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Kenneth R Chien - One of the best experts on this subject based on the ideXlab platform.

  • hras dependent pathways can activate morphological and genetic markers of cardiac muscle cell hypertrophy
    Journal of Biological Chemistry, 1993
    Co-Authors: Andrew Thorburn, Jacqueline Thorburn, Seiyu Chen, Scott Powers, H E Shubeita, James R Feramisco, Kenneth R Chien
    Abstract:

    We have investigated the role of the proto-oncogene HRas in cardiac cell growth and hypertrophy. By direct needle microinjection of activated Ras protein into primary neonatal rat ventricular cardiac myocytes, we find that, unlike many other cell types, Ras does not induce DNA synthesis in these cells. However, injection of activated Ras does induce expression of both the c-Fos and atrial natriuretic factor (ANF) genes. Expression of both these genes is associated with the hypertrophic response in ventricular myocytes suggesting that Ras is involved in the hypertrophic signalling pathway. Ras injection also causes morphological changes in the cells so that they increase in profile and show changes in the organization of the contractile apparatus. Further support for a role for Ras in the hypertrophic response was obtained from studies showing that activated Ras stimulates ANF promoter activity in transient transfection assays. We also show that a dominant interfering Ras mutant inhibits the hypertrophic stimulation of the ANF promoter by phenylephrine, indicating a role for Ras in the hypertrophic effect of an Alpha-Adrenergic Agonist.

  • transcriptional activation of the cardiac myosin light chain 2 and atrial natriuretic factor genes by protein kinase c in neonatal rat ventricular myocytes
    Proceedings of the National Academy of Sciences of the United States of America, 1992
    Co-Authors: H E Shubeita, Kenneth R Chien, E A Martinson, M Van Bilsen, Joan Heller Brown
    Abstract:

    Abstract A cultured myocardial cell model was used to examine the role of protein kinase C-dependent pathways in the transcriptional activation of two cardiac muscle genes [myosin light chain 2 (MLC-2) and atrial natriuretic factor (ANF)] during Alpha-Adrenergic receptor-mediated hypertrophy. Phorbol ester (phorbol 12-myristate 13-acetate) and the Alpha-Adrenergic Agonist phenylephrine both activate protein kinase C (PKC) and induce 4- to 5-fold increases in the expression of MLC-2 and ANF promoter/luciferase reporter genes with little effect on Rous sarcoma virus/luciferase or minimal prolactin promoter/luciferase genes. To further assess the role of PKC in cardiac gene regulation, PKC expression vectors encoding constitutively activated PKC-alpha or PKC-beta, or a catalytically inactive PKC, were transiently cotransfected with the cardiac promoter/luciferase constructs. Cotransfection of either activated PKC-alpha or PKC-beta cDNA induces the expression of MLC-2 and ANF promoter/luciferase genes and of a reporter gene responsive to the transcription factor AP-1. The Rous sarcoma virus/luciferase and minimal prolactin promoter/luciferase genes are not concomitantly induced by cotransfectin with the PKC genes, indicating specificity of the transcriptional effect. The finding that activated PKC increases cardiac gene transcription suggests that activation of this enzyme may be a proximal signal for coregulation of two cardiac genes, MLC-2 and ANF, during the course of myocardial cell hypertrophy.

H E Shubeita - One of the best experts on this subject based on the ideXlab platform.

  • hras dependent pathways can activate morphological and genetic markers of cardiac muscle cell hypertrophy
    Journal of Biological Chemistry, 1993
    Co-Authors: Andrew Thorburn, Jacqueline Thorburn, Seiyu Chen, Scott Powers, H E Shubeita, James R Feramisco, Kenneth R Chien
    Abstract:

    We have investigated the role of the proto-oncogene HRas in cardiac cell growth and hypertrophy. By direct needle microinjection of activated Ras protein into primary neonatal rat ventricular cardiac myocytes, we find that, unlike many other cell types, Ras does not induce DNA synthesis in these cells. However, injection of activated Ras does induce expression of both the c-Fos and atrial natriuretic factor (ANF) genes. Expression of both these genes is associated with the hypertrophic response in ventricular myocytes suggesting that Ras is involved in the hypertrophic signalling pathway. Ras injection also causes morphological changes in the cells so that they increase in profile and show changes in the organization of the contractile apparatus. Further support for a role for Ras in the hypertrophic response was obtained from studies showing that activated Ras stimulates ANF promoter activity in transient transfection assays. We also show that a dominant interfering Ras mutant inhibits the hypertrophic stimulation of the ANF promoter by phenylephrine, indicating a role for Ras in the hypertrophic effect of an Alpha-Adrenergic Agonist.

  • transcriptional activation of the cardiac myosin light chain 2 and atrial natriuretic factor genes by protein kinase c in neonatal rat ventricular myocytes
    Proceedings of the National Academy of Sciences of the United States of America, 1992
    Co-Authors: H E Shubeita, Kenneth R Chien, E A Martinson, M Van Bilsen, Joan Heller Brown
    Abstract:

    Abstract A cultured myocardial cell model was used to examine the role of protein kinase C-dependent pathways in the transcriptional activation of two cardiac muscle genes [myosin light chain 2 (MLC-2) and atrial natriuretic factor (ANF)] during Alpha-Adrenergic receptor-mediated hypertrophy. Phorbol ester (phorbol 12-myristate 13-acetate) and the Alpha-Adrenergic Agonist phenylephrine both activate protein kinase C (PKC) and induce 4- to 5-fold increases in the expression of MLC-2 and ANF promoter/luciferase reporter genes with little effect on Rous sarcoma virus/luciferase or minimal prolactin promoter/luciferase genes. To further assess the role of PKC in cardiac gene regulation, PKC expression vectors encoding constitutively activated PKC-alpha or PKC-beta, or a catalytically inactive PKC, were transiently cotransfected with the cardiac promoter/luciferase constructs. Cotransfection of either activated PKC-alpha or PKC-beta cDNA induces the expression of MLC-2 and ANF promoter/luciferase genes and of a reporter gene responsive to the transcription factor AP-1. The Rous sarcoma virus/luciferase and minimal prolactin promoter/luciferase genes are not concomitantly induced by cotransfectin with the PKC genes, indicating specificity of the transcriptional effect. The finding that activated PKC increases cardiac gene transcription suggests that activation of this enzyme may be a proximal signal for coregulation of two cardiac genes, MLC-2 and ANF, during the course of myocardial cell hypertrophy.

H Kammermeier - One of the best experts on this subject based on the ideXlab platform.

  • signals mediating stimulation of cardiomyocyte glucose transport by the alpha adrenergic Agonist phenylephrine
    American Journal of Physiology-cell Physiology, 1996
    Co-Authors: Yvan Fischer, J Kamp, Julia Thomas, S Popping, H Rose, C Carpene, H Kammermeier
    Abstract:

    Phenylephrine, a potent stimulator of cardiomyocyte glucose transport (GT), caused a rapid rise in cytosolic Ca2+ by 30%. Agents inducing a similar Ca2+ response did not stimulate (angiotension II, vasopressin) or inhibited GT by 20% (elevated extracellular Ca2+). Stimulation of GT by phorbol myristate acetate was additive to both phases of phenylephrine's effect (4 min, 60 min). Phenylephrine had no influence on the adenosine 3', 5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) levels. Agents raising cAMP (isoproterenol) or cGMP (e.g., nitroprusside) did not stimulate GT. Wortmannin (inhibitor of 1-phosphatidylinositol 3-kinase) suppressed the action of insulin on GT but not that of phenylephrine. In contrast, the Na+/H+ exchange inhibitor amiloride (which blocks phenylephrine-induced cytosolic alkalinization or even lowers cellular pH) depressed the effect of phenylephrine by 50%, whereas insulin-stimulated GT was little affected. However, raising extracellular pH up to 8.4 failed to increase GT. Lowering pH to 6.8 decreased phenylephrine's effect by 40% whereas insulin-dependent GT was not significantly altered. Clorgyline, tranylcypromine (monoamine oxidase inhibitors), and added catalase suppressed the slow phase of phenylephrine's action, whereas amiloride also affected the fast phase. We conclude that 1) stimulation of cardiomyocyte GT by phenylephrine does not involve cAMP, cGMP, or 1-phosphatidylinositol 3-kinase; 2) protein kinase C activation cannot explain the full extent of stimulation; 3) Ca2+ release or cytosolic alkalinization may be required but is not sufficient to trigger phenylephrine's action, and 4) the slow phase of stimulation is mediated by the monoamine oxidase-dependent degradation of phenylephrine and by the resulting H2O2 formation.

Joan Heller Brown - One of the best experts on this subject based on the ideXlab platform.

  • transcriptional activation of the cardiac myosin light chain 2 and atrial natriuretic factor genes by protein kinase c in neonatal rat ventricular myocytes
    Proceedings of the National Academy of Sciences of the United States of America, 1992
    Co-Authors: H E Shubeita, Kenneth R Chien, E A Martinson, M Van Bilsen, Joan Heller Brown
    Abstract:

    Abstract A cultured myocardial cell model was used to examine the role of protein kinase C-dependent pathways in the transcriptional activation of two cardiac muscle genes [myosin light chain 2 (MLC-2) and atrial natriuretic factor (ANF)] during Alpha-Adrenergic receptor-mediated hypertrophy. Phorbol ester (phorbol 12-myristate 13-acetate) and the Alpha-Adrenergic Agonist phenylephrine both activate protein kinase C (PKC) and induce 4- to 5-fold increases in the expression of MLC-2 and ANF promoter/luciferase reporter genes with little effect on Rous sarcoma virus/luciferase or minimal prolactin promoter/luciferase genes. To further assess the role of PKC in cardiac gene regulation, PKC expression vectors encoding constitutively activated PKC-alpha or PKC-beta, or a catalytically inactive PKC, were transiently cotransfected with the cardiac promoter/luciferase constructs. Cotransfection of either activated PKC-alpha or PKC-beta cDNA induces the expression of MLC-2 and ANF promoter/luciferase genes and of a reporter gene responsive to the transcription factor AP-1. The Rous sarcoma virus/luciferase and minimal prolactin promoter/luciferase genes are not concomitantly induced by cotransfectin with the PKC genes, indicating specificity of the transcriptional effect. The finding that activated PKC increases cardiac gene transcription suggests that activation of this enzyme may be a proximal signal for coregulation of two cardiac genes, MLC-2 and ANF, during the course of myocardial cell hypertrophy.

Dulavová Martina - One of the best experts on this subject based on the ideXlab platform.

  • Nová HPLC metoda pro stanovení nafazolinu v očních přípravcích
    Univerzita Karlova Farmaceutická fakulta v Hradci Králové, 2011
    Co-Authors: Dulavová Martina
    Abstract:

    Univerzita Karlova v Praze, Farmaceutická fakulta v Hradci Králové Katedra analytické Chemie Kandidát: Martina Dulavová Školitel: PharmDr. Lucie Havlíková, Ph.D.; Ass.Prof. Hannelore Kopelent Název diplomové práce: Nová HPLC metoda pro stanovení naphazolinu v očních přípravcích Naphazolin je derivátem 2-imidazolinu a také alfa-adrenergní Agonista s vasokonstrikčními a dekongescenčními vlastnostmi. Naphazolin je používán při terapii rinitidy, sinusitidy nebo alergické konjunktivitidy. Pro oční a nosní podání je používán ve formě vodných přípravků. Naphazolin je prodáván ve velkém množství komerčně dostupných produktů, jako je například Coldan® Augentropfen (oční kapky). V nemocničních lékárnách se z ekonomických a tereapeutických důvodů dává přednost individuálně připravovaným přípravkům s naphazolinem. V naší práci byly analyzovány dva odlišné preparáty obsahující naphazolin připravené ve sterilních podmínkách v nemocniční lékárně. První přípravek je složen ze dvou komerčně dostupných přípravků, je to směs Coldan® Augentropfen a Okuzell® Augentropfen v poměru 1:9. Druhý přípravek je Bor-Naphazolin Augentropfen, který je kompletně připravován v nemocniční lékárně. Tyto přípravky obsahují kromě naphazolinu pomocné látky benzalkonium chlorid a kyselinu boritou. Cílem práce bylo testovat výše uvedené...Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Analytical Chemistry Candidate: Martina Dulavová Supervisor: PharmDr. Lucie Havlíková, Ph.D., Ass.Prof. Hannelore Kopelent Title of Diploma Thesis: A New Selective and Stability Indicating HPLC Assay for the Determination of Naphazoline in Preparations for Ocular Use Naphazoline is a 2-imidazolidine derivated drug and Alpha-Adrenergic Agonist with vasoconstrictive and decongestive properties. Naphazoline is indicated for the therapy of rhinitis, sinusitis or allergic conjunctivitis. Naphazoline is used in liquid formulations for ophthalmic and nasal application. Naphazoline is marketed in a number of commercially available products; for example, it is contained in Coldan® Augentropfen. Due to economic and therapeutic reasons, hospital pharmacies produce miscellaneous in-house preparations. For our study, two different preparations manufactured in the sterile production of a hospital pharmacy containing naphazoline are investigated. The first formulation is based on two commercially available products and it is a mixture of Coldan® Augentropfen and Okuzell® Augentropfen at a ratio of 1:9. The second formulation is Bor-Naphazolin Augentropfen and it is completely prepared in a hospital pharmacy. In addition to...Department of Analytical ChemistryKatedra analytické chemieFaculty of Pharmacy in Hradec KrálovéFarmaceutická fakulta v Hradci Králov

  • Nová HPLC metoda pro stanovení nafazolinu v očních přípravcích
    2011
    Co-Authors: Dulavová Martina
    Abstract:

    Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Analytical Chemistry Candidate: Martina Dulavová Supervisor: PharmDr. Lucie Havlíková, Ph.D., Ass.Prof. Hannelore Kopelent Title of Diploma Thesis: A New Selective and Stability Indicating HPLC Assay for the Determination of Naphazoline in Preparations for Ocular Use Naphazoline is a 2-imidazolidine derivated drug and Alpha-Adrenergic Agonist with vasoconstrictive and decongestive properties. Naphazoline is indicated for the therapy of rhinitis, sinusitis or allergic conjunctivitis. Naphazoline is used in liquid formulations for ophthalmic and nasal application. Naphazoline is marketed in a number of commercially available products; for example, it is contained in Coldan® Augentropfen. Due to economic and therapeutic reasons, hospital pharmacies produce miscellaneous in-house preparations. For our study, two different preparations manufactured in the sterile production of a hospital pharmacy containing naphazoline are investigated. The first formulation is based on two commercially available products and it is a mixture of Coldan® Augentropfen and Okuzell® Augentropfen at a ratio of 1:9. The second formulation is Bor-Naphazolin Augentropfen and it is completely prepared in a hospital pharmacy. In addition to..