent complications in patients treated with cis-diamminedichloroplatinum (II) (cDDP), and it is suggested that cDDP produces an abnormality in the renin-angiotensin system. However, not only the underlying mechanism but also prophylactic treatment of thi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00307.x
更新日期:2000-10-01 00:00:00
abstract::Increasing evidence points to the importance of aberrant O-glycosylated immunoglobulin A1 (IgA1) in the pathogenesis of IgA nephropathy (IgAN), a disease widely considered to be a polygenic disorder. We earlier found that haplotypes in two key glycosyltransferase genes, C1GALT1 and ST6GALNAC2, were associated with sus...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.99
更新日期:2009-07-01 00:00:00
abstract::Urinary proteomics is a promising tool for biomarker investigation, particularly in complex kidney diseases. Fabris and colleagues report that urinary laminin subunit alpha-2 is a potential diagnostic marker of medullary sponge kidney (MSK) disease by using a label-free quantitative proteomics platform and a clinicall...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.10.032
更新日期:2017-02-01 00:00:00
abstract::Recent studies have shown renoprotective effects of the peroxisome proliferator-activated receptor-α (PPAR-α), but its role in kidney fibrosis is unknown. In order to gain insight into this, we examined the effect of a novel PPAR-α agonist, BAY PP1, in two rat models of renal fibrosis: unilateral ureteral obstruction ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.254
更新日期:2011-12-01 00:00:00
abstract::Peptides representing potential antigenic regions of the NC-1 and 7-S domains of the human alpha 1 and alpha 2, and bovine alpha 3 chains of type IV collagen were synthesized either chemically or by the recombinant DNA technique and tested by ELISA using antibodies raised in rabbits against the whole type IV collagen ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.16
更新日期:1993-01-01 00:00:00
abstract::To determine the effect of an acute load of potassium on potassium reabsorption by the loop of Henle in chronic renal failure, the right kidney was removed and branches of the left renal artery were ligated in 17 rats. One week later and after 2 days of a potassium-free diet, rats were studied before (period 1) and af...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1985.100
更新日期:1985-06-01 00:00:00
abstract::Human transitional B cells express relatively high IL-10 and low TNF-α levels, which correlate with B regulatory activity in vitro. Herein, we aim to further define B regulatory phenotype and determine whether B regulatory activity can serve as a prognostic marker for renal allograft dysfunction (graft loss or 2-fold ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.08.028
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Disorders that manifest hypokalemic metabolic alkalosis, such as Bartter's syndrome and Gitelman's syndrome, are caused by the malfunction of renal tubular electrolyte transporters. Bartter's syndrome may be linked to dysfunction of Na-K-2Cl cotransporter (NKCC2), renal outer medullary K channel (ROMK), or C...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00163.x
更新日期:2003-09-01 00:00:00
abstract::The genomic action of calcitriol is mediated through the interaction of the calcitriol receptor (VDR) with vitamin D response elements (VDREs) of the target genes. We have shown that the interaction of VDRs with VDREs is inhibited by uremic toxins. We hypothesize that uremic toxins form Schiff bases with the lysine re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.469
更新日期:1996-11-01 00:00:00
abstract:BACKGROUND:The induction of stress response (heat shock) proteins (HSPs) is a highly conserved response that protects many cell types from diverse physiological and environmental stressors. We tested the hypothesis that the induction of HSPs is protective in experimental renal ischemia/reperfusion injury. METHODS:The ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0590051798.x
更新日期:2001-05-01 00:00:00
abstract::Loss of hypoxic vasodilation has been proposed as a causative factor in the development of hypertension in dialysis patients treated with recombinant human erythropoietin (rHuEPO). Venous occlusion plethysmography was therefore performed on 22 dialysis patients (aged 23 to 71 years, dialysis duration 6 to 260 months, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.376
更新日期:1992-10-01 00:00:00
abstract::Tissandié and colleagues report in this issue on their studies of IgA1 glycosylation and biological activities of IgA1-containing circulating immune complexes in patients with alcoholic cirrhosis who developed secondary renal disease with IgA deposits, secondary IgA nephropathy. Their seminal findings demonstrate abno...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2011.302
更新日期:2011-12-01 00:00:00
abstract::Low density lipoprotein (LDL) deposition and local oxidation play a key role in the pathogenesis of atherosclerosis and may likewise contribute to glomerular injury. These studies were designed to determine whether cultured human mesangial cells oxidize homologous LDL and to compare the effects of unmodified and oxidi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.214
更新日期:1994-06-01 00:00:00
abstract:BACKGROUND:Pre-eclampsia is characterized by hypertension, proteinuria and edema. Simultaneous studies of kidney function and structure have not been reported. We wished to explore the degree and nature of glomerular dysfunction in pre-eclampsia. METHODS:Physiologic techniques were used to estimate glomerular filtrati...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00097.x
更新日期:1998-10-01 00:00:00
abstract:BACKGROUND:The superiority of renin-angiotensin system (RAS) blockade in providing renoprotection has been attributed to class-specific blood pressure "(BP)-independent" mechanisms. However, the conventional BP measurement methodology on which such conclusions are based is inherently limited for an accurate assessment ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00009.x
更新日期:2000-04-01 00:00:00
abstract::Continuous antigen stimulation during chronic infection or malignancy can promote functional T cell silencing, a phenomenon called T cell exhaustion. The prevalence and impact of T cell exhaustion following organ transplantation, another immune stimulus with persistently high antigen load, are unknown. Here, we charac...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2019.01.040
更新日期:2019-08-01 00:00:00
abstract::Albumin is an acceptor of lysophosphatidylcholine (LPC), product of the lecithin:cholesterol acyl transferase (LCAT) reaction, and it has been suggested that low LCAT activity and reduced cholesterol esterification rate in patients with the nephrotic syndrome may be linked to depletion of albumin. Effects of low plasm...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.248
更新日期:1994-07-01 00:00:00
abstract::Migration of monocytes into the vessel wall contributes to the onset and progression of atherosclerosis. Because monocytes are a heterogeneous population, we determined potential associations between monocyte subsets and cardiovascular events in a prospective cohort of 94 dialysis patients followed for 35 months. The ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002744
更新日期:2008-03-01 00:00:00
abstract::Meprins are zinc-dependent metalloproteinases that are highly expressed in the brush-border membranes of both the kidney and the intestines. Meprins are capable of proteolytically degrading extracellular matrix proteins, proteolytically processing bioactive proteins, and play a role in inflammatory processes. In this ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002189
更新日期:2007-05-01 00:00:00
abstract:BACKGROUND:While an understanding of the epidemiology and clinical course of HIV-associated nephropathy (HIVAN) is growing, little is known about the risk factors and clinical course of the other renal diseases that may also occur as a complication of HIV infection. This study was undertaken to compare HIVAN to the spe...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00865.x
更新日期:2004-09-01 00:00:00
abstract::Long-term outcomes of kidney allografts have shown only marginal improvement over the last three decades, despite the remarkable improvement in acute rejection and one-year graft survival. Novel biomarkers of tubular injury may prevent irreversible damage to the tubulointerstitial compartment and improve allograft sur...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002772
更新日期:2008-03-01 00:00:00
abstract:BACKGROUND:Assessment of mRNA levels has the potential to predict renal outcome. The objective of this study was to optimize several steps in the protocol for obtaining cDNA from routine clinical kidney biopsy material. METHODS:RNA integrity was compared between different methods for extraction of RNA, synthesis of cD...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00366.x
更新日期:2004-01-01 00:00:00
abstract::To determine whether the induction of immune-mediated glomerular injury influences the formation of cyclooxygenase products by glomerular cells, we determined prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) (as the stable metabolite of TXA2) formation in isolated glomeruli of rats with passive Heymann nephritis (PHN...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.118
更新日期:1987-05-01 00:00:00
abstract::Long-term (5 years) treatment of 20 growth-retarded pre-pubertal children with chronic renal insufficiency (CRI) led to a significant (P < 0.00005) improvement in standardized height from -2.6 at baseline to -0.7 at five years. Eight patients were paused after reaching target height (50th centile midparental height) a...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1038/ki.1996.108
更新日期:1996-03-01 00:00:00
abstract::The international guideline from Kidney Disease: Improving Global Outcomes suggests a hemoglobin target of 11 to 12 g/dl for children with chronic kidney disease. However, information to support this proposal is very limited in the pediatric population. Because of controversy, the unmet need is the establishment of an...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.10.006
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Non-(1-84) parathyroid hormone (PTH) fragments are large circulating carboxyl-terminal (C) fragments with a partially preserved amino-terminal (N) structure. hPTH (7-84), a synthetic surrogate, has been demonstrated to exert biologic effects in vivo and in vitro which are opposite to those of hPTH (1-34) on ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00493.x
更新日期:2005-09-01 00:00:00
abstract::Pain was surveyed via structured interview and the McGill Pain Questionnaire in 53 dialysis and 27 transplant patients. Increased patient control over the dialysis procedure was not associated with a reduction in pain though perceived control may have been. Compliance with the dialysis regimen did not predict pain and...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1982.108
更新日期:1982-06-01 00:00:00
abstract::The high serum fibroblast growth factor 23 (FGF23) levels in patients with acute kidney injury (AKI) and chronic kidney disease (CKD) are associated with increased morbidity and mortality. Mice with folic acid-induced AKI had an increase in bone FGF23 mRNA expression together with an increase in serum FGF23 and severa...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.02.026
更新日期:2018-08-01 00:00:00
abstract:BACKGROUND:Cardiovascular death continues to be a major problem in renal failure. Structural abnormalities of the heart and the vasculature contribute to the increased cardiovascular risk. They are ameliorated by angiotensin-converting enzyme (ACE) inhibitors, but because of the nonspecifity of ACE inhibition, it is un...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00163.x
更新日期:2000-07-01 00:00:00
abstract::We have previously shown that ultrasonography can detect hyperechogenic crystal deposits in the kidney medulla of patients with gout. In this cross-sectional study we investigated the frequency and clinical correlates of hyperechogenic kidney medulla in 502 consecutive primary consultants for gout (ACR/EULAR criteria)...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.08.024
更新日期:2021-01-01 00:00:00