Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type V and VI adenylyl cyclase mRNAs are the two main cyclase isoforms expressed in the mammalian heart. A recent report has shown that their expression is differentially regulated during ontogenic development, but the accumulation of the two mRNA species and their concentration ratio have not been determined. We thus determined the accumulation and the relative amounts of type V and VI adenylyl cyclase mRNA in fetal, neonatal and adult rat hearts, using a sensitive ribonuclease protection assay. In 18-day-old fetuses, the two adenylyl cyclase mRNA isoforms were weakly expressed in approximately equal amounts (type V mRNA/type VI mRNA = 0.93 +/- 0.09). Further development was characterized by a sharp increase in type V adenylyl cyclase mRNA (x 1.9 in neonates v fetuses, P < 0.01; x 2.4 and x 4.5 in adults v neonates and fetuses, respectively, P < 0.01 for both comparisons) and a slight, non-significant fall in type VI mRNA (P = 0.16). As a result, the type V mRNA/type VI mRNA ratio was 2.86 +/- 0.57 and 9.09 +/- 1.21 in neonatal hearts and adult ventricles, respectively (P < 0.01 v ratio in fetal hearts for both comparisons; P < 0.01 for ratio in adult ventricles v ratio in neonatal hearts), and the overall amount of the two mRNA isoforms was 2.3 times greater in adult than in fetal hearts (P < 0.01). This increase was paralleled by an increase in basal and isoproterenol- and forskolin-stimulated adenylyl cyclase activities in adult hearts compared to fetal and neonatal hearts (P < 0.01 for the three comparisons). Our results demonstrate that type V adenylyl cyclase mRNA accumulates in the rat heart after birth to become the highly predominant isoform in the adult heart. They further suggest that the increase in cardiac adenylyl cyclase activity observed during rat development is due to this accumulation.
J Mol Cell Cardiol 1995 Sep
PMID:Type V, but not type VI, adenylyl cyclase mRNA accumulates in the rat heart during ontogenic development. Correlation with increased global adenylyl cyclase activity. 852 40

Adriamycin is a potent, broad-spectrum chemotherapeutic agent effective against solid tumors and malignant hematological disease. The major limiting factor for adriamycin is its cardiotoxicity. Thus, the objective of this study was to investigate the role of cardiomyocyte and endothelial cell apoptosis in adriamycin-induced cardiomyopathy, in vivo and in vitro. For in vivo study, intraperitoneal injections of adriamycin were administered to nine adult male Wistar rats and normal saline to six rats as control. Eight of the nine rats in the adriamycin group, but none in the control group, developed marked ascites and DNA ladders in agarose gel electrophoresis of genomic DNA extracted from the rat hearts (P<0.001). The ratio of apoptotic nuclei in the cardiomyocytes was significantly higher for the adriamycin-treated rats (162+/-149/10(6) cells) than for the controls (4.2+/-1.3/10(6) cells; P<0.01) by TUNEL assay. Increased endothelial cell apoptosis was detected in the small coronary vessels of the myocardium of the adriamycin-treated rats. Increased immuno-reactive Caspase-3 expression was also noted for both cardiomyocytes and endothelial cells of adriamycin-treated rats. In vitro adriamycin treatment for cultured neonatal rat cardiomyocytes and human umbilical vein endothelial cells, respectively, showed a dose-related increase in apoptosis as determined by flowcytometry, DNA ladder analysis, TUNEL assay and/or electron-microscope examination. A dose-related increase in the expression of Fas antigen, Bax and Caspase-3, as well as a decrease in the expression of Bcl-2, were determined for the adriamycin-treated cardiomyocytes using Northern blot analysis, reverse transcriptase polymerase chain reaction (RT-PCR) and ribonuclease protection assay. RT-PCR also revealed increased Fas antigen expression, decreased Bcl-2 expression, and no change in Bax expression for the adriamycin-treated human umbilical vein cells. Further, pretreatment with broad caspase inhibitor, but not neutralizing FasL antibody, resulted in inhibition of adriamycin-induced endothelial cell apoptosis. In conclusion, these results indicate that both adriamycin-induced cardiomyocyte and endothelial cell death can occur via apoptosis which is dose-related, and can occur both in vitro and in vivo with changes in the expression of the apoptosis-related genes. Adriamycin-induced endothelial cell apoptosis is mediated by caspase activation but is Fas/FasL signal pathway independent. Our data provides evidence that both cardiomyocyte and endothelial cell apoptosis may play an important role in adriamycin-induced cardiomyopathy.
J Mol Cell Cardiol 2002 Dec
PMID:Adriamycin-induced cardiomyocyte and endothelial cell apoptosis: in vitro and in vivo studies. 1250 58

In congestive heart failure (CHF), cardiac sympathetic nerve endings transdifferentiate from a balanced norepinephrine (NE) storage/release/uptake apparatus to a nerve that predominantly releases NE. Little is known about the neurotrophic factors that may trigger this process. In the present study, we evaluated the cardiac expression pattern of nerve growth factor (NGF), neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) in salt-sensitive Dahl rats (DS), which are characterized by profound alterations of the cardiac sympathetic nervous system. Experiments were performed in male DS and salt-resistant Dahl rats (DR) 30, 40 and 50 days after onset of high-salt intake. The sympathetic nerve density was measured by glyoxylic acid-induced histofluorescence. Cardiac NE re-uptake was assessed by isolated heart perfusion with [(3)H]-NE and norepinephrine transporter (NET) mRNA by real-time PCR. Cardiac expression of neurotrophic factors was determined by ribonuclease protection assay and Western blot analysis. DS rats displayed reduced left ventricular sympathetic nerve endings 40 days after onset of high-salt intake, which was preceded by an impaired cardiac [(3)H]-NE uptake. NGF, a positive regulator of NE re-uptake, and NT-3 were down-regulated already 30 days after onset of high-salt intake, whereas BDNF and CNTF protein expression were increased not before 40 days after onset of high-salt intake. In conclusion, during the development of CHF, a dysregulated NE storage/release/uptake apparatus within the sympathetic nerve endings might be triggered by differential expression of cardiac neurotrophic factors.
J Mol Cell Cardiol 2008 Feb
PMID:Differential expression of cardiac neurotrophic factors and sympathetic nerve ending abnormalities within the failing heart. 1803 33