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Your search keyword '"Tremmel, K. D."' showing total 5 results
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5 results on '"Tremmel, K. D."'

3. Cardiac adrenergic receptor effects of carvedilol

Author

Yoshikawa, T., primary, Port, J. D., additional, Asano, K., additional, Chidiak, P., additional, Bouvier, M., additional, Dutcher, D., additional, Roden, R. L., additional, Minobe, W., additional, Tremmel, K. D., additional, and Bristow, M. R., additional

Published
1996
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4. Regulation of the mRNA-binding protein AUF1 by activation of the beta-adrenergic receptor signal transduction pathway.

Author

Pende, A, Tremmel, K D, DeMaria, C T, Blaxall, B C, Minobe, W A, Sherman, J A, Bisognano, J D, Bristow, M R, Brewer, G, and Port, J

Abstract

In both cell culture based model systems and in the failing human heart, beta-adrenergic receptors ( beta-AR) undergo agonist-mediated down-regulation. This decrease correlates closely with down-regulation of its mRNA, an effect regulated in part by changes in mRNA stability. Regulation of mRNA stability has been associated with mRNA-binding proteins that recognize A + U-rich elements within the 3'-untranslated regions of many mRNAs encoding proto-oncogene and cytokine mRNAs. We demonstrate here that the mRNA-binding protein, AUF1, is present in both human heart and in hamster DDT1-MF2 smooth muscle cells and that its abundance is regulated by beta-AR agonist stimulation. In human heart, AUF1 mRNA and protein was significantly increased in individuals with myocardial failure, a condition associated with increases in the beta-adrenergic receptor agonist norepinephrine. In the same hearts, there was a significant decrease (approximately 50%) in the abundance of beta1-AR mRNA and protein. In DDT1-MF2 cells, where agonist-mediated destabilization of beta2-AR mRNA was first described, exposure to beta-AR agonist resulted in a significant increase in AUF1 mRNA and protein (approximately 100%). Conversely, agonist exposure significantly decreased (approximately 40%) beta2-adrenergic receptor mRNA abundance. Last, we demonstrate that AUF1 can be immunoprecipitated from polysome-derived proteins following UV cross-linking to the 3'-untranslated region of the human beta1-AR mRNA and that purified, recombinant p37AUF1 protein also binds to beta1-AR 3'-untranslated region mRNA.

Published
1996

5. Selective downregulation of the angiotensin II AT1-receptor subtype in failing human ventricular myocardium.

Author

Asano K, Dutcher DL, Port JD, Minobe WA, Tremmel KD, Roden RL, Bohlmeyer TJ, Bush EW, Jenkin MJ, Abraham WT, Raynolds MV, Zisman LS, Perryman MB, and Bristow MR

Subjects
Adult, Angiotensin II analogs & derivatives, Angiotensin II metabolism, Cell Membrane metabolism, Down-Regulation, Female, Heart Failure pathology, Heart Ventricles, Humans, Kinetics, Male, Myocardium pathology, Polymerase Chain Reaction, Radioligand Assay, Receptor, Angiotensin, Type 1, Receptor, Angiotensin, Type 2, Receptors, Adrenergic, beta-1 metabolism, Receptors, Adrenergic, beta-2 metabolism, Reference Values, Cardiomyopathy, Dilated metabolism, Heart Failure metabolism, Myocardium metabolism, Receptors, Angiotensin biosynthesis
Abstract

Background: The regulation of angiotensin II receptors and the two major subtypes (AT1 and AT2) in chronically failing human ventricular myocardium has not been previously examined., Methods and Results: Angiotensin II receptors were measured by saturation binding of 125I-[Sar1,Ile8]angiotensin II in crude membranes from nonfailing (n = 19) and failing human left ventricles with idiopathic dilated cardiomyopathy (IDC; n = 31) or ischemic cardiomyopathy (ISC; n = 21) and membranes from a limited number of right ventricles in each category. The AT1 and AT2 fractions were determined by use of an AT1-selective antagonist, losartan. beta-Adrenergic receptors were also measured by binding of 125I-iodocyanopindolol with the beta 1 and beta 2 fractions determined by use of a beta 1-selective antagonist, CGP20712A, AT1 but not AT2 density was significantly decreased in the combined (IDC + ISC) failing left ventricles (nonfailing: AT1 4.66 +/- 0.48, AT2 2.73 +/- 0.39; failing: AT1 3.20 +/- 0.29, AT2 2.70 +/- 0.33 fmol/mg protein; mean +/- SE). The decrease in AT1 density was greater in the IDC than in the ISC left ventricles (IDC: 2.73 +/- 0.40, P < .01; ISC: 3.89 +/- 0.39 fmol/mg protein, P = NS versus nonfailing). beta 1 but not beta 2 density was decreased in the failing left ventricles. AT1 density was correlated with beta 1 density in all left ventricles (r = .43). AT1 density was also decreased in IDC right ventricles. In situ reverse transcription-polymerase chain reaction in sections of nonfailing and failing ventricles indicated that AT1 mRNA was present in both myocytes and nonmyocytes., Conclusions: AT1 receptors are selectively downregulated in failing human ventricles, similar to the selective downregulation of beta 1 receptors. The relative lack of AT1 downregulation in ISC hearts may be related to differences in the degree of ventricular dysfunction.

Published
1997
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