Abstract:
BACKGROUND:The glomerular endothelial cell is a specialized microvascular cell type involved in the regulation of glomerular ultrafiltration. During gram-negative sepsis, glomerulonephritis, and acute renal failure, bacterial lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) may cause severe cell damage. Our aim was to study and compare the direct effects of TNF-alpha and LPS on the induction of apoptosis in bovine glomerular endothelial cells. METHODS:Primary bovine glomerular endothelial cells were stimulated with TNF-alpha or LPS, and apoptotic cell death was investigated by DNA fragmentation analysis, morphological studies, measurement of cytochrome c efflux and mitochondrial permeability transition, Bak, Bad, Bax, Bcl-2, Bcl-xL protein expression, and caspase-3-like protease activity. RESULTS:TNF-alpha, as well as LPS, elicited apoptotic cell death both time and concentration dependently. Along with DNA ladder formation, we detected the formation of 50 kbp high molecular weight DNA fragments, nuclear condensation, and mitochondrial permeability transition. Concerning all parameters, LPS signaling proved to be more rapid than TNF-alpha. Mechanistically, TNF-alpha-induced cell death was preceded by an efflux of mitochondrial cytochrome c into the cytosol and, subsequently, by a marked increase in the proapoptotic protein Bak and a decrease in the anti-apoptotic Bcl-xL protein content. Comparable but more pronounced effects were seen with LPS. Later, caspase-3-like protease activity was first detectable after 10 hours and was continuously increased up to 24 hours in both TNF-alpha- and LPS-stimulated cells. Correspondingly, we detected an extended cleavage of the nuclear enzyme poly(ADP-ribose) polymerase. Caspase inhibitors Z-Asp-CH2-DCB and Z-VAD-fmk blocked both TNF-alpha- and LPS-induced apoptosis in a comparable manner. Only Z-Asp-CH2-DCB was able to block apoptotic cell death completely. CONCLUSION:Both bacterial LPS and TNF-alpha potently induced apoptotic cell death in glomerular endothelial cells. Direct endotoxin-induced apoptosis may therefore be relevant in the progression of acute renal failure, which is a frequent complication of gram-negative sepsis.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Messmer UK,Briner VA,Pfeilschifter Jdoi
10.1046/j.1523-1755.1999.00473.xsubject
Has Abstractpub_date
1999-06-01 00:00:00pages
2322-37issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(15)46194-0journal_volume
55pub_type
杂志文章abstract:BACKGROUND:Nephrotoxic glomerulonephritis is induced by the administration of antibody against the glomerular basement membrane (GBM). We demonstrated previously that Fc receptors for immunoglobulin G (IgG) (FcgammaR) play crucial roles in the induction of accelerated nephrotoxic glomerulonephritis by using FcRgamma-de...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00203.x
更新日期:2003-10-01 00:00:00
abstract::Polycystic kidney disease progresses more rapidly in men than in women. To investigate the basis for this sexual dimorphism, we exposed Madin-Darby canine kidney (MDCK) cells grown on collagen-coated cell culture inserts to control media, or to estradiol or testosterone (1 nM-1 microM). Compared to control and estradi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.211
更新日期:1997-05-01 00:00:00
abstract::In experimental membranous nephropathy, antibody binding to glomerular epithelial cell membrane antigens results in complement activation and formation of complement C5b-9 membrane attack complexes in glomeruli. During active disease, the C5b-9 complexes are shed into the urine. To test the hypothesis that a similar m...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.242
更新日期:1991-09-01 00:00:00
abstract::Zhang and co-workers report on the renoprotective role of the vitamin D receptor (VDR) in diabetic nephropathy using the method of streptozotocin-induced hyperglycemia in wild-type and VDR(-/-) mice. Also, experiments with cultured mesangial cells and podocytes confirm the effect of the active vitamin D metabolite 1,2...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002693
更新日期:2008-01-01 00:00:00
abstract::The purpose of these studies was to test the hypothesis that Randall's plaque develops in unique anatomical sites of the kidney and their formation is conditioned by specific stone-forming pathophysiologies. We performed intraoperative papillary biopsies from kidneys of idiopathic-calcium oxalate (CaOx), intestinal by...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5000238
更新日期:2006-04-01 00:00:00
abstract:BACKGROUND:The beneficial effect of blood transfusions before cadaveric renal transplantation on allograft survival, although previously well documented, has become controversial in light of their adverse effects. Recently, it has been suggested that their clinical benefits are due to HLA-DR sharing between the blood d...
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:10.1046/j.1523-1755.2001.00805.x
更新日期:2001-07-01 00:00:00
abstract::Many approaches to blocking profibrotic TGFbeta overexpression are under way. Therapeutic targeting of TGFbeta-Smad signaling holds promise for slowing or halting progressive renal disease. In this issue, Fukasawa et al., using the unilateral ureteral obstruction model, provide a new target for therapeutic interventio...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5000260
更新日期:2006-05-01 00:00:00
abstract::Tubulointerstitial nephritis antigen (TIN-ag) is an extracellular matrix (ECM) glycoprotein that has been recently isolated and cloned from the rabbit kidney. It is an integral component of the basal lamina, and unlike other basement membrane proteins it is exclusively expressed in the tubular basement membranes (TBMs...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.375
更新日期:1997-09-01 00:00:00
abstract:BACKGROUND:C-peptide has been reported to have biological effects on renal function early in the course of diabetes. This investigation was initiated to elucidate and amplify these findings with respect to protein leakage, hyperfiltration and renal functional reserve in diabetic rats. METHODS:Acute effects of 140 minu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00074.x
更新日期:1998-09-01 00:00:00
abstract:BACKGROUND:Prolactin (PRL), originally identified as an anterior pituitary hormone exhibiting lactogenic activity, is now recognized as a versatile hormone expressed in a wide variety of tissues. METHODS:In this study, the expression of PRL in the mouse kidney was investigated by solution-phase and in situ reverse tra...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.055003833.x
更新日期:1999-03-01 00:00:00
abstract:BACKGROUND:Reactive carbonyl compounds (RCOs) present in peritoneal dialysis (PD) fluid have been incriminated in the progressive deterioration of the peritoneal membrane in long-term PD patients. They are initially present in fresh conventional heat-sterilized glucose PD fluid and are supplemented during dwell time by...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00732.x
更新日期:2003-01-01 00:00:00
abstract::A second generation hepatitis C virus recombinant immunoblot assay (RIBA) was used to screen stored perioperative serum from 641 renal allograft recipients. One hundred and nine (17%) were anti-HCV positive at the time of transplant. RIBA positivity was found to be an independent predictor of post-transplant liver dis...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.29
更新日期:1994-01-01 00:00:00
abstract::The kidney is a likely source for some urinary epinephrine (E) since adrenalectomized animals and humans continue to excrete urinary E and the human kidney contains E synthesizing enzymes. We studied subjects during an intravenous infusion of 3H-E to determine the fraction of urinary E derived from the kidney. Eight n...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.40
更新日期:1997-01-01 00:00:00
abstract::Previous studies have demonstrated that dietary potassium deprivation in healthy human subjects eating diets otherwise containing normal quantities of NaCl is accompanied by an increase in urinary calcium excretion. This increase in urinary Ca excretion occurs in association with reductions in urinary Na and Cl excret...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1995.134
更新日期:1995-03-01 00:00:00
abstract::We have previously identified the engulfment and cell motility 1 (ELMO1) as a susceptibility gene for diabetic nephropathy. To elucidate the role of ELMO1 in the pathogenesis of chronic renal injury, we examined the expression of Elmo1 in the kidney of a rat model for chronic glomerulonephritis (uninephrectomy plus an...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001939
更新日期:2006-11-01 00:00:00
abstract:BACKGROUND:The characteristic feature of Goodpasture disease is the occurrence of an autoantibody response to the noncollagenous domain of the alpha3 chain of type IV collagen [alpha3(IV)NC1] in the alveolar and glomerular basement membrane. These antibodies are associated with the development of a rapidly progressive ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.055003936.x
更新日期:1999-03-01 00:00:00
abstract:BACKGROUND:The purpose of this study was to examine the relationship between glomerular filtration rate (GFR) measured at 5 years' diabetes duration and annual urine albumin excretion in a prospective cohort of children with type 1 diabetes (T1DM). METHODS:Three hundred and eight children were followed from diagnosis ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00590.x
更新日期:2005-10-01 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::Bikunin is a chondroitin-sulphate containing serum protein with a Stokes-Einstein radius and a negative net charge close to those of serum albumin. The plasma half life of bikunin is about 10 minutes, and approximately half of its clearance occurs in the kidneys. The quantitative role of glomerular filtration in the r...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.147
更新日期:1997-04-01 00:00:00
abstract::The mean renal tubular diameters, number of tubules per unit of cross-sectional area, and fraction of the total volume occupied by each medullary structure were determined at various levels of the renal medulla of the rat and rabbit. Statistical estimates of anatomic variables were made using spatial sampling techniqu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1977.118
更新日期:1977-11-01 00:00:00
abstract:BACKGROUND:It is still unclear whether age per se is associated with preservation of renal functional reserve, that is, of the increase in glomerular filtration rate (GFR) induced by appropriate vasodilating stimulus. METHODS:To gain insights into this issue, we evaluated the renal response to a maximal vasodilating s...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0590031052.x
更新日期:2001-03-01 00:00:00
abstract:BACKGROUND:Urea kinetic modeling (UKM) and food records are widely used to assess the dialysis adequacy. Clinicians use these methods in individual patients to decide whether the dialysis prescription should be adjusted. We determined the variation in UKM parameters and dietary intake within individual patients in orde...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1046/j.1523-1755.1999.00412.x
更新日期:1999-05-01 00:00:00
abstract:BACKGROUND:While tubular cell death is a characteristic of acute renal failure (ARF), the molecular mechanisms that modulate this cell death are unclear. Cell fate in acute renal failure hinges on a balance of survival and mortality factors in a changing environment. We further explored this issue by studying selected ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00925.x
更新日期:2000-03-01 00:00:00
abstract::Extracellular fluid volume expansion is known to produce exaggerated natriuresis in essential hypertension. In order to assess the role of hemodynamic and intrarenal physical factors upon natriuretic response to central volume expansion, two hour water immersion (WI) experiments were made in six uncomplicated essentia...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.79
更新日期:1988-04-01 00:00:00
abstract::The in vitro heparin sensitivity of 18 nephrotic children was compared with that of 10 normal children and 13 children with other renal diseases. The influence of age on the heparin sensitivity of 52 normal subjects (aged 12 to 85 years) was also studied. The heparin sensitivity was calculated from the dose-response c...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.155
更新日期:1987-06-01 00:00:00
abstract:BACKGROUND:Idiopathic nephrotic syndrome is a proteinuric disease secondary to the release of a nonidentified circulating glomerular permeability factor by T cells. Because specificities of T-cell activation in idiopathic nephrotic syndrome remain unknown, we evaluated transcriptional activation of T cells in nephrotic...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00322.x
更新日期:2005-06-01 00:00:00
abstract::Angiotensin converting enzyme (ACE) inhibitors are known to lower urinary protein excretion in human renal disease. This proteinuria lowering effect of ACE inhibition has been hypothesized to be a result of renal hemodynamic changes due to the inhibition of angiotensin II (Ang II) production. To test this hypothesis w...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1991.268
更新日期:1991-10-01 00:00:00
abstract::The microcirculation is regulated by oxygen gradients and by endothelial release of nitric oxide, which can react with hemoglobin to form S-nitroso derivatives. Here we induced flow-mediated dilatation of the brachial artery in response to ischemia in 141 non-diabetic patients with stage 3-4 chronic kidney disease who...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.63
更新日期:2009-06-01 00:00:00
abstract::In contrast to other nonsteroidal anti-inflammatory drugs (NSAIDs), sulindac has been reported to inhibit systemic prostaglandins (PGs) while not affecting renal PGs. We studied 11 normal volunteers who received placebo, ibuprofen, naproxen, or sulindac in a randomized, double-blind fashion. After control periods asse...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1985.11
更新日期:1985-01-01 00:00:00
abstract::The role of endogenous atrial natriuretic peptide (ANP) in the immediate response of sodium excretion to unilateral nephrectomy (UNX) was investigated in anesthetized euvolemic rats through measurement of UNX-induced change in plasma ANP concentration and the response of the remaining kidney to UNX following administr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.178
更新日期:1993-06-01 00:00:00