Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to clarify the role of the renal renin-angiotensin system (RAS) in diabetic nephropathy (DN), which was induced by injection of streptozotocin (STZ). Male CBA/N and CBA/J mice were compared in this study. The former possesses a single renin gene, Ren1, whereas the latter carries two renin genes, Ren1 and Ren2. To examine the molecular dynamics of renal RAS, including renin, angiotensinogen (Agt), angiotensin-converting enzyme (Ace), angiotensin type 1 (Agtr1) and type 2 (Agtr2) receptors in experimental DN, we performed laser-microdissection (LMD) followed by reverse transcriptase nested polymerase chain reaction using each specific primer pairs and immunohistochemistry for renin and angiotensin II. CBA/N mice had a higher response after injection of STZ than CBA/J mice, showing a significant increase of the kidney/body weight ratio, although there was no significant difference between the two strains for the blood glucose level or pancreatic beta-cell response. The onset of renal pathological changes associated with DN was earlier and more severe in CBA/N mice than in CBA/J mice. Distinct immunoreactivities for renin and angiotensin II were newly distributed on the flattened epithelial cells in the dilated distal tubules in the cortex as well as the collecting ducts in the cortex and medulla, and were demonstrated more intensely in CBA/N mice than in CBA/J mice. Microdissectional analysis in both DN models revealed a higher incidence of RAS-related gene expression in CBA/J, Ren 1 Ren 2 mice than in CBA/N, Ren 1 mice. These findings suggest that intrarenal RAS plays an important role in the onset of renal pathological changes associated with DN. Additionally, Ren 1 mice have more severe histopathological nephropathy than Ren1 Ren2 mice, followed by marked production of angiotensin II.
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PMID:Upregulation of renal renin-angiotensin system in mouse diabetic nephropathy. 1619 Mar 18

We reported previously that various radiocontrast media cause apoptosis in porcine proximal tubular (LLC-PK(1)) cells, in which reduction in B-cell lymphoma (Bcl)-2 expression and caspase-3 activation are implicated. In the present study, we investigated a role for ceramide in radiocontrast media-induced apoptosis in renal tubular cells. LLC-PK(1) cells were exposed to radiocontrast media for 30 min, followed by incubation for 24 h in normal medium. Cell viability was assessed by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt assay, while apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling stain. Immunofluorescent stains were performed using antibodies against phosphorylated Akt (pAkt) and cAMP response element binding protein (CREB) (pCREB), and ceramide. The mRNA expression and protein content of Bcl-2 were determined by reverse transcriptase-polymerase chain reaction and enzyme immunoassay, respectively. In vivo model of contrast-induced renal injury was induced in mice with unilateral renal occlusion. The cell injury induced by the nonionic radiocontrast medium ioversol was reversed by inhibiting de novo ceramide synthesis with fumonisin B(1) (FB(1)) and L-cycloserine, but not by suppressing sphingomyelin breakdown with D609. FB(1) reversed ioversol-induced decrease in the immunoreactivities of pAkt and pCREB, reduction in Bcl-2 expression and caspase-3 activation. Like ioversol, C2 ceramide and the Akt inhibitor Src homology-6 induced apoptosis by reducing pAkt and pCREB-like immunoreactivities, lowering Bcl-2 expression and enhancing caspase-3 activity. Indeed, various radiocontrast media, excluding iodixanol which showed the least nephrotoxicity, enhanced ceramide-like immunoreactivity. The role for de novo ceramide synthesis was also shown in the in vivo model of radiocontrast nephropathy. We demonstrated here for the first time that the enhancement of de novo ceramide synthesis contributes to radiocontrast nephropathy.
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PMID:Involvement of de novo ceramide synthesis in radiocontrast-induced renal tubular cell injury. 1640 18

Loop diuretics are known to affect renal hemodynamics and possibly gene transcription, but the specific effect of furosemide on renal angiogenesis gene expression after acute ischemia is not known. We utilized an acute renal failure model in rats to test the hypothesis that furosemide improves renal hemodynamics and alters the transcriptional signature of acute ischemic nephropathy. Twenty-four male Sprague-Dawley rats were anesthetized by the intraperitoneal administration of 50 mg/kg urethane. Animals were divided into four groups (n = 6 each): (1) sham-operated group infused with saline; (2) sham-operated group infused with 30 microg/kg/hr furosemide (equivalent to a human dosage of 2 mg/hr); (3) unilateral renal ischemia (1 hr, left renal artery cross-clamping) followed by 6 hr of reperfusion; and (4) renal ischemia/ reperfusion (I/R) with furosemide. Renal artery blood flow (RBF), renal cortical perfusion (RCP), and renal corticomedullary tissue oxygen tension (PO2) were recorded throughout. Following 6 hr of reperfusion, left kidney RNA was used to probe microarrays. Gene expression was measured as percent positive control and confirmed using reverse transcriptase polymerase chain reaction. Physiologic data were analyzed by calculating area under the curve, and gene expression data were compared by using multiple analysis of variance with Tukey's post-hoc tests. Furosemide significantly increased RBF (P < 0.05) and PO2 (P < 0.05) in postischemic kidneys. Furosemide attenuated nine of the 13 ischemia-induced and 41 of 78 ischemia-suppressed angiogenesis-related genes. This attenuation was statistically significant (P < 0.05) for 17 I/R injury-suppressed genes. Data from this rat model of ischemic nephropathy suggest that furosemide improves renal hemodynamics and attenuates ischemia-related changes in gene expression.
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PMID:Effect of furosemide infusion on renal hemodynamics and angiogenesis gene expression in acute renal ischemia/reperfusion. 1652 16

Leukocyte infiltration, a hallmark of renal diseases, is orchestrated in part by the actions of chemokines. The chemokine CXCL8/interleukin (IL)-8 is expressed during renal diseases and allograft rejection, whereas the corresponding receptor CXCR1 has not been described previously. Expression of CXCR1 was characterized in peripheral blood using multicolor fluorescence-activated cell sorter analysis (FACS). CXCR1 was localized in 81 formalin-fixed, paraffin-embedded renal specimens by immunohistochemistry using a monoclonal antibody against human CXCR1. Included were biopsies with crescentic glomerulonephritis (CGN, n = 22), immunoglobulin (Ig) A nephropathy (n = 15), membranoproliferative glomerulonephritis (MPGN, n = 17), lupus nephritis (n = 12), membranous nephropathy (n = 11), and non-involved parts of tumor nephrectomies (n = 4). Consecutive tissue sections of human tonsils, allograft explants, and renal biopsies were stained for CD15- and CD68-positive cells. Expression of CXCR1 and CXCL8/IL-8 mRNA was quantified by real-time reverse transcriptase-polymerse chain reaction of microdissected renal biopsies (n = 35) of the same disease entities. By FACS CXCR1 expression was found on polymorphonuclear CXCR1 expression by polymorphonuclear leukocytes (PMNs), natural killer cells, and a subpopulation of monocytes. By immunohistochemistry, CXCR1 expression was found on infiltrating inflammatory cells (predominantly PMNs), as well as on intrinsic renal cells (arterial smooth muscle cells, endothelial cells of peritubular capillaries). The distribution pattern of CXCR1 differed between disease entities. The highest numbers of glomerular CXCR1-positive cells were present in biopsies with MPGN, followed by lupus nephritis, and CGN. CXCR1 might be involved in the recruitment of PMNs to the glomerular tuft, which could be targeted by CXCR1-blocking agents.
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PMID:Expression of the chemokine receptor CXCR1 in human glomerular diseases. 1654 Oct 17

Acute rejection (AR) is a dominant risk factor for developing chronic allograft nephropathy (CAN) after kidney transplantation. CAN is characterized by progressive interstitial fibrosis. It has been associated with increased transforming growth factor (TGF)-beta1 expression, however, kinetic studies are absent. We investigated whether intragraft TGF-beta1 expression in various causes of early graft dysfunction may influence late renal allograft dysfunction. A total of 174 human renal biopsies were quantified for TGF-beta1 mRNA expression using real-time reverse transcriptase-polymerase chain reaction. Expression levels were correlated with the Banff histopathological grades, TGF-beta1 immunohistology, and clinical follow-up. TGF-beta1 was most markedly upregulated in AR, CAN, and acute tubular necrosis - delayed graft function compared to non-rejecting controls (P < 0.001). TGF-beta1 expression was heightened in borderline changes (P < 0.01), recurrence of glomerulonephritis, and cyclosporine toxicity (P < 0.05). There was no correlation between intragraft TGF-beta1 expression during AR and short-term outcome of a rejection episode. TGF-beta1 gene overexpression during CAN has been shown to be associated with the increased risk for renal allograft dysfunction 18 months after biopsy (odds ratios 9.9 vs 3.2, respectively). Intragraft TGF-beta1 mRNA expression is significantly upregulated in both AR and CAN. Thus, our results support the hypothesis that TGF-beta1 might play a key role in chronic allograft dysfunction.
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PMID:TGF-beta1 mRNA upregulation influences chronic renal allograft dysfunction. 1661 32

Since 1984, human immunodeficiency virus-associated nephropathy has been established as a clinical entity that presents with nephrotic syndrome and progressive kidney failure. The pathological description is usually consistent with a collapsing form of focal segmental glomerulosclerosis. Podocytes and renal tubular cells have been proposed as a reservoir for the human immunodeficiency virus. This nephropathy is the third leading cause of end-stage renal disease in the population of African descent. It is documented that highly active antiretroviral therapy (HAART) successfully reverses or at least controls nephropathy in HIV-positive patients. The success of the treatment of HIV nephropathy now poses 2 problems to nephrologists: (1) an increased population of HIV-positive patients with chronic kidney disease not yet on dialysis and (2) potential nephrotoxicity of antiretroviral medications as well as medications used to treat opportunistic infections. HAART is defined by the combination of 2 reverse transcriptase inhibitors with a protease inhibitor or 3 reverse-transcriptase inhibitors. Many of these antiretrovirals have well-defined nephrotoxic effects. The objective of this text is to review data pertaining to some of the most common antiretrovirals (ARTs) and include information regarding nephrotoxicity of the medications frequently used to combat opportunistic infections. ARTs included in the review are (1) nucleoside reverse-transcriptase inhibitors (zidovudine and didanosine), (2) nucleotide reverse transcriptase inhibitors (adefovir and tenofovir), (3) the protease inhibitors (indinavir and saquinavir), and (4) the HIV fusion inhibitors.
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PMID:Nephrotoxicity as a complication of antiretroviral therapy. 1681 36

In chronic renal disease, the progressive accumulation of collagen and other extracellular matrix proteins in the mesangium results in fibrosis, glomerulosclerosis, and eventual renal failure. Mice deficient in proalpha2(I) collagen are not only a model of osteogenesis imperfecta but also accumulate fibrillar homotrimeric type I collagen in the mesangium. This accumulation spreads to the subendothelial space in the peripheral capillary loops. Picosirius red staining of kidney sections demonstrates that in comparison to wild-type mice, Col1a2-deficient homozygous and heterozygous mice exhibit abnormal glomerular collagen deposition in a gene dosage-dependent manner. The glomerulopathy initiates during the first postnatal week, appears progressive following the pattern of glomerular maturation and results in albuminuria in severely affected animals. In situ hybridization revealed no gross differences in steady-state proalpha1(I) and proalpha2(I) collagen mRNA levels among the three genotypes. Quantitative reverse transcriptase-polymerase chain reaction, however, using whole kidney sections showed a twofold increase in steady-state proalpha1(I) collagen mRNA in 1-month homozygous Col1a2-deficient animals compared with wild-type and heterozygous animals. We suggest that glomerular collagen deposition seen in the osteogenesis imperfecta model mice is, in part, owing to pretranslational mechanisms and may represent an over compensation of wound healing.
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PMID:Type I collagen glomerulopathy: postnatal collagen deposition follows glomerular maturation. 1736 Nov 18

To evaluate tenofovir-related nephropathy, we quantified calculated glomerular filtration rates (GFR) and renal tubular function in 46 tenofovir-treated patients and 25 without tenofovir. We also analysed patients who stopped tenofovir for drug-related nephrotoxicity at our clinic. Tenofovir use combined with non-nucleoside reverse transcriptase inhibitors, but not with protease inhibitors, resulted in a significant increase in calculated GFR. Tenofovir use was associated with significantly lower phosphatemia and a marginally increased fractional excretion of uric acid, but no other signs of tubulopathy.
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PMID:Effect of tenofovir on renal glomerular and tubular function. 1758 97

Tenofovir is an acyclic nucleotide analogue reverse transcriptase inhibitor that is commonly prescribed as part of a highly active antiretroviral therapy (HAART) regimen in HIV-infected patients. Although it is generally well tolerated, renal insufficiency has been associated with its use. We report a biopsy-proven case of acute renal failure that developed within weeks of initiating a HAART regimen containing tenofovir, and review the literature with specific attention to cases of renal failure occurring within 8 weeks of tenofovir initiation. Our patient developed renal insufficiency within 3 weeks of initiating tenofovir-containing HAART and overt renal failure was noted within 5 weeks. Renal biopsy demonstrated histopathologic changes suggestive of HIV nephropathy, despite normal baseline serum creatinine values. Thirty additional cases of tenofovir-associated renal failure have been reported. In the majority (n = 22, 73%), renal failure occurred months after initiating therapy (range: 5-26 months). However, in a significant subset (n = 8, 27%), renal failure occurred within 8 weeks of treatment initiation. Our data suggest that some patients are at risk for developing renal failure within weeks of tenofovir initiation. Thorough evaluation of renal function should be undertaken before prescription of tenofovir-containing HAART. For those in whom subclinical renal disease is discerned, added vigilance when monitoring renal function may be warranted.
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PMID:Early onset of tenofovir-induced renal failure: case report and review of the literature. 1766 Aug 85

Puberty unmasks or accelerates the nephropathy of diabetes mellitus (DM). We performed focused microarray analysis to test the hypothesis that one or more genes in the transforming growth factor beta (TGF-beta) signaling system would be differentially regulated in male rats depending on their age at onset of DM. Littermates were started on the 6-week protocol at 4 weeks or 14 weeks of age. Renal cortical RNA was isolated and analyzed using gene chips with more than 30,000 transcripts. Age-specific effects of DM were demonstrated for 1,760 transcripts. Analysis then focused on 89 genes involved in the TGF-beta signaling pathway. Three of these genes showed age-dependent responses to DM, confirmed by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Connective tissue growth factor (CTGF) mRNA and protein were both increased approximately 30% in the renal cortex 6 weeks after adult-onset DM, with no alteration in either parameter after juvenile onset. Follistatin and avian myelocytomatosis viral oncogene homolog mRNA both showed a similar age-related pattern of response to DM, but protein levels did not parallel mRNA for either of these gene products. Given the known roles of CTGF in progressive nephropathies, it is an attractive candidate to explain pubertal acceleration or unmasking of the kidney disease of diabetes.
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PMID:Prepubertal onset of diabetes prevents expression of renal cortical connective tissue growth factor. 1803 May 1


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