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 myocardial ischemia and reperfusion injury is caused by the re-introduction of coronary circulation in ischemic myocardial tissues. A number of experiments demonstrate that immunological response such as adherence of neutrophils to endothelial cells play a critical role in reperfusion injury. In this paper, the effect of global ischemia and reperfusion on the expression of cytokine genes by myocardial tissues as well as cell adhesion molecules by neutrophils were studied by using Langendorff model. Cardiac dysfunction and immunological response in 25 min global ischemia at 37.5 degrees C followed by 60 min reperfusion were studied in isolated rat heart perfused with blood supplied from support rat (Langendorff model). Cardiac functions were measured with a left intraventricular balloon. The mean post-experimental reduction of the left ventricular end-systolic pressure were 87.5 +/- 1.6% of pre-experimental level in the control perfusion group and 55.5 +/- 5.8% in the reperfusion group. Immunofluorescence flow cytometry showed that ischemia and reperfusion injury did not affect the expression of adhesion molecules on neutrophils which were isolated from perfused blood samples. Cytokine gene expression was analyzed by direct analysis of mRNA obtained from the blood-perfused, isolated rat heart. The level of expression of the cytokine genes was assessed using semiquantitative reverse transcriptase-polymerase chain reaction (semiquantitative RT-PCR). IL-6, IL-8, IFN-gamma, TNF-alpha were expressed in normal heart tissue at low level and were upregulated following ischemia and reperfusion. IL-1 beta, MCP-1 and IL-1 receptor antagonist were not expressed at detectable level in normal heart but were induced following global ischemia. IL-1 alpha was not expressed at detectable level in normal heart but was induced following reperfusion of the ischemic heart. Histological examination of myocardial tissue from the reperfusion group revealed no evidence of myocardial necrosis. Only a mild interstitial edema as well as weak focal hemorrhage was detected after reperfusion of ischemic hearts. These results suggest that there is a process which causes early stage of post-ischemic myocardial dysfunction without involving myocardial necrosis nor infiltration of inflammatory cells.
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PMID:[Cardiac dysfunction and endogenous cytokines in global ischemia and reperfusion injury]. 811 7

1. We have examined the expression of endothelin isoforms and their precursors in the human heart using RIA, HPLC, immunocytochemistry and reverse transcriptase-polymerase chain reaction assays. 2. Highly specific RIAs were used to measure the levels of mature endothelin and big endothelin-1 immunoreactivity in extracts of human right ventricle. There was no significant difference between samples from patients with ischaemic heart disease and idiopathic dilated cardiomyopathy. 3. HPLC coupled with RIAs allowed the separation and identification of the three mature isoforms of endothelin, big endothelin-1 and the C-terminal fragment of big endothelin-1. In extracts of human endocardial endothelial cells, peaks of immunoreactivity that co-eluted with authentic endothelin-1, big endothelin-1 and C-terminal fragment were found. 4. Intense immunocytochemical staining of mature endothelin immunoreactivity was detected in the cytoplasm of endothelial cells of all regions of the heart tested. Big endothelin-1 immunoreactivity mirrored that of the mature peptide and, in two of three individuals tested, big endothelin-2 immunoreactivity was also detected. No big endothelin-3 immunoreactivity was detected in any of the tissues examined. 5. Reverse transcriptase-polymerase chain reaction assays demonstrated endothelin-1 and endothelin-2 mRNA in all three samples of human left ventricle tested. In two of the individuals, additional bands were also detected with the endothelin-2 primers which corresponded to splice variants. There was no evidence for the expression of endothelin-3 mRNA. 6. These data suggest that endothelin-1 is the predominant isoform of endothelin in the human heart and is probably largely synthesized by the endothelial cells within the heart. If released from the endothelial cells in vivo, this potent cardiotonic peptide may play an important paracrine role in human cardiovascular function.
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PMID:Expression of endothelin peptides and mRNA in the human heart. 869 4

An activation of protein kinase C (PKC) in acute myocardial ischemia has been shown previously using its translocation to the plasma membrane as an indirect parameter. However, whether PKC remains activated or whether other mechanisms such as altered gene expression may mediate an isozyme-specific regulation in prolonged ischemia have not been investigated. In isolated perfused rat hearts, PKC activity and the expression of PKC cardiac isozymes were determined on the protein level using enzyme activities and Western blot analyses and on the mRNA level using reverse transcriptase-polymerase chain reaction after various periods of global ischemia (1 to 60 minutes). As early as 1 minute after the onset of ischemia, PKC activity is translocated from the cytosol to the particulate fraction without change in total cardiac enzyme activity. This translocation involves all major cardiac isozymes of PKC (ie, PKCalpha, PKCdelta, PKCepsilon, and PKCzeta). This rapid, nonselective activation of PKCs is only transient. In contrast, prolonged ischemia (>/=15 minutes) leads to an increased cardiac PKC activity (119+/-7 versus 190+/-8 pmol/min per mg protein) residing in the cytosol. This is associated with an augmented, subtype-selective isozyme expression of PKCdelta and PKCvarepsilon (163% and 199%, respectively). The specific mRNAs for PKCdelta (948+/-83 versus 1501+/-138 ag/ng total RNA, 30 minutes of ischemia) and PKCepsilon (1597+/-166 versus 2611+/-252 ag/ng total RNA) are selectively increased. PKCalpha and PKCzeta remain unaltered. In conclusion, two distinct activation and regulation processes of PKC are characterized in acute myocardial ischemia. The early, but transient, translocation involves all constitutively expressed cardiac isozymes of PKC, whereas in prolonged ischemia an increased total PKC activity is associated with an isozyme-selective induction of PKCepsilon and PKCdelta. Whether these fundamentally different activation processes interact remains to be elucidated.
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PMID:Two distinct mechanisms mediate a differential regulation of protein kinase C isozymes in acute and prolonged myocardial ischemia. 1040 Sep 13

1. Soybean phytoestrogens have no oestrogen agonist effects on the reproductive system and therefore it is reasonable to explore the potential of these naturally occurring plant oestrogens in the cardiovascular pathology. We therefore investigated the effects of genistein in a rat model of myocardial ischaemia-reperfusion injury. 2. Anaesthetized rats were subjected to total occlusion (45 min) of the left main coronary artery followed by 5 h reperfusion (MI/R). Sham operated rats were used as controls. Myocardial necrosis, myocardial myeloperoxidase activity (MPO), serum creatinine phosphokinase activity (CPK), serum and macrophage Tumour Necrosis Factor-alpha (TNF-alpha), cardiac intercellular adhesion molecule-1 (ICAM-1) immunostaining, cardiac mRNA for ICAM-1 evaluated by the means of reverse transcriptase polymerase chain reaction (RT - PCR), ventricular arrhythmias and myocardial contractility (left ventricle dP/dt(max)) were evaluated. 3. Myocardial ischaemia and reperfusion in untreated rats produced marked myocardial necrosis, increased serum CPK activity and MPO activity both in the area-at-risk and in the necrotic area, reduced myocardial contractility, caused ventricular arrhythmias and induced a marked increase in serum and macrophage TNF-alpha. Furthermore myocardial ischaemia-reperfusion injury increased ICAM-1 expression in the myocardium. 4. Administration of genistein (1 mg kg(-1), i.v., 5 min after coronary artery occlusion) lowered myocardial necrosis and MPO activity in the area-at-risk and in the necrotic area, decreased serum CPK activity, increased myocardial contractility, decreased the occurrence of ventricular arrhythmias, reduced serum and macrophages levels of TNF-alpha and blunted ICAM-1 expression in the injured myocardium. Finally genistein added in vitro to peritoneal macrophages collected from untreated rats subjected to myocardial ischaemia-reperfusion injury significantly reduced TNF-alpha production. 5. Our data suggest that genistein limits the inflammatory response and protects against myocardial ischaemia-reperfusion injury.
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PMID:Cardioprotection by the phytoestrogen genistein in experimental myocardial ischaemia-reperfusion injury. 1058 23

HIV-specific protease inhibitors(PI) have been available in Japan since 1997. Since then, highly active anti-retroviral therapy(HAART) including two reverse transcriptase inhibitors combined with PI became the main strategy of HIV treatment. After introducing HAART, incidence of most opportunistic infections dramatically decreased, resulted a steep decline of AIDS death in Japan as well as in the United States. However, several unexpected problems related to HAART have been coming up. One is a lipodystrophy syndrome(LDS) which is a novel side effect caused by PI. Lipid disposition was noted associated with hyperlipidemia and/or hyperglycemia. Ischemic heart diseases will emerge in patients with LDS in future. Another one is inflammatory reactions to some opportunistic pathogens, such as Mycobacteria, Pneumocystis carinii, cryptococcus, and so on, occurred during course of immune reconstitution after HAART. This reaction is sometimes too severe to continue HAART and corticosteroid is often required to control the reaction. How to diagnose and how to manage the reaction are to be determined in future.
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PMID:[Current HIV therapy and its clinical problems]. 1105 80

In the human fetus IGFBP-3 mRNA expression is most abundant in the skin, muscle and heart but circulating IGFBP-3 levels show age-related variations. In human heart tissues from controls and patients with either ischemic, dilated or hypertrophic cardiomyopathy (no.: 20, age-range from fetuses to elderly subjects) we determined the expression of cardiac IGFBP-3 mRNA by reverse transcriptase polymerase chain reaction (RT-PCR) and the protein by Western blotting. The same parameters were also determined in human livers. We detected IGFBP-3 mRNA in neonatal and adult as well as in fetal human heart tissues in both ventricles. Western blotting revealed the presence of IGFBP-3 in all the examined cardiac tissues. IGFBP-3 appeared to be more abundant in the heart than in the liver and in the failing hearts from patients with ischemic heart disease than in those with hypertrophic cardiomyopathy. Thus both normal and pathological human heart tissues express IGFBP-3 across lifespan and IGFBP-3 could play IGF-dependent and/or -independent actions at the myocardial level.
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PMID:Neonatal and adult human heart tissues from normal subjects and patients with ischemic, dilated or hypertrophic cardiomyopathy express insulin-like growth factor binding protein-3 (IGFBP-3). 1119 4

The insulin-like growth factors (IGFs), IGF-I and IGF-II, play important roles in normal growth and differentiation. In recent studies, IGFs have been implicated in tissue repair and regeneration after hypoxicischemic injury. The growth effects of these genes are exerted primarily through IGF-I receptor (IGF-IR). We have earlier shown that picroliv, obtained from the roots of Picrorhiza kurrooa, reduces cellular damage caused by hypoxia in vitro. We have now studied the modulation of IGF-I, IGF-II and IGF-IR in hypoxia and the ability of picroliv to modify their expression in vivo. Male Sprague-Dawley rats, placed in 10% oxygen for 4 days, were sacrificed, and the expression of IGF-I, IGF-II and IGF-IR was determined by immunohistochemistry, in situ hybridization and reverse transcriptase polymerase chain reaction (RT-PCR) in brain, liver and lung. One group of animals was pretreated with picroliv and the other served as control. IGF-I and IGF-IR were expressed in distinct regions of the brain but not in liver or lung. IGF-I was mainly expressed in the hippocampus and cerebellum, whereas IGF-IR expression was also observed in the cortex. A significant reduction in the messenger RNA (mRNA) level of these genes was observed in response to hypoxia. Pretreatment with picroliv not only prevented such downregulation but more importantly resulted in increased levels of IGF-I and IGF-IR. These observations correlated with reduced neuronal cell death observed in these animals. The mRNA of IGF-II was constitutively expressed and was not altered by hypoxia. Modulation of IGF-I and IGF-II expression by picroliv, a novel pharmacological agent, could benefit in similar clinical settings such as myocardial ischemia and certain cerebral injuries.
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PMID:Picroliv modulates the expression of insulin-like growth factor (IGF)-I, IGF-II and IGF-I receptor during hypoxia in rats. 1121 61

Platelets play an important role in the coronary thrombus formation that leads to myocardial ischemia and infarction. Gender differences in the development of coronary heart disease and its outcomes are partly regulated by estrogen and its receptors, but the roles of the latter in thrombogenicity are less well-defined. We previously demonstrated the presence of estrogen receptor (ER) beta in cells of the megakaryocytic lineage. In this study, we characterize human platelet ERbeta and its expression using biochemical and molecular biological techniques. Western immunoblotting showed that platelet ERbeta migrated with an apparent molecular mass approximately 3.7 kDa larger than ERbeta in a variety of cell lines (including those of prostate and breast origin). A rigorous investigation of platelet ERbeta mRNA by reverse transcriptase-polymerase chain reaction revealed normal transcripts and a single alternately spliced mRNA. However, this variant form was smaller, lacking exon 2, and could not account for the larger protein size seen in platelets. Treatment of ERbeta with N-glycosidase F, which removes core carbohydrate residues, caused a more rapid migration through polyacrylamide gels but had no effect on ERbeta from human cell lines. We conclude that the larger form of ERbeta in human platelets is not attributable to alternate mRNA splicing but primarily to tissue-specific glycosylation.
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PMID:Human platelets contain a glycosylated estrogen receptor beta. 1123 Jan 12

Vascular endothelial growth factor (VEGF) is an angiogenic mitogen, specific for endothelial cells. Hypoxia-induced VEGF in endothelial cells and cardiomyocytes leads to autocrine and paracrine stimulation, respectively. During myocardial ischemia, VEGF is upregulated in the endothelium and myocardium, and may mediate angiogenesis. Morphine sulfate is commonly used in pain relief for patients with acute myocardial infarction. We investigated the effect of morphine sulfate on VEGF expression in cultured endothelial cells and cardiac myocytes subjected to hypoxia. Enzyme-linked immunosorbent assays showed that morphine sulfate significantly inhibited hypoxia-induced VEGF expression in mouse heart microvascular endothelial cells (SMHEC4), primary cultures of human umbilical vein endothelial cells (HUVECs) and in primary cultures of rat cardiac myocytes (P<0.05). Real time reverse transcriptase polymerase chain reaction showed that morphine treatment (100 ng/ml) of hypoxic HUVECs resulted in a significant reduction in mRNA levels of VEGF(121) and VEGF(165) isoforms. Transfection of HUVECs with a human VEGF promoter-luciferase construct showed that hypoxia-induced transcriptional activation of VEGF was markedly inhibited by morphine sulfate (P<0.05). Phosphatidyl inositol-3 kinase and protein kinase C-mediated activation of the VEGF promoter was also inhibited by morphine. The opioid antagonist naloxone significantly reversed the inhibitory effects of morphine in endothelial cells suggesting the involvement of opioid receptors. Our results show that the inhibitory effects of morphine on hypoxia-induced VEGF expression in endothelial cells and cardiac myocytes can lead to a decrease in the autocrine and paracrine stimulation and hence limit neovascularization of the ischemic myocardium.
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PMID:Morphine sulfate inhibits hypoxia-induced vascular endothelial growth factor expression in endothelial cells and cardiac myocytes. 1173 63

The phenotypic and functional changes of coronary arteries with aging promote ischemic heart disease. We hypothesized that these alterations reflect an aging-induced proinflammatory shift in vascular regulatory mechanisms. Thus, in isolated coronary arteries of young (3-month-old) and aged (25-month-old) male Fischer 344 rats the expression of 96 cytokines, chemokines, and their receptors were screened by a cDNA-based microarray technique. In aged vessels expressions of tumor necrosis factor (TNF)-alpha (3.3x), interleukin (IL)-1beta (3.0x), IL-6 (2.9x), IL-6Ralpha (2.8x) and IL-17 (6.1x) genes were significantly increased over young vessels. Quantitative reverse transcriptase-polymerase chain reaction confirmed these results. Western blotting demonstrated that protein expressions of TNF-alpha, IL-1beta, IL-6, and IL-17 were also significantly increased in vessels of aged rats compared with those of young rats. Immunofluorescent double labeling showed that in aged vessels IL-1beta and IL-6 are predominantly localized in the endothelium, whereas TNF-alpha and IL-17 are localized in smooth muscle. Thus, a proinflammatory shift in the profile of vascular cytokine expression may contribute to the aging-induced phenotypic changes in coronary arteries, promoting the development of ischemic heart disease in the elderly.
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PMID:Aging-induced proinflammatory shift in cytokine expression profile in coronary arteries. 1270 2


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