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 system of precursor reactive carbonyl compounds (RCOs) in the in vivo AGE formation. METHODS:Plasma levels of AGEs [pentosidine and Nepsilon-carboxymethyllysine (CML)], their RCO precursors, d-lactate (the final product resulting from the glyoxalase detoxification pathway), as well as of various compounds known to generate AGE precursors and surrogate markers for oxidative stress (antioxidant enzymes and glutathione), were measured in both hemodialysis (HD) patients and normal subjects. The activity and protein expression of glyoxalase I, an enzyme essential for the detoxification of alpha-oxoaldehydes, in red blood cells (RBC) were also examined. RESULTS:In one 69-year-old lady who had been on hemodialysis (HD) for three years and had suffered from recurrent cardiovascular complications despite the absence of significant risk factors, plasma levels of pentosidine (77.3 +/- 2.4 pmol/mg protein) and CML (330.8 +/- 8.2 pmol/mg protein) were markedly elevated as compared to other HD patients (N = 20: 26.6 +/- 11.8 pmol/mg protein for pentosidine and 224.4 +/- 51.7 pmol/mg protein for CML). The plasma level of RCO precursors for pentosidine and CML was also higher in this patient than in other HD patients. Further investigation disclosed a very low activity in RBC of glyoxalase I (1.5 +/- 0.4 mU/106 RBC), as compared to other HD patients (3.9 +/- 0.6 mU/106 RBC) or normal subjects (4.0 +/- 0.6 mU/106 RBC). The glyoxalase I protein level, assessed in RBC by immunoblot analysis with a specific antibody, was markedly lower than that observed in HD patients and normal subjects. The causes of this deficiency remain unknown. Nucleotide sequencing of the products of reverse transcription-polymerase chain reaction from the patient's mononuclear cells revealed no genetic mutation within the coding region of the glyoxalase I gene. Plasma d-lactate level was also in the lower range (0.18 +/- 0.03 mg/dL) of the values measured in the other HD patients (0.27 +/- 0.09 mg/dL) and normal subjects (0.35 +/- 0.12 mg/dL). The plasma levels of various compounds known to generate AGE precursors (glucose, lipids and ascorbic acid) were either normal or low. The surrogate markers for oxidative stress such as antioxidant enzymes (glutathione peroxidases and superoxide dismutase) and glutathione were all within the range observed in the other HD patients. CONCLUSION:The unusually high levels of AGEs in this patient implicate a deficient glyoxalase detoxification of RCO precursors. The present clinical observation implicates, to our knowledge for the first time, the glyoxalase detoxification system and, in particular, glyoxalase in the actual level of AGEs in a uremic patient.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Miyata T,van Ypersele de Strihou C,Imasawa T,Yoshino A,Ueda Y,Ogura H,Kominami K,Onogi H,Inagi R,Nangaku M,Kurokawa Kdoi
10.1046/j.1523-1755.2001.00051.xsubject
Has Abstractpub_date
2001-12-01 00:00:00pages
2351-9issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(15)48129-3journal_volume
60pub_type
杂志文章abstract::Prior studies showed conflicting results regarding the association between 25-hydroxyvitamin D (25(OH)D) levels and mineral metabolism in end-stage renal disease. In order to determine whether the bioavailable vitamin D (that fraction not bound to vitamin D-binding protein) associates more strongly with measures of mi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.19
更新日期:2012-07-01 00:00:00
abstract::As new components of the renin-angiotensin system (RAS) are elucidated, our understanding of the complexities of their interactions also advances. Previous studies have determined that podocytes possess a local RAS that can generate angiotensin II. Podocytes have also been shown to express angiotensin-converting enzym...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2012.127
更新日期:2012-08-01 00:00:00
abstract:BACKGROUND:Podocytes are highly differentiated glomerular epithelial cells with limited potential to divide. They are responsible for maintaining and supporting the glomerular basement membrane so as to facilitate efficient filtration. The hypothesis tested was whether the development of glomerulosclerosis in the purom...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.060003957.x
更新日期:2001-09-01 00:00:00
abstract::Spontaneous and aspirated blood samples were collected from the welling points of surface efferent arterioles in the rat kidney. The amount of tubular reabsorbate in each sample was calculated from measurements of the inulin concentration in the sample and systemic arterial plasma. Both spontaneous and aspirated sampl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1984.44
更新日期:1984-03-01 00:00:00
abstract::Acute kidney injury (AKI) activates pathways of cell death and cell proliferation. Although seemingly discrete and unrelated mechanisms, these pathways can now be shown to be connected and even to be controlled by similar pathways. The dependence of the severity of renal-cell injury on cell cycle pathways can be used ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2009.224
更新日期:2009-09-01 00:00:00
abstract::We investigated the effects of epidermal growth factor (EGF) and arginine vasopressin (AVP) on Raf-1-MAP kinase cascade, including Raf-1-kinase (Raf-1-K), MAP kinase kinase (MAPKK), MAP kinase (MAPK) and S6 kinase (S6K) in Madin-Darby canine kidney (MDCK) cells. In a dose-dependent manner (10(-10) M to 10(-6) M), EGF ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.346
更新日期:1995-09-01 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:BACKGROUND:Various gene transfer vectors as well as delivery systems have been developed; however, many problems remain to be solved. We already achieved a technique to introduce genes into glomerular mesangial cells by hemagglutinating virus of Japan (HVJ) liposome-mediated gene transfer via renal artery. The main lim...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0590041390.x
更新日期:2001-04-01 00:00:00
abstract::Mineral metabolism in chronic kidney disease is attracting intense interest and unprecedented levels of research. The pharmaceutical industry has responded by developing various new agents. Bervoets et al. report the use of an unusual combination of basic-science techniques to increase understanding of the kinetics of...
journal_title:Kidney international
pub_type: 评论,杂志文章,评审
doi:10.1038/ki.2008.627
更新日期:2009-02-01 00:00:00
abstract:BACKGROUND:The benefit of the potent chemotherapeutic agent cisplatin in treating neoplasms is limited by nephrotoxicity. We tested the hypothesis that CD54 [intercellular adhesion molecule-1 (ICAM-1)] is an important mediator in cisplatin-mediated renal failure. METHODS:The effect of a monoclonal anti-CD54 antibody w...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00629.x
更新日期:1999-09-01 00:00:00
abstract::Hypoxia in the embryo is a frequent cause of intra-uterine growth retardation, low birth weight, and multiple organ defects. In the kidney, this can lead to low nephron endowment, predisposing to chronic kidney disease and arterial hypertension. A key component in cellular adaptation to hypoxia is the hypoxia-inducibl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.06.015
更新日期:2017-12-01 00:00:00
abstract::The inner medullary collecting duct (IMCD) is a major target site of atrial natriuretic peptide (ANP) for diuresis and natriuresis, and it is in a hypertonic condition made by the renal countercurrent multiplication system. We investigated the effects of hyperosmolality on ANP-stimulated cGMP generation in IMCD and gl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.178
更新日期:1994-05-01 00:00:00
abstract::Diabetic kidney disease is the leading cause of kidney failure. However, studies of molecular mechanisms of early kidney damage are lacking. Here we examined for possible linkage between transcriptional regulation and quantitative structural damage in early diabetic kidney disease in Pima Indians with type 2 diabetes....
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.08.013
更新日期:2018-02-01 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: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::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::We sought to study glomerular pathophysiology in a model of IgA nephropathy (IgAN). Preliminary experiments with oral immunization indicated that Lewis rats had higher IgA levels and IgA/IgG ratios than Wistar, Fischer or Sprague-Dawley rats. Six groups of Lewis rats were studied: four continuously orally immunized fo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.268
更新日期:1992-07-01 00:00:00
abstract::To examine whether hypoxia-inducible factor (HIF)-1α mediates the profibrotic effects of angiotensin II, we treated cultured renal medullary interstitial cells with angiotensin II and found that it increased HIF-1α levels. This was accompanied by a significant upregulation of collagen I/III, the tissue inhibitor of me...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.326
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND:The cardiovascular effects of angiotensin II are mediated by the angiotensin II type 1 receptor (AGT1R); one polymorphism of the AGT1R gene, A1166-->C, has been associated with hypertension. The hemodynamic response to angiotensin II is blunted in women compared to men, but interactions between gender, blood...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1046/j.1523-1755.2003.00867.x
更新日期:2003-04-01 00:00:00
abstract::Anti-NDP has been detected in the sera of 38 of 430 patients on regular hemodialysis at the Regional Kidney Disease Program in Minneapolis. It developed in these patients from 7 to 58 months after commencement of dialysis. Bacterial infection appeared temporally related to the development of anti-NDP in 12 patients. H...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1976.133
更新日期:1976-12-01 00:00:00
abstract::Autophagy is a conserved multistep pathway that degrades and recycles damaged organelles and macromolecules to maintain intracellular homeostasis. The autophagy pathway is upregulated under stress conditions including cell starvation, hypoxia, nutrient and growth-factor deprivation, endoplasmic reticulum stress, and o...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2015.11.021
更新日期:2016-04-01 00:00:00
abstract:BACKGROUND:Low dietary phosphorus (P) prevents parathyroid gland (PTG) hyperplasia and the development of secondary hyperparathyroidism (SH) in uremic rats. The present study explores the effects of P restriction on parathyroid hormone (PTH) synthesis and secretion and PT cell growth in rats with established SH and PTG...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00265.x
更新日期:2002-04-01 00:00:00
abstract::A substantial body of evidence has accumulated linking an increased incidence of cardiovascular disease in patients with acute kidney injury (AKI), chronic kidney disease (CKD), and end-stage renal disease (ESRD). A multitude of novel risk factors related to decreased kidney function might interact with the renal and ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2011.178
更新日期:2011-09-01 00:00:00
abstract::Anthropometric measurements and circulating growth factors were studied serially in 44 prepubertal children with growth failure and chronic renal failure (GFR = 10 to 40 ml/min/1.73 m2) who were randomized to receive either recombinant human growth hormone (rhGH; N = 30) or no treatment (N = 14). RhGH was given as Nut...
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.1997.268
更新日期:1997-06-01 00:00:00
abstract::The remnant kidney model was produced in mice by unilateral nephrectomy and partial infarction of the remaining kidney. Control mice underwent laparotomy only. The mice were studied for up to 44 weeks. No quantitative differences were noted in systolic arterial pressure, proteinuria, or histopathology between control ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00527.x
更新日期:1999-07-01 00:00:00
abstract::Arguably, no cell biology related to the loss of renal function is more debated than the ontogeny of fibrosis in the kidney. Recent studies suggest that the fibroblasts depositing most of the excess extracellular matrix in diseased kidneys derive from epithelial cells versus pericytes resident within the kidney. Reich...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2013.107
更新日期:2013-07-01 00:00:00
abstract::Accumulating evidence indicates that asymptomatic hyperuricemia is involved in the development of hypertension and chronic kidney disease. A 2-hit model has been proposed to explain the role of urate in hypertension. The first hit entails activation of the renin-angiotensin system and inhibition of nitric oxide synthe...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2020.05.056
更新日期:2020-11-01 00:00:00
abstract::Bone marrow (BM) cells are reported to contribute to the process of regeneration following myocardial infarction. The present study examined two independent clonal studies to determine the origin of bone marrow (BM)-derived cardiomyocytes. First, we transplanted single CD34(-)c-kit(+)Sca-1(+)lineage(-) side population...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1111/j.1523-1755.2005.00624.x
更新日期:2005-11-01 00:00:00
abstract::Genetic deletion of the adenosine A1 receptor (A1AR) increased renal injury following ischemia-reperfusion injury suggesting that receptor activation is protective in vivo. Here we tested this hypothesis by expressing the human-A(1)AR in A(1)AR knockout mice. Renal ischemia-reperfusion was induced in knockout mice 2 d...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.699
更新日期:2009-04-01 00:00:00
abstract::We studied binding and degradation of vasoactive intestinal peptide (VIP) by highly purified brush border and basolateral membranes from rabbit kidney cortex. Brush border and basolateral membranes were capable of 73 and 49% degradation of VIP after 20 minutes, and the degradation was totally prevented by bacitracin. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.32
更新日期:1991-02-01 00:00:00