Abstract:
BACKGROUND:We have recently demonstrated an increase in apoptosis in Han:SPRD rat kidneys with autosomal-dominant polycystic kidney disease (ADPKD). Caspase-3 and caspase-7 are major mediators of apoptosis. There are two pathways of caspase-3 and caspase-7-mediated apoptosis: (1) the "extrinsic" pathway involving the death receptor Fas, Fas ligand (FasL), and caspase-8 and (2) the "mitochondrial" or "intrinsic" pathway involving Bcl-2 proteins, caspase-2, cytochrome c release, and caspase-9. The aim of the present study was to investigate the pathways of apoptosis in 3-week-old Han:SPRD rats with ADPKD. METHODS:Fluorescent substrates were used to measure caspase activity. mRNA and protein was determined by ribonuclease protection assays and immunoblotting, respectively. The effect of caspase inhibitors on caspase activity in polycystic kidneys was determined. RESULTS:Caspase-3 and caspase-7 activity was more than 100% increased in homozygous (Cy/Cy) compared to heterozygous (Cy/+) and normal littermate control (+/+) kidneys. Ribonuclease protection assays demonstrated no difference in caspase-3 mRNA. On immunoblotting, there was an increase in the proform of caspase-3 and caspase-7 in Cy/Cy compared to +/+ and Cy/+ kidneys. Caspase-8 and caspase-9 activity was more than 100% increased in Cy/Cy compared to Cy/+ and +/+ kidneys. On immunoblotting, there was an increase of the proform of both caspase-8 and caspase-9 in Cy/Cy kidneys. There was also an increase in cytochrome c release into the cytosol and an increase in caspase-2 protein and activity in Cy/Cy kidneys. On ribonuclease protection assay there was no difference in FasL mRNA between +/+, Cy/+, and Cy/Cy kidneys. Short-term treatment of Cy/Cy rats with the caspase inhibitor IDN-8050 resulted in inhibition of caspase-3 and caspase-7 activity in the kidney. CONCLUSION:In Cy/Cy kidneys with ADPKD, there was an increase of the proform of caspase-9, an increase in cytochrome c release into the cytosol, and an increase in caspase-2 protein and activity demonstrating involvement of the intrinsic pathway. There was an increase in the proform of caspase-8 demonstrating involvement of the extrinsic pathway. No differences in FasL mRNA were seen suggesting that the extrinsic pathway is independent of the death receptor ligand, FasL.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Tao Y,Kim J,Stanley M,He Z,Faubel S,Schrier RW,Edelstein CLdoi
10.1111/j.1523-1755.2005.00155.xsubject
Has Abstractpub_date
2005-03-01 00:00:00pages
909-19issue
3eissn
0085-2538issn
1523-1755pii
S0085-2538(15)50536-Xjournal_volume
67pub_type
杂志文章abstract::Intestinal regulation of oxalate absorption is a complex mechanism, not exclusively reliant on the oxalate-degrading anaerobe Oxalobacter formigenes. Using metagenomics, Miller et al. were able to describe a network of bacterial taxa co-occurring with Oxalobacter formigenes in fecal samples from non-stone forming cont...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2019.03.020
更新日期:2019-07-01 00:00:00
abstract:BACKGROUND:Fistula failure has been classified as early and late. Early failure refers to those cases in which the arteriovenous (AV) fistula never develops to the point that it can be used or fails within the first 3 months of usage. It has been common practice to abandon these early failures; however, aggressive eval...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00210.x
更新日期:2003-10-01 00:00:00
abstract::Transplanted organs express allogeneic epitopes against which a recipient's immune system mounts a destructive response. In the absence of a reliable strategy for induction of donor-specific tolerance, therapeutic immunosuppression remains the best prospect to prevent rejection, but exposes recipients to increased ris...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.268
更新日期:2015-12-01 00:00:00
abstract::Intravascular hemolysis is relatively rare but can lead to acute kidney injury (AKI), from increased destruction of erythrocytes and release of free hemoglobin. Since hemolysis and hemoglobinuria are known causes of acute kidney injury we sought to define clinicopathologic findings and outcomes of patients with hemoly...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2019.08.026
更新日期:2019-12-01 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::The transition between the glomerulus and the proximal tubule was studied by light and electron microscopy in perfusion-fixed rabbit kidneys. In most nephrons a transitional segment of tubule occurred between the Bowman's capsule and the proximal tubule proper. This initial part of the tubule was lined by flattened ce...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1975.22
更新日期:1975-03-01 00:00:00
abstract:BACKGROUND:Optimal nutrient intake is important in the maintenance of a positive nitrogen balance in hemodialysis (HD) patients. The objectives of this study were (1) to assess the influence of two levels of protein intakes on nitrogen balance in stable adult HD patients, and (2) to identify a minimum level of protein ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00171.x
更新日期:2000-07-01 00:00:00
abstract::The maximum rate of inorganic phosphorus (P1) reabsorption (Tmp1) was measured during phosphate infusion in chronically parathyroidectomized rats. In either initially hydropenic rats or others which underwent moderate preliminary saline loading, Tmp1 tended to rise during early phosphate infusion and then decline, so ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1975.85
更新日期:1975-08-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) are key mediators of adverse peritoneal membrane remodeling in peritoneal dialysis eventually leading to ultrafiltration failure. Both are pleiotropic growth factors with cell type-dependent regulation of expression and biological eff...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.217
更新日期:2013-12-01 00:00:00
abstract:BACKGROUND:Approximately 8% of autosomal-dominant polycystic kidney disease (ADPKD) patients have intracranial aneurysms. The risk of growth and rupture of those discovered by presymptomatic screening is key to the feasibility and success of a screening program. This study was initiated to ascertain this risk. METHODS...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00572.x
更新日期:2004-05-01 00:00:00
abstract:BACKGROUND:We hypothesized that increasing small solute clearance in peritoneal dialysis (PD) would lead to improvements in patient health-related quality of life (HRQOL). METHODS:Patients were randomized to a control group [standard 4 x 2 L continuous ambulatory peritoneal dialysis (CAPD)] and an intervention group (...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1523-1755.2005.00175.x
更新日期:2005-03-01 00:00:00
abstract::Pathologic calcification is a significant cause of increased morbidity and mortality in patients with chronic kidney disease. The precise mechanisms of ectopic calcification are not fully elucidated, but it is known to be caused by an imbalance of procalcific and anticalcific factors. In the chronic kidney disease pop...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2015.12.046
更新日期:2016-05-01 00:00:00
abstract::During online hemodiafiltration, patients are directly infused with sterile substitution solutions to maintain fluid balance. Adequate water treatment and a well-organized quality control process are essential to provide non-pyrogenic fluids with consistent optimal quality. We sought to assess water quality, the water...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.245
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND:The tissue renin-angiotensin system (RAS) may modulate the structural and functional changes that occur in the diabetic kidney. METHODS:Hypertensive transgenic (mREN-2)27 rat (TGR) that exhibit increased tissue renin expression were administered streptozotocin (STZ, diabetic) or citrate buffer (non-diabetic...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00019.x
更新日期:1998-08-01 00:00:00
abstract::Macrophages are inflammatory cells with important roles in the propagation of renal injury. More recently they have also been shown to be important in the resolution of inflammation. Wang et al. show that macrophages can be modulated ex vivo by cytokine stimulation, localize to renal tissue, and slow progression of ex...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002332
更新日期:2007-08-01 00:00:00
abstract::Unidirectional 32P-phosphate and 3H-mannitol fluxes were simultaneously measured, at two minutes intervals, in frog urinary bladders. The spontaneous or externally imposed transepithelial potential (PD) and short circuit current (SCC) were also recorded in most experiments. It was observed that: (1) Phosphate transfer...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.9
更新日期:1988-01-01 00:00:00
abstract::In normal subjects, beta-adrenergic stimulation lowers the serum potassium, whereas alpha-stimulation raises it. Epinephrine, a mixed alpha and beta agonist, acutely lowers the blood potassium in normal subjects, but not in patients with end-stage renal disease. This study was designed to determine whether the resista...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.321
更新日期:1991-12-01 00:00:00
abstract:BACKGROUND:The detailed mechanisms of glucocorticoid action in idiopathic nephrotic syndrome and progressive glomerulonephritides have not been clearly elucidated. The pharmacological actions of glucocorticoids are mediated by their binding to an intracellular protein, the glucocorticoid receptor (GR). The determinatio...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00503.x
更新日期:1999-07-01 00:00:00
abstract::Recent studies of timing of dialysis initiation have challenged the recent trend to earlier initiation of therapy. The observed outcomes though are a consequence of the balance between the risks of advanced uremia versus the inherent dangers relating to dialysis therapy itself. Many of these risks are inherent in how ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2012.133
更新日期:2012-08-01 00:00:00
abstract::Among patients with proteinuric chronic kidney disease (CKD), current guideline recommendations mandate the use of agents blocking the renin angiotensin aldosterone system (RAAS) as first-line antihypertensive therapy based on randomized trials demonstrating that RAAS inhibitors are superior to other antihypertensive ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2017.08.038
更新日期:2018-02-01 00:00:00
abstract::It has been proposed that one of the primary events in the development of essential hypertension is a growth-related process initiated as early as during fetal development. Differences in kidney size have been observed between most rat models of hypertension and their respective controls. In this study, we analyzed re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00938.x
更新日期:1998-06-01 00:00:00
abstract:BACKGROUND:Advanced glycation of proteins and their attendant advanced glycation end products (AGEs) contribute to the complications associated with diabetes mellitus or uremia. Regulatory mechanisms of AGE formation in vivo remain an issue of particular interest. We investigated a role of the glyoxalase detoxification...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00051.x
更新日期:2001-12-01 00:00:00
abstract::The kidneys excrete the daily acid load mainly by generating and excreting ammonia but the underlying molecular mechanisms are not fully understood. Here we evaluated the role of the inwardly rectifying potassium channel subunit Kir4.2 (Kcnj15 gene product) in this process. In mice, Kir4.2 was present exclusively at t...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2019.09.028
更新日期:2020-02-01 00:00:00
abstract::IgG4-related disease is a recently recognized multi-organ disorder characterized by high levels of serum IgG4 and dense infiltration of IgG4-positive cells into several organs. Although the pancreas was the first organ recognized to be affected by IgG4-related disorder in the syndrome of autoimmune pancreatitis, we pr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.271
更新日期:2010-11-01 00:00:00
abstract::Fibroblast growth factor 23 (FGF23) is a phosphate-regulating hormone that acts primarily on the kidney and parathyroid. With declining kidney function there is an increase in circulating FGF23 levels, which is associated with vascular calcification and mortality in chronic kidney disease. Whether FGF23 exerts direct ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.332
更新日期:2014-05-01 00:00:00
abstract::Because of high risk of cardiovascular disease, patients with chronic kidney disease may benefit from cholesterol-lowering therapy beyond statins. A cost-effectiveness analysis of adding ezetimibe to high-dose statins for primary cardiovascular disease prevention in patients with non-dialysis-dependent chronic kidney ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2019.02.029
更新日期:2019-07-01 00:00:00
abstract:BACKGROUND:A need exists for a therapy that lowers parathyroid hormone (PTH) without increasing calcium x phosphorus in patients with secondary hyperparathyroidism. The calcimimetic AMG 073 increases the sensitivity of the parathyroid calcium-sensing receptor to extracellular calcium, thereby reducing PTH secretion. Co...
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.1523-1755.2003.00720.x
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:The podocyte is the focus of much research into the mechanisms of renal disease progression, and the number of podocytes per glomerulus has thus become a parameter of much interest. When counting podocytes, the actual particle counted is the cell nucleus. The majority of published studies estimating podocyte...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1111/j.1523-1755.2004.00787.x
更新日期:2004-08-01 00:00:00
abstract:BACKGROUND:Microalbuminuria (MA) is a strong predictor of cardiovascular disease, but its causes are incompletely understood. Hyperhomocysteinemia is a recently recognized risk factor for cardiovascular disease independent of established risk factors. It is not known whether hyperhomocysteinemia is associated with MA, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.4495353
更新日期:1998-07-01 00:00:00
abstract:BACKGROUND:The substitution of tryptophan for glycine at amino acid 460 (Gly460Trp polymorphism) of the alpha-subunit of the heterodimeric cytoskeleton protein adducin increases renal sodium reabsorption and may be involved in the pathophysiology of essential hypertension. In the present study, we investigated in multi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00691.x
更新日期:2002-12-01 00:00:00