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)

Acid-sensing ion channels (ASICs) are a new and expanding family of proton-gated cation (Na+/Ca2+) channels that are widely expressed in sensory neurons and the central nervous system. Their distribution suggests that they may play a critical role in the sensation of the pain that accompanies tissue acidosis and may also be important in detecting the subtle pH variations that occur during neuronal signalling. Here, using whole-cell patch-clamp electrophysiology and reverse transcriptase-polymerase chain reaction (RT-PCR), we show that HEK293 cells, a commonly used cell line for the expression and characterisation of many ion channels, functionally express an endogenous proton-gated conductance attributable to the activity of human ASIC1a. These data therefore represent the first functional characterisation of hASIC1 and have many important implications for the use of HEK293 cells as a host cell system for the study of ASICs, vanilloid receptor-1 and any other proton-gated channel. With this latter point in mind we have devised a simple desensitisation strategy to selectively remove the contribution of hASIC1a from proton-gated currents recorded from HEK293 cells expressing vanilloid receptor-1.
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PMID:Characterisation of a human acid-sensing ion channel (hASIC1a) endogenously expressed in HEK293 cells. 1151 22

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

Cortical spreading depression (CSD) may be the underlying mechanism of migraine aura. The role of CSD in initiating a migraine headache remains to be determined, but it might involve specific changes in gene expression in the brain. To examine these changes, four episodes of CSD at 5-minute intervals were induced in the mouse brain by application of 300mM KCl, and gene expression was examined 2 hours later using cDNA array and reverse transcriptase-polymerase chain reaction. Controls consisted of groups that received anesthesia only, attachment of recording electrodes only, and application of 0.9% NaCl. Of the over 1,180 genes examined in our experiments, those consistently regulated by CSD included vasoactive peptides; the vasodilator atrial natriuretic peptide was induced by CSD, while the vasoconstrictor neuropeptide Y was downregulated. Other genes specifically regulated by CSD were involved in oxidative stress responses (major prion protein, glutathione-S-transferase-5, and apolipoprotein E). L-type calcium channel mRNA was upregulated. In summary, CSD regulates genes that are intrinsic to its propagation, that identify accompanying vascular responses as a potential source of pain, and that protect against its potential pathological consequences. We believe these observations have strong relevance to the mechanisms of migraine and its outcomes.
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PMID:Cortical spreading depression and gene regulation: relevance to migraine. 1192 Oct 56

Opioid receptors (OR) are involved in many physiological and pathological immune functions. During recent years, the treatment of opiate addiction with methadone in HIV-positive and HIV-negative patients has become widely accepted. However, little is known on the occurrence and course of OR on lymphocytes of these individuals. The objective of the study was to detect and quantify OR on peripheral white blood cells (WBC) by fluorescence-activated cell sorting using polyclonal antibodies and reverse transcriptase polymerase chain reaction, and to assess the influence of HIV infection and methadone treatment. We compared OR levels in 80 HIV-positive homosexuals, 18 HIV-positive intravenous drug users (IVDU) treated with methadone, 18 HIV-negative IVDU receiving methadone and 25 healthy controls. HIV infection was shown to decrease the amount of OR on WBC, especially of the delta-subtype on lymphocytes and granulocytes. The decrease correlated with the duration of HIV-infection (P<0.01), and inversely with the HIV viral load (P<0.01). In contrast, chronic methadone administration led to a significant increase of OR exclusively in HIV-negative IVDU. In particular the delta-OR was increased by 31-, 62- and 42-fold on lymphocytes, monocytes and granulocytes of HIV-negative patients (each P<0.005), respectively, which was not observed in HIV-positive IVDU. Therefore, HIV seems to reduce OR particularly on lymphocytes and granulocytes regardless of the mode of HIV transmission. The quantification of OR on immune cells may help to elucidate the effects of opioid analogues in health and drug addiction.
Pain 2002 Jul
PMID:Opioid receptors on white blood cells: effect of HIV infection and methadone treatment. 1209 31

The presence of a neuropeptide AF and FF receptor (NPFF-R2) mRNA in human adipose tissue (Elshourbagy, N. A., Ames, R. S., Fitzgerald, L. R., Foley, J. J., Chambers, J. K., Szekeres, P. G., Evans, N. A., Schmidt, D. B., Buckley, P. T., Dytko, G. M., Murdock, P. R., Tan, K. B., Shabon, U., Nuthulaganti, P., Wang, D. Y., Wilson, S., Bergsma, D. J., and Sarau, H. M. (2000) J. Biol. Chem. 275, 25965-25971) suggested these peptides, principally recognized for their pain modulating effects, may also impact on adipocyte metabolism, an aspect that has not been explored previously. Our aim was thus to obtain more insights into the actions of these peptides on adipocytes, an approach initially undertaken with a functional genomic assay. First we showed that 3T3-L1 adipocytes express both NPFF-R1 and NPFF-R2 transcripts, and that NPAF binds adipocyte membranes with a nanomolar affinity as assessed by surface plasmon resonance technology. Then, and following a 24-h treatment with NPFF or NPAF (1 microm), we have measured using real-time quantitative reverse transcriptase-PCR the mRNA steady state levels of already well characterized genes involved in key pathways of adipose metabolism. Among the 45 genes tested, few were modulated by NPFF ( approximately 10%) and a larger number by NPAF ( approximately 27%). Interestingly, NPAF increased the mRNA levels of beta2- and beta3-adrenergic receptors (AR), and to a lesser extent those of beta1-ARs. These variations in catecholamine receptor mRNAs correlated with a clear induction in the density of beta2- and beta3-AR proteins, and in the potency of beta-AR subtype-selective agonists to stimulate adenylyl cyclase activity. Altogether, these data show that NPFF-R1 and NPFF-R2 are functionally present in adipocytes and suggest that besides their well described pain modulation effects, NPAF and to a lesser extent NPFF, may have a global impact on body energy storage and utilization.
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PMID:Neuropeptide AF and FF modulation of adipocyte metabolism. Primary insights from functional genomics and effects on beta-adrenergic responsiveness. 1214 60

Synovitis of the subacromial bursa has been identified as a main source of shoulder pain in rotator cuff diseases. Little interest, however, has been paid into the synovitis of glenohumeral joint. The mRNA expression levels of interleukin-1beta (IL-1beta) and interleukin-1 receptor antagonists produced in the synovitis reflect the magnitude of inflammation. The present study was undertaken to determine the relationship between mRNA expression levels of IL-1beta and its receptor antagonists (secreted interleukin-1 receptor antagonist (IL-1ra) and intracellular IL-1ra) in the synovium of the glenohumeral joint and shoulder pain in rotator cuff diseases, analyzing the synovial specimens by reverse transcriptase polymerase chain reaction. Thirty-five patients with rotator cuff diseases were candidates. Based on the presence of cuff perforation, they were divided into two categories: 16 with non-perforating tears and 19 with perforating tears. The degree of shoulder pain was evaluated by use of a visual analogue scale. The pain degree of non-perforating tears was significantly greater than that of perforating tears (P < 0.01). In contrast, the expression levels of the cytokine-mRNAs were constitutively greater in perforating tears than in non-perforating tears (P < 0.01, respectively). The expression levels of the cytokine-mRNAs were inversely correlated with the degree of pain (IL-1beta: r = 0.930; secreted IL-1ra: r = 0.861; intracellular IL-1ra: r = 0.932, P < 0.001 respectively). These results suggest that the expression levels of the cytokine-mRNAs in the synovium of the glenohumeral joint contribute less to the generation of shoulder pain in rotator cuff diseases.
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PMID:Interleukin-1-induced glenohumeral synovitis and shoulder pain in rotator cuff diseases. 1247 54

Spinal nerve ligation results in dramatic changes in spinal cord primary C-afferent fibers, which include atrophy with an accompanied decrease in calcitonin-gene-related peptide (CGRP). These changes parallel the activation of astrocytes, which have been implicated in the ensuing neuropathic pain states. As part of an effort to elucidate the role of the downstream effectors of astrocyte reactivity in the context of allodynia, the expression of fibroblast growth factor-2 (FGF-2) was examined following tight ligation of L5 and L6 spinal nerves. FGF-2 is a pleiotropic cytokine that is synthesized and secreted by neurons and astrocytes. FGF-2 immunoreactivity was increased in ipsilateral dorsal horn reactive astrocytes at 1 and 3 weeks following nerve ligation. Semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) of laser-captured dorsal spinal cord sections revealed an increase in FGF-2 mRNA in the dorsal horn ipsilateral to nerve injury compared to contralateral and SHAM. Furthermore, an increase in FGF-2 mRNA in ispilateral dorsal root ganglia (DRG) was seen by in situ hybridization. These results demonstrate that, in response to ligation-induced injury of sensory neurons, FGF-2 is upregulated in both DRG neurons and in spinal cord astrocytes, suggesting neurotrophic functions of this growth factor following peripheral nerve lesion and possibly in astrocyte-related maintenance of pain states.
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PMID:Upregulation of FGF-2 in reactive spinal cord astrocytes following unilateral lumbar spinal nerve ligation. 1254 Nov 47

An adhesion of the subacromial bursa in the shoulder causes pain during joint motion and restricts the range of motion of the glenohumeral joint. To understand the biologic features of an adhesion, the gene expressions in adhesive subacromial bursa were analyzed by quantitative real-time reverse transcriptase-polymerase chain reaction. The gene expressions in adhesive subacromial bursae were approximately threefold to fourfold greater than those in nonadhesive bursae for the genes for Type I and Type III procollagens, CD34 antigen in vascular endothelium, hyaluronan synthase-3, and interferon-gamma. The gene expression of interleukin-8 was predominant in adhesive bursa. The gene expressions of hyaluronan synthase-1, hyaluronan synthase-2, and interleukin-10 which is an antiadhesive cytokine were predominant in nonadhesive bursae. Chromatography analysis revealed that a hyaluronan, of which molecular weight was more than 100 kDa, was present in the cavity of nonadhesive subacromial bursae. It is suggested that pathologic fibrosis and vascularization are maintained by the presence of interferon-gamma and interleukin-8 in adhesive subacromial bursae and that high molecular weight hyaluronan or interleukin-10 plays a role for antiadhesion.
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PMID:Pathologic gene expression in adhesive subacromial bursae of human shoulder. 1283 53

A 55-year-old bat conservationist was admitted to Ninewells Hospital, Dundee, Scotland, on November 11, 2002, with an acute haematemesis. He gave a 5-day history of pain and paraesthesia in the left arm, followed by increasing weakness of his limbs with evidence of an evolving encephalitis with cerebellar involvement. The patient had never been vaccinated against rabies and did not receive postexposure treatment. Using a hemi-nested reverse transcriptase-polymerase chain reaction (RT-PCR), saliva samples taken intravitam from different dates proved positive for rabies. A 400-bp region of the nucleoprotein gene was sequenced for confirmation and identified a strain of European bat lyssavirus (EBLV) type 2a. The diagnosis was confirmed using the fluorescent antibody test (FAT) and by RT-PCR on three brain samples (cerebellum, medulla, and hippocampus) taken at autopsy. In addition, a mouse inoculation test (MIT) was performed. Between 13 and 17 days postinfection, clinical signs of a rabies-like illness had developed in all five inoculated mice. Brain smears from each infected animal were positive by the FAT and viable virus was isolated. This fatal incident is only the second confirmed case of an EBLV type-2 infection in a human after exposure to bats.
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PMID:Case report: isolation of a European bat lyssavirus type 2a from a fatal human case of rabies encephalitis. 1293 4

Fibromyalgia and chronic hepatitis C infection share many clinical features including prominent somatic complaints such as musculoskeletal pain and fatigue. There is a growing body of evidence supporting a link between cytokines and somatic complaints. This review discusses alterations of cytokines in fibromyalgia, including increased serum levels of interleukin (IL)-2, IL-2 receptor, IL-8, IL-1 receptor antagonist; increased IL-1 and IL-6 produced by stimulated peripheral blood mononuclear cell in patients with FM for longer than 2 years; increased gp130, which is a neutrophil cytokine transducing protein; increased soluble IL-6 receptor and soluble IL-1 receptor antagonist only in patients with fibromyalgia who are depressed; and IL-1 beta, IL-6, and TNF-a by reverse transcriptase-polymerase chain reaction in skin biopsies of some patients with fibromyalgia. In addition, this review describes the mechanism by which alterations in cytokines in fibromyalgia and chronic hepatitis C infection can produce hyperalgesia and other neurally mediated symptoms through the presence of cytokine receptors on glial cells and opiate receptors on lymphocytes and the influence of cytokines on the hypothalamus-pituitary-adrenal axis such as IL-1, IL-6, and TNF-a activating and IL-2 and IFN-a down-regulating the HPA axis, respectively. The association between chronic hepatitis C infection and fibromyalgia is discussed, including a description of key cytokine changes in chronic hepatitis C infection. Future studies are encouraged to further characterize these immunologic alterations with potential pathophysiologic and therapeutic implications.
Curr Pain Headache Rep 2003 Oct
PMID:Fibromyalgia, hepatitis C infection, and the cytokine connection. 1294 86


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