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Schott P Singer SS Kögler H Neddermeier D Leineweber K Brodde OE Regitz-Zagrosek V Schmidt B Dihazi H Hasenfuss G 《Proteomics》2005,5(5):1372-1381
Treatment with monocrotaline causes pulmonary hypertension in rats. This results in severe pressure overload-induced hypertrophy of the right ventricles, whilst the normally loaded left ventricles do not hypertrophy. Both ventricles are affected by enhanced neuroendocrine stimulation in this model. We analyzed in this model load-induced and catecholamine-induced changes of right and left ventricular proteome by two-dimensional gel electrophoresis, tryptic in-gel digest, and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. All analyzed animals showed right ventricular hypertrophy without signs of heart failure. Changes of 27 proteins in the right and 21 proteins in the left ventricular myocardium were found. Given the hemodynamic features of this animal model, proteome changes restricted to the right ventricle are caused by pressure overload. We describe for the first time a potentially novel pathway (BRAP2/BRCA1) that is involved in myocardial hypertrophy. Furthermore, we demonstrate that increased afterload-induced hypertrophy leads to striking changes in the energy metabolism with down-regulation of pyruvate dehydrogenase (subunit beta E1), isocitrate dehydrogenase, succinyl coenzyme A ligase, NADH dehydrogenase, ubiquinol-cytochrome C reductase, and propionyl coenzyme A carboxylase. These changes go in parallel with alterations of the thin filament proteome (troponin T, tropomyosin), probably associated with Ca(2+) sensitization of the myofilaments. In contrast, neurohumoral stimulation of the left ventricle increases the abundance of proteins relevant for energy metabolism. This study represents the first in-depth analysis of global proteome alterations in a controlled animal model of pressure overload-induced myocardial hypertrophy. 相似文献
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Lehnart SE Janssen PM Franz WM Donahue JK Lawrence JH Marbán E Prestle J Hasenfuss G 《American journal of physiology. Heart and circulatory physiology》2000,279(3):H986-H991
Adenoviral gene transfer to the heart represents a promising model for structure-function analyses. Rabbit hearts were subjected to an ex vivo perfusion protocol that achieves gene transfer in >90% of cardiac myocytes. Contractile function of isolated myocardial preparations of these hearts was then observed for 2 days in a recently developed trabecula culture system. In sham-infected hearts, the initial developed force (F(init)) (15.6 +/- 3.7 mN/mm(2); n = 12) did not change significantly after 48 h (17.0 +/- 1.9 mN/mm(2); P = 0.46). In adenovirus-infected preparations, F(init) (14.3 +/- 1. 8 mN/mm(2); n = 21) did not significantly differ from the control (P = 0.75) and was unchanged after 48 h (15.3 +/- 2.5 mN/mm(2); P = 0. 93). After 2 days of continuous contractions, we observed homogenous and high-level expression of the reporter genes LacZ coding for beta-galactosidase and Luc coding for firefly luciferase. Luciferase activity increased more than 2,500-fold from background levels of 8. 7 x 10(3 )+/- 5.0 x 10(3) relative light units (RLU)/mg protein (from hearts transfected with promotorless adenovirus with luciferase transgene construct AdNULLLuc, n = 5) to 23.4 x 10(6)+/- 11.1 x 10(6)RLU/mg protein (from hearts tranfected with adenovirus with Rous sarcoma virus promotor and luciferase transgene construct AdRSVLuc, n = 5) in infected myocardial preparations (P < 0.005). Our results demonstrate a new ex vivo approach to achieve homogenous and high-level expression of recombinant adenoviral genes in contracting myocardium without adverse functional effects. 相似文献
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Toischer K Kochhäuser S Nguyen van P Leineweber K Hasenfuss G Kögler H 《FEBS letters》2012,586(9):1363-1369
Proteins are folded in the endoplasmic reticulum (ER). ER stress initially leads to compensatory upregulation of ER chaperones and later to apoptosis, but the contribution of biomechanical load vs. neurohumoral stress to myocardial ER stress is unknown. We show that the ER chaperones Grp78 and calreticulin (CRT) are upregulated by afterload, but not by preload in vitro and in vivo. Angiotensin II upregulated ER chaperones in unloaded muscle strips, but the angiotensin receptor-1 antagonist irbesartan did not significantly blunt the induction of ER chaperones by afterload. In monocrotaline-treated rats, Grp78 and CRT were upregulated in the afterloaded right ventricle, but not in the only neurohumorally stressed left ventricle. These findings suggest that afterload but not preload induces myocardial ER stress, largely independent of angiotensin II signaling. 相似文献
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I. Hasenfuss 《Zoomorphology》1997,117(3):155-164
The patterns of scolopal organs and their innervation were studied by the methylene blue method in larvae, pupae and adults
of an Yponomeuta species (Yponomeutidae) and of tympanate adult representatives of the Noctuoidea, Geometridae, Drepanidae and Pyraloidea.
The studies were focused mainly on the mesothorax, the metathorax and some anterior abdominal segments. In the abdominal tympanal
organs of Geometridae, Drepanidae and Pyraloidea, the auditory scolopidia are homologous with the lateral scolopal organs
of the first abdominal segment; however, the hearing organs as such evolved independently in the three taxa. The studies confirm
that the tympanal organ in the Noctuoidea is derived from the caudal dorsolateral region of the metathorax including its dorsal
scolopal organ and the B-cell. The adult scolopal organs are present already in the larvae and are maintained nearly unchanged
during metamorphosis to the adult. Only in the Noctuoidea are the three sensory cells of the larval scolopal organs, which
become part of the tympanal organs, reduced to one (in Notodontidae) or two (in other Noctuoidea) during metamorphosis. A
hypothetical scenario of the evolution of the tympanal organs is outlined.
Accepted: 12 March 1997 相似文献
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Holmes JW Hünlich M Hasenfuss G 《American journal of physiology. Heart and circulatory physiology》2002,283(1):H324-H330
We tested the hypothesis that economy and efficiency are independent of length in intact cardiac muscle over its normal working range. We measured force, force-time integral, force-length area, and myocardial oxygen consumption in eight isometrically contracting rabbit right ventricular papillary muscles. 2,3-Butanedione monoxime was used to partition nonbasal oxygen consumption into tension-independent and tension-dependent components. Developed force, force-time integral, and force-length area increased by factors of 2.4, 2.7, and 4.8, respectively, as muscle length was increased from 90% to 100% maximal length, whereas tension-dependent oxygen consumption increased only 1.6-fold. Economy (the ratio of force-time integral to tension-dependent oxygen consumption) increased significantly with muscle length, as did contractile efficiency, the ratio of force-length area to tension-dependent oxygen consumption. The average force-length area-nonbasal oxygen consumption intercept was more than the twice tension-independent oxygen consumption. We conclude that economy and efficiency increase with length in rabbit myocardium. This conclusion is consistent with published data in isolated rabbit and dog hearts but at odds with studies in skinned myocardium. 相似文献
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Gómez AM Schuster I Fauconnier J Prestle J Hasenfuss G Richard S 《American journal of physiology. Heart and circulatory physiology》2004,287(5):H1987-H1993
Ryanodine receptors/Ca2+-release channels (RyR2) from the sarcoplasmic reticulum (SR) provide the Ca2+ required for contraction at each cardiac twitch. RyR2 are regulated by a variety of proteins, including the immunophilin FK506 binding protein (FKBP12.6). FKBP12.6 seems to be important for coupled gating of RyR2 and its deficit and alteration may be involved in heart failure. The role of FKBP12.6 on Ca2+ release has not been analyzed directly, but rather it was inferred from the effects of immunophilins, such us FK506 and rapamycin, which, among other effects, dissociates FKBP12.6 from the RyR2. Here, we investigated directly the effects of FKBP12.6 on local (Ca2+ sparks) and global [intracellular Ca2+ concentration ([Ca2+]i) transients] Ca2+ release in single rat cardiac myocytes. The FKBP12.6 gene was transfected in single myocytes using the adenovirus technique with a reporter gene strategy based on green fluorescent protein (GFP) to check out the success of transfections. Control myocytes were transfected with only GFP (Ad-GFP). Rhod-2 was used as the Ca2+ indicator, and cells were viewed with a confocal microscope. We found that overexpression of FKBP12.6 decreases the occurrence, amplitude, duration, and width of spontaneous Ca2+ sparks. FK506 had diametrically opposed effects. However, overexpression of FKBP12.6 increased the [Ca2+]i transient amplitude and accelerated its decay in field-stimulated cells. The associated cell shortening was increased. SR Ca2+ load, estimated by rapid caffeine application, was increased. In conclusion, FKBP12.6 overexpression decreases spontaneous Ca2+ sparks but increases [Ca2+]i transients, in relation with enhanced SR Ca2+ load, therefore improving excitation-contraction coupling. 相似文献
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I. Hasenfuss 《Zoomorphology》1999,119(3):143-162
Adhesion to smooth surfaces by means of thin fluid lipid film was studied on living larvae of 71 species of Lepidoptera by
a simple ”light reflection method”. The method made it possible to localize exactly the sites of adhesion and to estimate
roughly the film thickness, within a certain range. Furthermore, it revealed the general presence of mobile lipid on the entire
insect surface. The observations on living larvae were complemented by comparative structural studies of the adhesive parts
with light and scanning electron microscopes on preserved specimens of 161 species. Specialized adhesive devices were found
in great diversity on larval legs and prolegs, especially in larvae living in the open air on their food plants. Two main
surface types of adhesive cuticle were found: (1) cuticle with a flexible smooth surface and (2) cuticle with very numerous
small projections (microtrichia) with spatulate and recurved apices. Both the functional implications of the adhesive cuticular
structure and the role of the adhesive fluid as well as the evolution of the adhesive devices are discussed. The adhesive
effect is due to ”capillary” or meniscus forces.
Accepted: 29 July 1999 相似文献
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Nana‐Maria Wagner Gunnar Brandhorst Frauke Czepluch Mareike Lankeit Christoph Eberle Sebastian Herzberg Vivien Faustin Joachim Riggert Michael Oellerich Gerd Hasenfuss Stavros Konstantinides Katrin Schäfer 《Obesity (Silver Spring, Md.)》2013,21(3):461-468