Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A recent report has shown that in vitro the RAMP2/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells. However, in vivo, it is well known that CGRP receptors are expressed in human coronary arteries and that a beneficial effect is observed in patients after CGRP infusion of patients with congestive cardiac failure. This contrast may be explained by the in vivo impregnation of major hormones, so we have tested if glucocorticoids were able in vitro to enhance the expression of the RAMP1/CRLR expression leading to functional CGRP receptors. The expression of RAMP1, RAMP2, CRLR, and adrenomedullin was evaluated by semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR) using (33)P in human coronary arteries vascular smooth muscle cells (VSMC) cultured in the presence of dexamethasone. Under basal conditions, the CRLR mRNA was expressed, but RAMP2 mRNA was clearly more abundant than RAMP1 mRNA. Increases in CRLR and RAMP1 mRNA expressions occurred 4 h after treatment of VSMC with 10(-7) M dexamethasone and no change was found for RAMP2 mRNA. Adrenomedullin mRNA increased later, i.e., 8 and 16 h after dexamethasone treatment. The RAMP1 mRNA expression was elevated with doses of dexamethasone ranging from 10(-10) to 10(-7) M, thus a 5-fold increase in the ratio between RAMP1 and RAMP2 was observed with the lowest dose of dexamethasone and a 2-fold rise at 10(-7) M. CRLR mRNA levels were half-reduced with the two lowest doses of dexamethasone (10(-10) and 10(-9) M), but increased from 10(-8) to 10(-7) M. Thus, we suggest that, in vivo, glucocorticoids are involved in the expression of CGRP receptors by human coronary VSMC.
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PMID:Dexamethasone increases RAMP1 and CRLR mRNA expressions in human vascular smooth muscle cells. 1077 50

In order to characterize the expression of adrenomedullin during pregnancy, we measured the mature and total concentrations in maternal plasma and amniotic fluid, and examined its expression in fetoplacental tissues. Plasma samples were obtained from 13 normal normotensive non-pregnant women and 14 normal normotensive post partum women. Maternal plasma and amniotic fluid samples were obtained from 37 normal pregnant women (10 in the first trimester, 13 in the second trimester and 14 in the third trimester). Fetoplacental tissues were obtained from first and third-trimester pregnancies. Mature and total adrenomedullin concentrations in plasma and amniotic fluid were determined by using specific radioimmunoassay. The distribution and expression of adrenomedullin were determined using immunohistochemistry, reverse-transcriptase polymerase chain reaction, and in situ hybridization. Plasma total adrenomedullin concentrations were increasing with advancing gestation. The mature/total adrenomedullin ratio in the second trimester was the highest during pregnancy. Mature and total adrenomedullin concentrations in the amniotic fluid were significantly higher than those in the maternal plasma throughout gestation (P< 0.05). Mature adrenomedullin concentrations and the mature/total adrenomedullin ratio in the amniotic fluid increased with advancing gestation. There was a significant linear correlation between amniotic fluid and maternal plasma mature/total adrenomedullin ratio in the first or second trimester of pregnancy. Adrenomedullin mRNA was identified in the amniotic membrane and chorionic villi, and within the endothelial layers of villous blood vessels. These results suggest that the mature/total adrenomedullin ratio is modified in maternal plasma and amniotic fluid with advancing gestation.
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PMID:Change of adrenomedullin concentrations in plasma and amniotic fluid, and human placental adrenomedullin expression with advancing gestation. 1117 Aug 30

Adrenomedullin 2/intermedin (AM2/IMD) is a novel member of the calcitonin/calcitonin gene-related peptide (CGRP) peptide family. AM2/IMD has a vasodilator action, and antidiuretic and antinatriuretic effects in mice. The aim of the present study is to clarify immunolocalization of AM2/IMD in human hypothalamus, heart and kidney obtained at autopsy. Immunocytochemistry showed AM2/IMD-immunoreactive cell bodies in the paraventricular and supraoptic nuclei of human hypothalamus. Both parvocellular and magnocellular cells in the paravetricular nucleus are immunostained with AM2/IMD. Immunostaining of serial sections showed co-localization of AM2/IMD-like immunoreactivity and vasopressin in the paraventricular nucleus. Myocardial cells of the heart and renal tubular cells were positively immunostained with AM2/IMD, whereas neither renal glomeruli nor vasculature in the heart and kidney were immunostained. Reverse-transcriptase polymerase chain reaction confirmed expression of AM2/IMD mRNA in the brain, pituitary, heart and kidney. The present study has shown the wide expression of AM2/IMD in human hypothalamus, heart and kidney, raising the possibility that this novel peptide may be related to the central and peripheral regulation of the circulation and water-electrolyte metabolism.
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PMID:Immunocytochemical localization of adrenomedullin 2/intermedin-like immunoreactivity in human hypothalamus, heart and kidney. 1635 54

Adrenomedullin (AM) is a multifunctional regulatory peptide with important angiogenic and mitogenic properties. Here we identify a region of stable secondary structure in the 5'-untranslated region (5' UTR) of human AM mRNA. Reverse transcriptase-polymerase chain reaction of the 5' UTR consistently resulted, in addition to the product with the expected size of 155 base pair (bp), in a second product with an approximately 65-bp deletion from the central region of the 5' UTR, suggesting the presence of a secondary structure. The presence of a stem-loop structure was confirmed by probing the 5' UTR with RNases with selectivity for single- or double-stranded RNA. We investigated the role of this stem-loop structure in expression of luciferase reporter gene in cultured cell lines. Reporter assays using a chimeric mRNA that combined luciferase and the 5' UTR of AM mRNA demonstrated a dramatic decrease of the reporter activity owing to a decreased translation, whereas the deletion of the stem-loop structure localized between nt +31 and +95 from the cap site led to the recovery of activity. Gel migration shift assays using cytosolic extracts from mammalian cell lines demonstrate a specific binding of a cytosolic protein to riboprobes containing the 5' UTR of AM but not to riboprobes either corresponding to other areas of the message or containing the 5' UTR but lacking the region of secondary structure. Although we conclude that the 5' UTR of the human AM mRNA can modulate the translation of AM mRNA in vivo, and that the predicted stem-loop structure is necessary for this inhibition, the functional consequences of the cis element-binding activity remain to be determined.
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PMID:Identification of secondary structure in the 5'-untranslated region of the human adrenomedullin mRNA with implications for the regulation of mRNA translation. 1671 38