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:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the activity of some enzymes of the transcriptive DNA system to assess lymphocyte metabolic potential in patients with proliferative glomerulopathies. This study included analysis of the activity of three classes DNA-dependent RNA polymerases, before and 6 months after immunosuppressive therapy (Azathioprine + Prednisone). The enzyme activity was measured in nuclear extracts of T and B lymphocytes by estimation of the uptake of 3/H/UTP in the presence of alpha-amanitine. The immunoblotting technique using anti-polymerase I antibodies and nuclear proteins separation with immobilized exogenous DNA were employed to assess a type of the increase of the DNA-dependent RNA polymerase activity in lymphocytes populations (enhancement of the synthesis or limited depolymerization and degradation of the active enzyme). We found that the RNA polymerizing activity was increased in both lymphocyte populations. In T lymphocytes the increase was caused by an enhanced activity of transcript DNA enzymes, secondary to increased gene expression. In B lymphocytes an increase in enzyme activity was rather due to large stability RNA-polymerases in these cells. DNA-dependent RNA polymerase I in T and B cells was not modified by immunosuppression, while reduction in enzymatic activity of the remaining RNA-polymerase classes in T lymphocytes depends on partial limitation of their gene expression. Our study indicates that profound and various lymphocyte metabolic changes occur in patients with proliferative glomerulonephritis resulting from modifications in a gene expression and initiation of DNA synthesis in these cells.
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PMID:Proliferative glomerulonephritis and the activity of lymphocyte DNA transcriptional enzymes. 182 13

We report a woman with systemic lupus erythematosus (SLE) with diffuse proliferative glomerulonephritis and anti-dsDNA antibodies whose serum contained autoantibodies specific for the phosphorylated form of RNA polymerase II (RNAP IIO), Su and ribosomal P antigen, as well as anti-topoisomerase I antibodies, a marker for scleroderma (SSc). Over 6 years, the patient exhibited clinical manifestations consistent with SLE without clinical evidence of scleroderma. The reactivity of her serum autoantibodies with the phosphoproteins ribosomal P, topoisomerase I, and RNAP IIO is consistent with recognition of autoepitopes comprised in part of phosphate groups. This may explain the unexpected coexistence of marker autoantibodies for SLE and scleroderma, possibly with implications for the mechanisms of autoantibody generation.
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PMID:Autoantibodies to topoisomerase I in a patient with systemic lupus erythematosus without features of scleroderma. 852 30

We have previously shown in inbred strains of mice which naturally develop systemic lupus erythematosus that kidney C3, C2, C4 and factor B gene expression increases coincidently with the occurrence of glomerulonephritis, suggesting that local tissue complement gene expression could contribute to the pathogenesis of immune complex injury. In this study, we investigated the synthesis of complement proteins in glomerular epithelial cells (GECs) and its regulation. Using biosynthetic labelling, immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we demonstrated that GECs synthesized C1r, C1s, C1 inhibitor, C3, C2 and factor B. Interferon-gamma induced increases in the synthesis of all these proteins. Both factor B and C3 proteins were increased following addition of either IL-1beta, IL-6 or TNF-alpha to GEC cultures; however, these cytokines did not increase either C2, C1r, C1s or C1-inhibitor biosynthesis. Lipopolysaccharide affected the biosynthesis of these proteins in a similar way. A semiquantitative analysis of the mRNA expression of some of these proteins by reverse-transcriptase polymerase chain reaction showed that these cytokine effects were pretranslational as there was enhancement of factor B mRNA expression by IL-1, TNF-alpha, IFN-gamma, IL-6 and endotoxin, but only IFN-gamma enhanced C1-inhibitor and C4 mRNA expression. These results may be of significance in the immunopathogenesis of glomerulonephritis, where it is likely that local complement production in GECs is independently regulated by cytokines, derived from resident glomerular mesangial cells or infiltrating monocyte/macrophages and T cells.
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PMID:Differential cytokine regulation of complement proteins in human glomerular epithelial cells. 922 27

A reciprocal regulation between the expression of tumor necrosis factor (TNF)-alpha and interleukin (IL)-10, demonstrated in monocytes and mesangial cells, provides a rationale for new therapeutic approaches in glomerulonephritis (GN). Administration of IL-10 to mice with antibody-mediated GN attenuated the severity of glomerular lesions. Recently, however, it has been shown that the genetically determined predominance of Th1 or Th2 cytokines results in different glomerular responses to the same planted antigen, but in an equally severe impairment of renal function. We looked for the expression of IL-10 and TNF-alpha in 111 renal biopsy specimens with proliferative and nonproliferative forms of GN and in 10 control kidneys, by means of immunocytochemistry, in situ hybridization, or reverse-transcriptase polymerase chain reaction (RT-PCR). Six patients had acute endocapillary GN (AGN), 10 patients had pauci-immune GN due to microscopic polyangiitis (MP), 48 patients had immunoglobulin-A (IgA)-GN, 18 patients had idiopathic membranous GN (IMGN), 12 patients had minimal change disease (MCD), and 13 patients had focal segmental glomerulosclerosis (FSGS) and four other forms of GN. Antibodies against monocytes (CD14) and macrophages (CD68) were applied to attribute the expression of TNF-alpha and IL-10 to resident renal or infiltrating cells. We show that mRNAs for TNF-alpha and IL-10 are detected by RT-PCR and in situ hybridization in the normal kidney. A constitutive expression of TNF-alpha protein is observed in mesangial cells, smooth muscle cells in renal arteries, and in the interstitium. A trace immunoreactivity for IL-10 is restricted to arterial smooth muscle cells, distal tubular epithelial cells, and some interstitial cells. Upregulation of both cytokines is found in glomerular diseases. The expression of TNF-alpha increases in mesangial areas in MCD, IMGN stages I/II, and IgA-GN with minor glomerular abnormalities, that is, under conditions with a generally well-preserved glomerular structure. Conversely, marked glomerular proliferation in IgA-GN and, particularly, acute vascular lesions in MP, are accompanied by a significant upregulation of IL-10 (at the mRNA and protein level). Patients with nephrotic-range proteinuria show a significant increase in tubulointerstitial expression of IL-10, whereas the immunoreactivity for TNF-alpha reflects the extent of interstitial fibrosis. Thus, our results confirm previous suggestions that proinflammatory and antiinflammatory cytokines are produced in situ by resident renal cells and contribute to the natural course of human GN.
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PMID:In situ upregulation of IL-10 reflects the activity of human glomerulonephritides. 966 28

Membranous nephropathy, mesangial proliferative glomerulonephritis and renal amyloidosis are common renal pathology in RA patients. However, IgA nephropathy and diffuse thinning of glomerular basement membrane are described as common and characteristic renal lesions in Japanese RA patients. Glomerular filtration rate may decrease significantly in active lupus nephritis, but renal plasma flow does not change or even increase. These findings seem to be characteristic of SLE patients with active renal disorders. Therefore, filtration fraction may be a useful clinical parameter to evaluate SLE patients. Scleroderma renal crisis(SRC) has been believed to be the most serious renal disorder in systemic sclerosis (SSc). Recently, the presence of an antibody to RNA polymerase has been associated with a high prevalence of SRC.
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PMID:[Renal disorders in patients with collagen vascular diseases]. 1007 13

A 24-year-old woman with overlapping features of sclerodermia sine scleroderma and systemic lupus erythematosus (SLE) presented with rapidly accelerating hypertension accompanied by neuropsychological deficits and tonic-clonic seizures. Kidney biopsy showed severe intimal hyperplasia of small renal arteries but no glomerulonephritis. Following treatment with ACE inhibitor, prednisolone and cyclophosphamide complete remission was achieved with minimal brain damage and normal kidney function. Anti-RNA polymerase I, II and III antibodies have remained positive during follow-up for 2 years, suggesting a linkage with the underlying pathogenetic pathway.
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PMID:Renal crisis in asclerodermic scleroderma--lupus overlap syndrome. 1178 81

The hepatitis C virus (HCV) is a small enveloped RNA virus belonging to the family flaviviridae and genus hepacivirus. The HCV RNA genome is 9,600 nucleotides in length and encodes a single polyprotein that is post-translationally cleaved into 10 polypeptides including t3 structural (C, E1, and E2) and multiple nonstructural proteins ([NS] NS2 to NS5). The NS proteins include enzymes necessary for protein processing (proteases) and viral replication (RNA polymerase). The virus replicates at a high rate in the liver and has marked sequence heterogeneity. There are 6 genotypes and more than 90 subtypes of HCV, the most common in the United States being 1a and 1b (approximately 75%), 2a and 2b (approximately 15%), and 3 (approximately 7%). Acute hepatitis C is marked by appearance of HCV RNA in serum within 1 to 2 weeks of exposure followed by serum alanine aminotransferase (ALT) elevations, and then symptoms and jaundice. Antibody to HCV (anti-HCV) tends to arise late. In acute resolving hepatitis, HCV RNA is cleared and serum ALT levels fall to normal. However, 55% to 85% of patients do not clear virus, but develop chronic hepatitis C. Chronic hepatitis C is often asymptomatic, but is usually associated with persistent or fluctuating elevations in ALT levels. The chronic sequelae of hepatitis C include progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Extra-hepatic manifestations include sicca syndrome, cryoglobulinemia, glomerulonephritis, and porphyria cutanea tarda. Knowledge of the course and outcome of hepatitis C is important in developing approaches to management and therapy.
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PMID:Course and outcome of hepatitis C. 1240 73

Essential mixed cryoglobulinemia (type II) has turned out to be secondary to hepatitis C virus (HCV) infection in the large majority of patients. Interferon might be anticipated to be effective only in HCV-associated cryoglobulinemias. We found that interferon was highly effective in an HCV-positive patient with true essential type II mixed cryoglobulinemia. The patient presented with symptomatic cryoglobulinemic vasculitis without underlying immunologic, infectious, or neoplastic diseases. Tests for HCV viremia, a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, and anti-HCV antibodies (third-generation assays) were positive before therapy. The patient had severe cryoglobulinemic vasculitis with purpura, peripheral neuropathy, and membranous proliferative glomerulonephritis. The cryocrit before therapy was 6 percent in the patient. Recombinant interferon alfa-2a (Roferon-A, Hoffmann-LaRoche, Basel, Switzerland) was administered at a dose of 3 million units per day for three months and 3 million units every other day for the subsequent nine months, a protocol adopted for HCV-associated cryoglobulinemia. The patient had a complete clinical response, with the disappearance of serum cryoglobulins and all signs of cutaneous vasculitis and with the normalization of kidney-function results and urinary values in the patient with nephropathy. The patient has remained in complete remission for more than one year since the withdrawal of therapy. True essential mixed cryoglobulinemia with HCV infection complicated with glomerulonephritis represents a therapeutic challenge.
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PMID:Hepatitis C virus-associated type II mixed cryoglobulinemia vasculitis complicated with membranous proliferative glomerulonephritis. 1921 13

B6.MRLc1(82-100) congenic mice carrying the telomeric region of lupus-prone MRL chromosome 1 develop autoimmune glomerulonephritis (GN). The GN susceptibility locus of B6.MRLc1(82-100) contains the interferon activated gene 200 (Ifi200) family, which consists of Ifi202, 203, 204, and 205. Recently, Ifi202 was suggested as a candidate gene for murine lupus. In this study, we assessed the association between Ifi200 family and GN in several disease models. We compared the expression of Ifi200 family members in 24 organs between the C57BL/6 and B6.MRLc1(82-100). The expressions of Ifi200 family members differed between strains, and the most dramatic differences appeared in Ifi202 expression. Briefly, in the blood, immune organs, lungs, and testes mRNA expression was higher in B6.MRLc1(82-100) mice. In the kidney and immune organs, only Ifi202 expression increased with the development of GN in B6.MRLc1(82-100), and significant differences from C57BL/6 were observed even before disease onset. Ifi202 expression in the kidneys of BXSB, NZB/WF1, and MRL/lpr was also significantly high in the early- and late-disease stages. Furthermore, laser microdissection-reverse-transcriptase-polymerase chain reaction analysis confirmed the high Ifi202 expression in all areas of B6.MRLc1(82-100) kidneys. In conclusion, in the Ifi200 family, Ifi202 expressions in the kidney and immune organs significantly increased with GN progression.
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PMID:Overexpression of interferon-activated gene 202 (Ifi202) correlates with the progression of autoimmune glomerulonephritis associated with the MRL chromosome 1. 2016 32

Scleroderma renal crisis is characterized by malignant hypertension and oligo-anuric acute renal failure. Scleroderma renal crisis occurs in 2 to 5% of patients with systemic sclerosis, particularly those with diffuse cutaneous systemic sclerosis in the first years of disease evolution. High-dose corticosteroid therapy (> 15 mg/d) is associated with an increased risk of scleroderma renal crisis. Patients present with prominent left heart failure and hypertensive encephalopathy. Renal failure can be associated with moderate proteinuria, without hematuria. Thrombotic microangiopathy is detected in 43% of the cases. Anti-RNA polymerase III antibodies are present in one third of patients with scleroderma renal crisis. In case of renal failure, iatrogenic or functional origin must be investigated, as well as crescentic glomerulonephritis associated with antineutrophil cytoplasm antibodies (ANCA) or thrombotic microangiopathy. Renal biopsy is not necessary to establish the diagnosis in typical forms of scleroderma renal crisis. However, it can help to evaluate the prognosis and it is recommended when clinical presentation of scleroderma renal crisis is unusual. The prognosis of scleroderma renal crisis dramatically improved with the use of angiotensin-converting enzyme (ACE) inhibitors. However, 5-year survival of patients who developed a scleroderma renal crisis is only 65%. The treatment relies on the early control of blood pressure with increasing doses of ACE inhibitors, in association with calcium channel blockers if necessary. In case of severe renal failure and/or hypertension, dialysis can help to quickly control the vascular overload and the blood pressure. Dialysis can be stopped in about half of cases. After 2 years on dialysis, eligible patients should be considered for renal transplantation. The prevention of scleroderma renal crisis lacks consensus. Corticosteroids and/or nephrotoxic drugs should be avoided in patients with diffuse cutaneous systemic sclerosis.
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PMID:[Renal involvement in patients with systemic sclerosis]. 2152 52


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