Donathe Vetter

Max-Delbrück-Centrum für Molekulare Medizin, Berlín, Berlin, Germany

Are you Donathe Vetter?

Claim your profile

Publications (4)25.57 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In double transgenic rats (dTGR) harboring the human angiotensinogen (hAOGEN) and human renin (hREN) genes, we studied cardiac transcript levels of hypertrophy-related, Ca(2+) regulatory, and beta-adrenoceptor-associated proteins. The contractile properties and the cellular signaling of isolated hearts exposed to (-)isoproterenol and/or angiotensin (Ang) I were evaluated. dTGR developed hypertension of 174.1+/- 7.6 versus 109.6 +/- 2.0 mm Hg (P<0.05) in Sprague-Dawley rats and heart hypertrophy. In hearts of dTGR, the transcript levels of ANP, beta-MHC, and alpha-MHC were altered (percentage versus Sprague-Dawley rats, 100%) by 304%, 178%, and 78%, respectively. Transcript levels of L-type Ca(2+) channel, Ca(2+) release channel, SERCA2a, phospholamban, G(i)- and G(s)-proteins were unchanged. Isolated hearts of dTGR indicated higher baseline contractility versus Sprague-Dawley rats. (-)Isoproterenol-modified contractility occurred in both groups; however, the extent (predrug value, 100%) was less in hearts of dTGR versus Sprague-Dawley rats (+dP/dt, 310 +/- 42% versus 534 +/- 63%; P<0.05). Interestingly, (-)isoproterenol shortened the relaxation time by equivalent to 25% in both groups. This finding was reflected by a protein kinase A-related phospholamban phosphorylation. Ang I depressed the heart contractility but did not interact with the protein kinase A pathway. In conclusion, we have found that expression of the hAOGEN-hREN complex in dTGR elicited specific effects on transcripts of ANP and myofibrillar proteins. Although the beta-adrenergically mediated relaxation was not impaired in the hypertrophied hearts, the extent of beta-adrenergic inotropic responsiveness was reduced.
    Preview · Article · Feb 2002 · Hypertension
  • [Show abstract] [Hide abstract]
    ABSTRACT: The site-specific phospholamban phosphorylation was studied with respect to the interplay of cAMP- and Ca2+signaling in neonatal rat cardiomyocytes. To elucidate the signal pathway(s) for the activation of Ca2+/calmodulin-dependent protein kinase (CaMKII) we studied Thr17 phosphorylation of phospholamban in dependence of Ca2+channel activation by S(-)-Bay K8644 and in dependence of the depletion of the sarcoplasmic reticulum Ca2+stores by ryanodine or thapsigargin in the absence or presence of β -adrenergic stimulation. The isoproterenol (0.1 μM)-induced Thr17 phosphorylation was potentiated 2.5-fold in presence of 1 μM S(-)-Bay K8644. Interestingly, S(-)-Bay K8644 alone was also able to induce Thr17 phosphorylation in a dose- and time-dependent fashion. Ryanodine (1.0 μM) reduced both the isoproterenol (0.1μM ) and S(-)-Bay K8644-(1 μM) mediated Thr17 phosphorylation by about 90%. Thapsigargin (1 μM) diminished the S(-)-Bay K8644 and isoproterenol-associated Thr17 phosphorylation by 53.5±6.3% and 92.5±11.1%, respectively. Ser16 phosphorylation was not affected under these conditions. KN-93 reduced the Thr17 phosphorylation by S(-)-Bay K8644 and isoproterenol to levels of 1.1±0.3% and 8.6±2.1%, respectively. However, the effect of KN-93 was attenuated (47.8±3.6%) in isoproterenol prestimulated cells. Protein phosphatase inhibition by okadaic acid increased exclusively the Ser16 phosphorylation. In summary, our results reflect a cross-talk between β -adrenoceptor stimulation and intracellular Ca2+at the level of CaMKII-mediated phospholamban phosphorylation in neonatal rat cardiomyocytes. We report conditions which exclusively produce Thr17 or Ser16 phosphorylation. We postulate that Ca2+transport systems of the sarcoplasmic reticulum are critical determinants for the activation of CaMKII that catalyzes phosphorylation of phospholamban.
    No preview · Article · Dec 2000 · Journal of Molecular and Cellular Cardiology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Catecholamines hasten cardiac relaxation through beta-adrenergic receptors, presumably by phosphorylation of several proteins, but it is unknown which receptor subtypes are involved in human ventricle. We assessed the role of beta1- and beta2-adrenergic receptors in phosphorylating proteins implicated in ventricular relaxation. Right ventricular trabeculae, obtained from freshly explanted hearts of patients with dilated cardiomyopathy (n=5) or ischemic cardiomyopathy (n=5), were paced at 60 bpm. After measurement of the contractile and relaxant effects of epinephrine (10 micromol/L) or zinterol (10 micromol/L), mediated through beta2-adrenergic receptors, and of norepinephrine (10 micromol/L), mediated through beta1-adrenergic receptors, tissues were freeze clamped. We assessed phosphorylation of phospholamban, troponin I, and C-protein, as well as specific phosphorylation of phospholamban at serine 16 and threonine 17. Data did not differ between the 2 disease groups and were therefore pooled. Epinephrine, zinterol, and norepinephrine increased contractile force to approximately the same extent, hastened the onset of relaxation by 15+/-3%, 5+/-2%, and 20+/-3%, respectively, and reduced the time to half-relaxation by 26+/-3%, 21+/-3%, and 37+/-3%. These effects of epinephrine, zinterol, and norepinephrine were associated with phosphorylation (pmol phosphate/mg protein) of phospholamban 14+/-3, 12+/-4, and 12+/-3; troponin I 40+/-7, 33+/-7, and 31+/-6; and C-protein 7.2+/-1.9, 9.3+/-1.4, and 7.5+/-2.0. Phosphorylation of phospholamban occurred at both Ser16 and Thr17 residues through both beta1- and beta2-adrenergic receptors. Norepinephrine and epinephrine hasten human ventricular relaxation and promote phosphorylation of implicated proteins through both beta1- and beta2-adrenergic receptors, thereby potentially improving diastolic function.
    Preview · Article · Jan 1999 · Circulation
  • Source

    Preview · Article ·