Abstract:
BACKGROUND:The clinical use of cyclosporine (CsA) is limited by its nephrotoxicity. Apoptosis, perhaps instigated by increased nitric oxide synthase (NOS) activity, may play a role in such toxicity. METHODS:Human mesangial cells, human tubular cells, human umbilical vein endothelial cells, or murine endothelial cells were cultured with CsA at final concentrations of 0 to 1000 ng/mL for 4 to 24 hours. As inhibitors of apoptosis, 0.01 mol/L L-nitromethylarginine (L-NAME) or 1 microg/mL cycloheximide (CHX) was added, whereas 0.01 mol/L sodium nitroprusside (as a nitric oxide donor) was used as a positive control. Apoptosis was assessed by using TUNEL method and by DNA fragmentation by electrophoresis. In addition, NOS enzymatic activity, Northern blots for inducible NOS (iNOS) mRNA, and immunohistochemically demonstrable iNOS protein were evaluated. RESULTS:Within 12 to 24 hours, CsA significantly increased the fraction (8 to 35%) of apoptotic cells in each cell line, according to the dose. Fragmentation of DNA confirmed apoptosis. L-NAME and CHX inhibited the phenomenon, whereas sodium nitroprusside enhanced it. Each cell line significantly increased NOS activity in response to CsA, an effect blunted by L-NAME and CHX. Neither inhibitor modified the increased iNOS mRNA expression elicited by CsA. Positive staining for both iNOS and p53 proteins was observed in all cell lines incubated with CsA that were inhibited by CHX; L-NAME inhibited only p53 staining. CONCLUSIONS:CsA induces apoptosis in various renal cell lines, and this effect is mediated by the induction of iNOS via p53. These effects may contribute to the acellular fibrosis characteristic of late CsA nephrotoxicity.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Amore A,Emancipator SN,Cirina P,Conti G,Ricotti E,Bagheri N,Coppo Rdoi
10.1046/j.1523-1755.2000.00999.xsubject
Has Abstractpub_date
2000-04-01 00:00:00pages
1549-59issue
4eissn
0085-2538issn
1523-1755pii
S0085-2538(15)46904-2journal_volume
57pub_type
杂志文章abstract:BACKGROUND:Mice overexpressing thymic stromal lymphopoietin (TSLP) develop mixed cryoglobulinemia with renal disease closely resembling human cryoglobulin-associated membranoproliferative glomerulonephritis (MPGN), including glomerular deposits of immunoglobulins and complement. We assessed the effect of complement inh...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00495.x
更新日期:2004-04-01 00:00:00
abstract::Nitric oxide is generated from L-arginine by nitric oxide synthase (NOS), an enzyme that exists in several isoforms. Some studies found that a polymorphism (G894T) in the endothelial NOS gene was associated with decreased nitric oxide bioactivity and vascular complications. However, it is not known whether the enzyme ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.574
更新日期:2009-02-01 00:00:00
abstract:BACKGROUND:Chemokine receptor 5 (CCR5) plays an important role in the recruitment of monocytes and T cells in inflammation and experimental studies suggest that CCR5 might be involved in the pathogenesis of IgA nephropathy. A mutation in the CCR5 gene (CCR5 Delta32), leading to a nonfunctional receptor, was recently de...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00057.x
更新日期:2005-01-01 00:00:00
abstract:UNLABELLED:The paracellular permeability of opossum kidney cells, a proximal tubule cell line. BACKGROUND:The regulation of the unusually leaky paracellular pathway of the proximal tubule is poorly understood partially because of the lack of an appropriate in vitro cell model. In this study, we determined whether the ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00787.x
更新日期:1999-12-01 00:00:00
abstract:BACKGROUND:Patients initiating dialysis after a failed kidney transplant are a subgroup of chronic kidney disease (CKD) patients who have not been characterized. Exposure to immunosuppressive medications differentiates these patients from the general incident end-stage renal disease (ESRD) population. METHODS:Data fro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00373.x
更新日期:2002-06-01 00:00:00
abstract:BACKGROUND:Nephrotic syndrome is associated with abnormal lipoprotein metabolism and increased risk of coronary heart disease. Endothelial dysfunction, an early phase of atherogenesis that manifests as impaired flow-mediated dilation (FMD) of the peripheral circulation, may link these associations. METHODS:We examined...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00785.x
更新日期:2001-07-01 00:00:00
abstract::In membranous nephropathy (MN) overproduction of matrix by glomerular epithelial cells (GEC) is believed to be responsible for glomerular basement membrane thickening and spikes. We studied experimental MN in rats (passive Heymann nephritis, PHN) at 5, 10 and 30 days. PHN rats exhibited a marked increase in GEC immuno...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.294
更新日期:1996-07-01 00:00:00
abstract:BACKGROUND:The purpose of this study was to evaluate the renoprotective effect as reflected by short-term changes in albuminuria of ultrahigh doses of irbesartan in type 2 diabetic patients with microalbuminuria. METHODS:This double-masked randomized crossover trial included 52 (41 males) hypertensive type 2 diabetic ...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1523-1755.2005.00511.x
更新日期:2005-09-01 00:00:00
abstract::Fifty-one adults with HIV infection, including 20 chronic hemodialysis patients with superimposed HIV infection and 31 patients with HIV-associated nephropathy requiring chronic maintenance hemodialysis were followed to evaluate survival on outpatient dialysis in relation to the clinical stage of the HIV infection. Re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.172
更新日期:1988-08-01 00:00:00
abstract::11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) transforms endogenous glucocorticoids to their respective "biologically inert" 11-dehydro derivatives. A decrease in enzyme activity allows glucocorticoids to induce mineralocorticoid-like renal sodium retention. Since positive sodium balance is required for optimum ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.91
更新日期:1994-03-01 00:00:00
abstract::The goals of the present study were twofold: first, to assess the renal excretory and hormonal responses to chronic water restriction in dogs whose sodium retaining mechanisms had been stimulated through dietary sodium (Na+) deprivation; second, to determine the mediator(s) of the natriuresis which was observed with w...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.121
更新日期:1986-06-01 00:00:00
abstract::Mechanisms responsible for renal hemodynamic alterations were studied in jaundiced (by bile-duct ligation) rabbits (BDL) 10 days after ligation of the biliary tract, in comparison with sham-operated rabbits (SO). Arterial hematocrit, plasma volume, blood pressure, abdominal inferior vena cava pressure, and heart rate ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1980.25
更新日期:1980-02-01 00:00:00
abstract:BACKGROUND:Arteriovenous (AV) fistulas used for hemodialysis access may affect cardiac load by increasing the preload while decreasing the afterload. In dogs, AV fistulas have also been shown to affect coronary perfusion negatively. We investigated the net effect of AV fistulas on cardiac oxygen supply and demand. MET...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00433.x
更新日期:1999-05-01 00:00:00
abstract::The role of glutathione (GSH) in the preservation of renal function and the pathogenesis of renal injury has been investigated using the isolated perfused rat kidney as a model. In kidneys perfused for 80 min with 5 mM glucose as the only exogenous substrate, tissue GSH becomes depleted, renal function deteriorates, a...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.142
更新日期:1983-08-01 00:00:00
abstract:BACKGROUND:Nitric oxide inactivation by superoxide impairs endothelium-dependent vasodilation and plays a role in various forms of hypertension. Almost no data exist regarding hypertension secondary to chronic renal failure. Previous studies have shown that endothelium-related relaxations, secondary to decreased nitric...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00166.x
更新日期:2002-02-01 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
abstract::Anemia can contribute to chronic allograft injury by limiting oxygen delivery to tissues, particularly in the tubulointerstitium. To determine mechanisms by which erythropoietin (EPO) prevents chronic allograft injury we utilized a rat model of full MHC-mismatched kidney transplantation (Wistar Furth donor and Lewis r...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.473
更新日期:2012-05-01 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::Intravital multiphoton microscopy is a powerful tool to study kidney physiology in living animals. However, certain technical issues have curbed its usage to date, including limited depth of tissue penetration and high background emission of endogenous signals. Most previous studies have used the excitation range 700–...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.323
更新日期:2016-03-01 00:00:00
abstract::The purpose of this study was to explore risk factors affecting the incidence of chronic kidney disease (CKD) in general population. We conducted a 10-year follow-up study with 123 764 (male: 41 012, female: 82 752) adults aged 40 years and over who received community-based annual examinations. The primary outcome for...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002017
更新日期:2007-01-01 00:00:00
abstract::Progression of diabetic nephropathy appears directly related to renal tubulointerstitial injury, but the involved genes are incompletely delineated. To identify such genes, DNA microarray analysis was performed with RNA from renal proximal tubules (RPTs) of streptozotocin-induced diabetic Wistar rats, spontaneously di...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000206
更新日期:2006-03-01 00:00:00
abstract::A model of glomerular dynamics has been developed by using network thermodynamics and the SPICE 2 computer program to further explore the determinants of glomerular filtration. The model is designed to be holistic and self-adjusting, taking cognizance of and permitting quantitation of the secondary alterations in indi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1981.27
更新日期:1981-02-01 00:00:00
abstract::Myeloproliferative neoplasms are clonal hematopoietic stem cell disorders that can produce an undefined glomerulopathy. To better characterize the glomerular disease associated with myeloproliferative neoplasms, we evaluated features of 11 patients with myeloproliferative neoplasm-related glomerulopathy that included ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.147
更新日期:2011-10-01 00:00:00
abstract:BACKGROUND:Decreased red blood cell survival contributes to the anemia of chronic renal failure patients. Because patients on chronic dialysis therapy are frequently exposed to excessive complement activation, we investigated the susceptibility of this patient population to erythrocyte C5b-9 deposition, complement-medi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00277.x
更新日期:1999-02-01 00:00:00
abstract::The current study was undertaken to examine the effects of dithiothreitol (DDT), a sulfhydryl-reducing agent and heavy metal chelator, on the course of heavy metal-induced acute renal failure in the rat. Groups of rats in metabolic cages received uranyl nitrate (UN) alone, UN plus DTT, mercuric chloride (HgCl2) alone,...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1977.88
更新日期:1977-08-01 00:00:00
abstract::Metabolic changes due to chronic renal failure (CRF) were studied in isolated liver cells. In 14 CRF and 14 sham-operated rats, liver cells were isolated by the Berry and Friend method and incubated with various substrates in order to study gluconeogenesis, ureagenesis, ketogenesis, oxygen consumption as well as cytos...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.215
更新日期:1995-06-01 00:00:00
abstract::Systemic AA type amyloidosis with renal involvement is the major cause of morbidity and mortality in patients with familial Mediterranean fever (FMF). A histopathological examination is essential to achieve a definite diagnosis in systemic amyloidosis. The diagnostic yield of the procedure varies according to the biop...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.318
更新日期:1993-10-01 00:00:00
abstract::Proliferation of mesangial cells is frequently found in glomerulonephritis, such as IgA glomerulonephritis. Recent reports suggest that a brain/embryo-type myosin isoform (MIIB2) is involved in cell proliferation. We have studied the expression of MIIB2 in renal biopsy samples from patients with various renal diseases...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.191
更新日期:1996-05-01 00:00:00
abstract::The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) is thought to be a protective enzyme of the mineralocorticoid receptor (MR). We have previously demonstrated (Bonvalet et al, J Clin Invest 86:832-837, 1990) that 11 beta-OHSD is colocalized with MR along the rabbit nephron. In the present study, we examin...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.260
更新日期:1992-07-01 00:00:00
abstract::The pathologic and clinical features of 16 patients with dense intramembranous deposit disease are described. By light microscopy nine patients had membranoproliferative glomerulonephritis, five had focal segmental necrotizing glomerulonephritis with segmental epithelial crescents, four of whom also had a prominent tu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1984.71
更新日期:1984-04-01 00:00:00