Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allopurinol, Collins' solution, and spermidine were tested for their ability to preserve nuclear function during kidney storage. Spermidine increased nuclear ribonucleic acid (RNA) polymerase activity 25 to 43 percent after 60 minutes of warm ischemia. Collins' solution was less effective and allopurinol did not protect RNA polymerase activity. Spermidine offered little additional protection over Collins' during cold storage of RNA polymerase activity. Only spermidine prevented the decrease in the molecular weight of RNA transcribed following kidney storage. Only Collins' solution prevented the breakdown of rapidly labeled heterogenous high molecular weight RNA and ribosomal precursor RNA.
 ...
PMID:Protection of nuclear function by various agents during organ storage. 84 69

The responses of long and short half-lived proteins to ischemia were measured in rat brain during 6 days of recovery from 30 min of transient forebrain ischemia produced by four-vessel occlusion. At the end of the ischemic interval, the neocortical activities of four vulnerable enzymes [ornithine (ODC) and S-adenosylmethionine (SAMDC) decarboxylases, and RNA polymerases I and II] were unchanged, but within 30 min of reperfusion, their activities dropped by 25-50%. The loss of substance P in the striatum and substantia nigra was slower, reaching about 50% by 12 h. On the other hand, the activities of 5 long half-lived enzymes did not change in the neocortex at 5 and 15 h of reperfusion and regional protein concentrations were essentially unaffected over 6 days survival. The rate and extent of normalization of the amounts or activities of the vulnerable proteins varied. RNA polymerase II and ODC activities were restored within 4 h, and ODC showed a biphasic increase in activity, with peaks at 10 h and 2-3 days. RNA polymerase I and SAMDC activities were restored by 18 h and 5 days, respectively, whereas substance P concentrations did not completely recover, even at 6-15 days. The greater the regional reduction of blood flow during ischemia, the larger the net change (gain or loss) of SAMDC or ODC activity and the longer the time required to normalize the activities of these enzymes. The average rate of proteolysis, assessed by measuring the rate of clearance of 14C from protein prelabeled with [14C]bicarbonate, was abnormal during the first 2 days of reperfusion. Postischemic changes in both protein synthesis and degradation could affect the amounts of some of the proteins responsive to transient ischemia.
 ...
PMID:Temporal profiles of proteins responsive to transient ischemia. 257 82

The low-molecular peptide fractions are obtained from the brain of experimental and control animals by the method which includes sedimentation of high-molecular compounds and gel-filtration on Sephadex G-10. Ischemia of the rat brain sharply changes the amino acidic composition of the isolated peptide fractions. An inhibitory effect of the studied fractions on the activity of DNA-dependent RNA polymerase as well as their effect on the heat denaturation of exogenous DNA are established.
 ...
PMID:[Isolation and characteristics of peptide fractions from the rat brain in ischemia]. 407 80

Ischemia, anoxia, and hypoxia of the brain have been shown to inhibit protein synthesis in the central nervous system. To obtain data on the changes in DNA-dependent RNA and DNA polymerase as they pertain specifically to neurons and glia, nuclear enriched neuronal and glial fractions were prepared, by sucrose-gradient centrifugation, from spinal cords of adult dogs that had been subjected to prolonged ischemia. The isolated fractions were assayed for enzyme activity by a radiochemical technique. RNA polymerase was affected more than DNA polymerase, activity being reduced considerably in both neurons and glia. Possible causes of the difference in sensitivity to ischemia are discussed.
 ...
PMID:Effect of ischemia on the activity of DNA-dependent RNA polymerase and DNA polymerase. 725 10

Protein tyrosine phosphorylation is thought to play an important role in the regulation of neural function. To elucidate the role that protein tyrosine phosphatases (PTPs) may play in the postischemic brain, PTPs expressed in regions of the rat brain vulnerable to transient forebrain ischemia were examined. With the reverse-transcriptase polymerase chain reaction using degenerate primers, three PTPs, STEP, PTP delta, and SH-PTP2, were identified. They were expressed in the hippocampus 12 h after transient ischemia for 20 min. During the reperfusion period, the mRNA levels of these PTPs were not different from those in sham-operated rats. In contrast, a fourfold increase in the mRNA level of CL100 (3CH134), a PTP that is inducible by oxidative stress, was detected by Northern blotting in the hippocampus and cerebral cortex 1 h after the onset of reperfusion. In situ hybridization histochemistry showed a slight increase in the level of CL100 mRNA in neuronal cells in the hippocampus and cortex of postischemic rats compared to control rats. These findings suggest that PTPs play a role in the normal function of the hippocampus and cerebral cortex and demonstrate that ischemia induced CL100 expression.
 ...
PMID:Induction of CL100 protein tyrosine phosphatase following transient forebrain ischemia in the rat brain. 779 38

Ischemia/reperfusion injury associated with organ retrieval and storage influences the development of chronic graft dysfunction, the major clinical problem in solid organ transplantation. The potential role of mononuclear cells (T cells and monocyte/macrophages) in this type of injury is unknown. Inbred male Lewis rats were uninephrectomized and the left kidney perfused in situ with 10 ml of iced University of Wisconsin solution. Immunohistological studies showed mononuclear cell infiltration of the ischemic organs associated with the upregulation of MHC class II antigen expression. Reverse transcriptase-PCR indicated that T cell associated cytokines and monocyte/macrophage activation markers/products are upregulated early after the ischemic insult. B7 expression occurred within 24 h and peaked at 3 d. Plasma creatinine levels rose transiently with complete recovery of renal function by 5 d. Animals began to develop progressive proteinuria after 8-12 wk, indicative of the long-term functional consequences of early ischemia/reperfusion injury. Blockade of T cell CD28-B7 costimulation with CTLA4Ig resulted in significant inhibition of T cell and macrophage infiltration and activation in situ. Treated animals did not exhibit transient renal dysfunction, nor developed proteinuria over time. This is the first demonstration that blocking T cell costimulatory activation in the absence of alloantigen can prevent the early and late consequences of ischemia/reperfusion injury.
 ...
PMID:The role of the B7 costimulatory pathway in experimental cold ischemia/reperfusion injury. 927 37

Interleukin-1 (IL-1) is a proinflammatory cytokine produced by blood-borne and resident inflammatory lung tissue involved in the thrombotic occlusion of the pulmonary microcirculation and the increase of the vascular permeability following a wide variety of injuries and sepsis. The locally accentuated, organ-related activation of this cytokine seems to be responsible for the development of acute lung injury. The present study was conducted to determine if IL-1beta was produced in an ischemia-reperfusion (I/R) rat model subjected to lung injury. We measured sequential perfusate levels of IL-1beta by ELISA and we measured IL-1 gene expression in the rat lung tissue by a reverse-transcriptase polymerase chain reaction method. Little IL-1beta gene expression was observed in normal rat lung tissue. Perfusate IL-1beta slightly increased 2 h after induced ischemia and 3 h after reperfusion. IL-1beta gene expression rapidly increased as early as 30 min after ischemia and continued to increase for up to 120 min. IL-1beta gene expression was dramatically upregulated during reperfusion after cessation of ischemia, reached a peak at 1 h, and then gradually decreased (2 to 3 h) to near baseline levels. During ischemia, the increased IL-1 gene expression was not significantly different between the ventral and dorsal sites of the lung. However, IL-1 gene expression markedly increased on the dorsal part (the dependent site for a rat in a supine position) after reperfusion. From these results, it appears that IL-1 may have an important role in I/R lung injury.
 ...
PMID:Interleukin-1 in ischemia-reperfusion acute lung injury. 935 26

Activation of the complement system has been implicated in the pathogenesis of myocardial ischemia/reperfusion injury. It has always been assumed that liver is the primary source of complement components. In the present study, we used the reverse-transcriptase polymerase chain reaction technique to establish that the mRNAs for complement proteins C3 and C9 are expressed in rabbit heart. Rabbit liver, brain, spleen, and kidney were also shown to express C3 and C9 mRNAs. We used Western blotting to establish that these mRNAs in heart are translated into the corresponding proteins. We further established that dramatic upregulation of the mRNAs occurred in Langendorff-perfused isolated hearts subjected to ischemia and reperfusion. C3 mRNA was always expressed at higher levels than was C9 mRNA, but C9 mRNA showed greater upregulation under stress. Compared with levels in control hearts subjected to 5 minutes of normoxic perfusion, hearts subjected to 0.5 hours of ischemia followed by 1 hour of reperfusion had a 4.72-fold increase in C3 mRNA and a 19.5-fold increase in C9 mRNA. By contrast, C3 mRNA in hearts subjected to 3.5 hours of normoxic perfusion showed no change, and those subjected to 3.5 hours of ischemia showed only a 1.72-fold increase, whereas C9 mRNA levels increased by 5.17-fold after 3.5 hours of normoxic perfusion and 12.5-fold after 3.5 hours of ischemia. The results of this study demonstrate for the first time that heart tissue is capable of expressing genes and proteins of the complement system, although it is not yet known which cell types are responsible. They further demonstrate that ischemia and reperfusion of the heart promotes a rapid upregulation of the mRNAs encoding the complement proteins C3 and C9 and that these abnormal levels considerably exceed those of normal liver. These observations are consistent with the hypothesis that local production of complement proteins may contribute significantly to the degree of ischemic injury to the myocardium and that complement expression is augmented by reperfusion.
 ...
PMID:Complement gene expression by rabbit heart: upregulation by ischemia and reperfusion. 963 21

Transcription factors are nuclear proteins with an ability to recognize particular nucleotide sequences on double stranded genomic DNAs and thereby modulate the activity of RNA polymerase II which is responsible for the formation of messenger RNAs in cell nuclei. Gel retardation electrophoresis revealed that transient forebrain ischemia for 5 min led to drastic potentiation of binding of a radiolabelled double-stranded oligonucleotide probe for the transcription factor activator protein-1, in the thalamus as well as the CA1 and CA3 subfields and the dentate gyrus of the hippocampus of the gerbils previously given ischemia for 2 min two days before, which is known to induce tolerance to subsequent severe ischemia in the CA1 subfield. By contrast, ischemia for 5 min resulted in prolonged potentiation of activator protein-1 binding in the vulnerable CA1 subfield of the gerbils with prior ischemia for 5 min 14 days before, which is shown to induce delayed death of the pyramidal neurons exclusively in this subfield. Similar prolongation was seen with activator protein-1 binding in the vulnerable thalamus but not in the resistant CA3 subfield and dentate gyrus of the gerbils with such repeated ischemia for 5 min. Limited proteolysis by Staphylococcus aureus V8 protease as well as supershift assays using antibodies against c-Fos and c-Jun proteins demonstrated the possible difference in constructive partner proteins of activator protein-1 among nuclear extracts of the CA1 subfield obtained from gerbils with single, tolerated and repeated ischemia. These results suggest that de novo protein synthesis may underlie molecular mechanisms associated with acquisition of the ischemic tolerance through modulation at the level of gene transcription by activator protein-1 composed of different constructive partner proteins in the CA1 subfield. Possible participation of glial cells in the modulation is also suggested in particular situations.
 ...
PMID:Possible involvement of activator protein-1 DNA binding in mechanisms underlying ischemic tolerance in the CA1 subfield of gerbil hippocampus. 969 45

Interleukin-1 (IL-1) and tumor necrosis factor (TNF) are cytokines commonly associated with inflammatory conditions such as hepatic injury after ischemia-reperfusion. FR167653 has been characterized as a potent suppressant of IL-1beta and TNF-alpha production. In this study, we evaluated the effect of FR167653 in an extended liver resection with ischemia in a dog model. The right portal pedicle was clamped for 60 minutes, while the left portal branch was patent to avoid portal congestion. Following reperfusion, 75% of the liver (including the right central, quadrate, left central, left lateral, and papillary lobes) were resected. Animals were divided into two groups: a control group (n = 10), and a FR-treated group (n = 6) in which FR167653 was administered via the portal vein. Hepatic venous blood was collected to measure alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), purine nucleoside phosphorylase (PNP), and hyaluronic acid (HA) levels, and IL-1beta expression was also measured by reverse-transcriptase polymerase chain reaction (RT-PCR). ALT, AST, LDH, PNP, and HA levels after reperfusion were significantly lower (P < .05) in the FR-treated group than in the control group, and the FR-treated group showed inhibited IL-1beta expression. Liver tissue blood flow, measured by a laser Doppler flow meter, was kept higher in the FR-treated group than in the control group. Histologically, tissue damage was mild in the FR-treated group. The 2-day survival rate was statistically better (P < .05) in the FR-treated group than in the control group. We conclude that FR167653 provides a protective effect for liver parenchyma and sinusoidal endothelial cells in extended liver resection with ischemia.
 ...
PMID:The effects of FR167653 in extended liver resection with ischemia in dogs. 969 12


1 2 3 4 5 Next >>