Experimental nephrology最新文献

{"title":"Gene regulation of atrial natriuretic peptide A, B, and C receptors in rat glomeruli.","authors":"K Itoh,&nbsp;H Nonoguchi,&nbsp;N Shiraishi,&nbsp;K Tomita","doi":"10.1159/000020621","DOIUrl":"https://doi.org/10.1159/000020621","url":null,"abstract":"<p><strong>Background and methods: </strong>Atrial natriuretic peptide (ANP) has three types of receptor. We investigated the gene regulation of three types of ANP receptors (ANPR-A, B, and C) in rat glomeruli using reverse transcription coupled with competitive polymerase chain reaction (PCR).</p><p><strong>Results: </strong>Competitive PCR revealed that ANPR-C mRNA expression was most abundant (ANPR-C > A >> B) in glomeruli from control rats among mRNA expressions of three receptors, which were 20- to 15,000-fold higher than those in inner medullary collecting ducts. Two days' dehydration caused reversible decreases of ANPR-A, B, and C mRNAs by 50-80%. To determine the mechanisms of down-regulation of mRNA expression, isolated glomeruli were incubated in isotonic or hypertonic solution. Hyperosmolality induced by NaCl, mannitol or raffinose caused significant increases of ANPR-A, B, and C mRNA expression. Hypertonicity by urea showed smaller effects. ANP stimulated the expression of ANPR-A, B, and C mRNA in vitro.</p><p><strong>Conclusion: </strong>These results indicate that dehydration caused reversible decreases of ANPR-A, B, and C mRNA expression in glomeruli, and these decreases were not caused by increased plasma osmolality but probably by lower circulating levels of ANP.</p>","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1999-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000020621","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21314088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L-Histidinol attenuates Fanconi syndrome induced by ifosfamide in rats.","authors":"O A Badary","doi":"10.1159/000020620","DOIUrl":"https://doi.org/10.1159/000020620","url":null,"abstract":"<p><p>The effect of L-histidinol (LHL), a structural analogue of the essential amino acid L-histidine, on ifosfamide (IFO) induced nephrotoxicity was investigated in the rat. The aim of this study was to assess whether oral supplementation of LHL could attenuate Fanconi syndrome (FS) induced by IFO. Male Wistar albino rats received daily injections of IFO (50 mg/kg) for 5 days with or without oral supplementation of 0.5% LHL in the drinking water. LHL was supplemented for 3 days before IFO administration and daily thereafter. Control rats were injected with saline with or without oral LHL. The results demonstrated that IFO induces a FS characterized by wasting of glucose, electrolytes, and organic acids, along with elevated serum creatinine and urea levels and decreased creatinine clearance. IFO-induced FS was associated with significant renal nonprotein sulfhydryl depletion and lipid peroxide (malondialdehyde) accumulation. LHL strongly ameliorated the severity of renal dysfunction induced by IFO, with significant decreases in total and fractional excretions of Na(+), K(+), PO(4)(3-), and glucose. Also, LHL significantly decreased the elevated serum creatinine and urea levels and significantly increased the creatinine clearance. Moreover, the beneficial effects of LHL were associated with a significant improvement of IFO-induced nonprotein sufhydry depletion and lipid peroxide accumulation. These results demonstrate that oral supplementation of LHL can partially protect against IFO-induced FS in rats.</p>","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1999-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000020620","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21315473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of dopamine-induced natriuresisby the dopamine-metabolizing enzyme catechol-O-methyltransferase.","authors":"C Odlind,&nbsp;V Göransson,&nbsp;I Reenilä,&nbsp;P Hansell","doi":"10.1159/000020619","DOIUrl":"https://doi.org/10.1159/000020619","url":null,"abstract":"<p><p>Dopamine (DA) is an intrarenal natriuretic hormone involved in sodium homeostasis. A study was performed to elucidate two possible regulatory pathways of DA-induced natriuresis, i.e., metabolism and precursor delivery. This was done by use of an intraperitoneal injection of a catechol-O-methyltransferase (COMT) inhibitor, entacapone, or intravenous infusion of the DA precursor, L-dopa. Entacapone (30 mg/kg i.p.) induced a more than fivefold increase in renal sodium excretion which occurred without changes in renal haemodynamics. The natriuretic response was highly dependent on DA D(1)-like receptor activation, since the selective D(1)-like receptor antagonist SCH23390 attenuated the natriuretic response by 61%, while the selective D(2)-like receptor antagonist sulpiride was ineffective. The urinary excretion of DA did not increase. Infusion of L-dopa (60 microg/h/kg) only induced a twofold increase in sodium excretion, but the urinary excretion of DA increased more than 17-fold. The L-dopa-induced natriuretic response occurred without increments in glomerular filtration rate and could be blocked with the D(1)-like receptor antagonist SCH23390. It is concluded that the DA-metabolizing enzyme COMT is involved in the regulation of the natriuretic effect of intrarenal DA. It may be speculated that intrarenal DA activity is not primarily determined on the basis of delivered precursor, but on that of the level of DA metabolism.</p>","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1999-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000020619","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21314084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear protein transport pathways.","authors":"M Köhler,&nbsp;H Haller,&nbsp;E Hartmann","doi":"10.1159/000020616","DOIUrl":"https://doi.org/10.1159/000020616","url":null,"abstract":"<p><p>Nuclear proteins like transcription factors and ribosomal proteins are synthesized in the cytoplasm and have to be transported into the nucleus to fulfill their functions. The transport of proteins >20-60 kD through the nuclear pore complex (NPC) into the nucleus is an active, energy-requiring process. Transport substrates are recognized by their transport proteins via certain signals. The best-characterized protein import pathway is the 'classical' nuclear localization signal-dependent pathway with importin alpha and beta carrying the substrate to the NPC. The transport of the importin-substrate complex into the nucleus is regulated by the small GTPase Ran/TC4. During the last years more than ten proteins have been discovered which have already been proven or are very likely to be nuclear transport factors of distinct import pathways: members of the importin alpha protein family are very similar and transport in complex with importin beta nuclear localization signal-bearing proteins into the nucleus. Members of the Ran-binding protein family show some weak similarity to importin beta. Sharing a common domain at the amino terminus, they are able to bind RanGTP, a prerequisite for their function as nuclear import or export factors for distinct proteins or RNAs. However, Ran/TC4 seems to play a key regulatory role in all nuclear transport pathways described so far, although the molecular mechanism of the translocation step through the NPC is still unclear.</p>","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1999-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000020616","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21315470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transdifferentiation of distal but not proximal tubular epithelial cells from human kidney in culture.","authors":"P C Baer,&nbsp;U W Tunn,&nbsp;G Nunez,&nbsp;J E Scherberich,&nbsp;H Geiger","doi":"10.1159/000020618","DOIUrl":"https://doi.org/10.1159/000020618","url":null,"abstract":"<p><p>Human renal proximal and distal (thick ascending limb and early distal convoluted tubule) epithelial cells have been isolated according to their specific antigen expression. The cells were well characterized by flow cytometry, enzyme cytochemistry and electron microscopy and cultured for up to 3 months. Cultured tubular cells coexpressed cytokeratin and vimentin as intermediate filament proteins. While primary isolated cells, proximal as well as distal, revealed the phenotypic characteristics of their nephron origin, cultured distal cells showed the tendency to dedifferentiate/transdifferentiate. Distal cells lost their characteristic expression of Tamm-Horsfall glycoprotein and started de novo expression of the proximal marker proteins aminopeptidase M, gamma-glutamyl transferase and dipeptidyl peptidase IV. The expression of these antigens by distal cells could be shown by flow-cytometric analysis and fluorescence microscopy. Enzyme activity assays revealed the activity of aminopeptidase M, gamma-glutamyl transferase and dipeptidyl peptidase IV, but not of the proximal marker enzyme alkaline phosphatase. This antigenic shift could not be prevented in different culture media, and the original phenotype could not be restored. Cultured cells displayed characteristic hormonal stimulation patterns indicative of their proximal and distal origins, as shown by activation of adenylate cyclase by different peptide hormones. These results indicate that distal tubular cells possibly transdifferentiate to a more proximal phenotype in view of loss of the distal marker enzyme Tamm-Horsfall protein and de novo expression of proximal marker enzymes like dipeptidyl peptidase IV and aminopeptidase M.</p>","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1999-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000020618","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21315471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transfer of genetically engineered cells to the glomerulus.","authors":"M Kitamura","doi":"10.1159/000020611","DOIUrl":"https://doi.org/10.1159/000020611","url":null,"abstract":"<p><p>In the rat, cultured cells injected into the renal circulation are entrapped in the glomerulus. This peculiar property allows to create chimeric glomeruli in which genetically engineered cells are populated. Using glomerular cells engineered in vitro, it is feasible to generate glomeruli that produce recombinant gene products. This approach would be useful for identification of local function of a certain gene product in the glomerulus and for therapeutic intervention in glomerular disease. Transfer of activated leukocytes to the glomerulus is useful to elucidate pathologic actions of infiltrating cells on the glomerular structure and function. Use of leukocytes in which certain gene function is selectively reinforced or deleted should enable to disclose exact roles of leukocyte-associated genes in glomerular pathophysiology. Transfer of engineered leukocytes also allows to investigate how resident cells modulate the activity of infiltrating cells in normal and pathologic circumstances. This article summarizes current experience with adoptive transfer of engineered cells to the glomerulus and addresses its potential application to kidney research.</p>","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1999-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000020611","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21220932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of human natural xenoantibody depletion and complement inactivation on early pig kidney function.","authors":"J M Cruzado,&nbsp;J Torras,&nbsp;M Riera,&nbsp;E Condom,&nbsp;N Lloberas,&nbsp;I Herrero,&nbsp;J Martorell,&nbsp;J M Grinyó","doi":"10.1159/000020605","DOIUrl":"https://doi.org/10.1159/000020605","url":null,"abstract":"<p><p>Preformed xenoreactive natural antibodies (XNA) and complement mediate hyperacute xenograft rejection (HXR) in pig-to-human discordant xenotransplantation. In a pig kidney-human blood xenoperfusion model, we investigated whether XNA depletion and/or human complement inactivation preserved early pig kidney function. Pig kidneys were perfused for 180 min with pig blood (AUTO group, n = 8), human blood (HETER group, n = 6), complement-inactivated human blood (COMi group, n = 5), XNA-depleted human blood (ABd group, n = 5) or complement-inactivated and XNA-depleted human blood (ABd&COMi group, n = 5). HETER kidneys were rejected after 15-30 min and showed vascular microthrombi and interstitial hemorrhages. XNA depletion and/or complement inactivation prevented HXR. The glomerular filtration rate in ABd, COMi and ABd&COMi groups was significantly lower than in the AUTO group. Also, beyond 60 min, the COMi group showed a significantly lower glomerular filtration rate than that observed in ABd and ABd&COMi groups. Kidneys from ABd, COMi and ABd&COMi groups displayed endothelial cell edema, as well as higher soluble P-selectin levels and a higher renal myeloperoxidase content than the AUTO group kidneys. COMi and ABd&COMi groups had a significantly lower renal myeloperoxidase level than the HETER group. Also, in contrast to HETER and ABd groups, these complement-inactivated groups failed to show a positive correlation between P-selectin and renal myeloperoxidase. We also investigated platelet-activating factor (PAF) as possible mediator for these functional and pathologic changes. We found that blood PAF levels were similar in HETER, ABd, COMi and ABd&COMi groups and significantly higher than in the AUTO group. Also, when PAF was added to porcine endothelial cell monolayers, morphological changes due to cytoskeleton contraction were observed, and these changes were prevented by preincubation with a PAF receptor antagonist. In conclusion, although depletion of XNA and/or complement inactivation prevent HXR, the pig kidney function is not preserved at the level of the autologous combination. The PAF overproduction observed in the xenogenic combination, which is independent of the presence of XNA and complement, may be, at least in part, responsible for early endothelial cell morphological changes still present when HXR is prevented.</p>","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1999-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000020605","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21220968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell cycle regulatory proteins in glomerular disease.","authors":"S J Shankland,&nbsp;M Al'Douahji","doi":"10.1159/000020603","DOIUrl":"https://doi.org/10.1159/000020603","url":null,"abstract":"<p><p>The growth response of resident glomerular cells is determined by the underlying disease. Thus glomerular cells can proliferate, fail to proliferate, hypertrophy or apoptose. Cell growth is controlled by cell cycle regulatory proteins, and cell proliferation requires that cyclin-dependent kinases (CDK) be activated by partner cyclins. Inhibiting CDK2 reduces mesangial cell proliferation. Mesangial cell proliferation also requires that levels of specific cyclin kinase inhibitors (CKI) decrease. In contrast, the visceral glomerular epithelial cells' inability to proliferate may be due to increased levels of CKI. Moreover it is becoming increasingly clear that mesangial cell hypertrophy in diabetes requires increased CKI expression. Finally, apoptosis, which is often linked to proliferation, may also be due to the increased activity of CDK2. Thus, identifying specific cell cycle regulatory proteins following injury may provide future targets for therapy in glomerular disease.</p>","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1999-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000020603","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21221028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of erythrocyte aminolevulinate dehydratase by a 56.2-kD peptide from uremic plasma.","authors":"M Guolo,&nbsp;C Machalinski,&nbsp;M Biscoglio,&nbsp;A M Stella,&nbsp;C Franco,&nbsp;L Pataro,&nbsp;R E de Salamanca,&nbsp;A Batlle","doi":"10.1159/000020607","DOIUrl":"https://doi.org/10.1159/000020607","url":null,"abstract":"<p><p>Among the abnormalities in erythrocyte porphyrin metabolism already described in patients with chronic renal failure on hemodialysis, a decrease in blood aminolevulinate dehydratase activity has been reported, suggesting the presence in uremic plasma of an inhibitor of the enzyme. The aim of this work has been to isolate and characterize such an inhibitor. Blood samples from 105 patients with chronic uremia were collected; plasma was applied to Sephadex G-100 columns and the fraction with the highest inhibiting capacity was identified and purified by subsequent SDS-polyacrylamide gel electrophoresis, followed by electroelution and electroblotting. It was demonstrated that the factor present in plasma of uremic patients inhibited blood aminolevulinate dehydratase in a concentration-dependent manner; its inhibitory properties were abolished after heat, trypsin and TCA treatment indicating its peptidic nature. The purified inhibitor has an apparent molecular mass of 56.2 kD, it inhibits blood aminolevulinate dehydratase in a competitive way and the Ki value is 12x10(-6) M. The amino acid composition of the inhibitor has been determined and it has been found that its N-terminal amino acid is blocked. The isolated peptide may play a role in heme biosynthesis disturbances and in the pathogenesis of uremic anemia.</p>","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1999-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000020607","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21220970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of the ROMK potassium channel in the kidney.","authors":"H Wald","doi":"10.1159/000020602","DOIUrl":"https://doi.org/10.1159/000020602","url":null,"abstract":"<p><p>ROMK is a gene encoding inwardly rectifying adenosine triphosphate regulated K+ channels. Alternative splicing of ROMK exons yields several different transcripts, ROMK 1-3, that are differentially expressed along the nephron. Cloned ROMK channels expressed in Xenopus oocytes exhibit properties similar to those of the native low-conductance K+ secretory channels in cortical collecting duct and medullary thick ascending limb, as manifested by use of the patch-clamp technique. These similarities between the cloned and native channels suggest that ROMK represents the low-conductance secretory K+ channels in the kidney. We studied the role of dietary K+ and aldosterone in the regulation of ROMK mRNA expression in the rat kidney. K+ deficiency downregulated ROMK mRNA in cortex and medulla. Adrenalectomy markedly downregulated cortical ROMK, while it increased it in the medulla. In adrenalectomized rats K+ deficiency decreased ROMK mRNA in cortex and medulla similarly to intact rats. Na-K-ATPase subunits alpha1 and beta1 were regulated in parallel to the regulation of ROMK. In the medulla ROMK mRNA correlated highly with serum K+ and with the alpha1 and beta1 subunits of Na-K-ATPase. These results show that cortical ROMK expression is regulated by aldosterone and K+, while the medullary ROMK mRNA is regulated by serum K+, irrespective of aldosterone.</p>","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1999-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000020602","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21221027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}