Effects of different small HSPB members on contractile dysfunction and structural changes in a Drosophila melanogaster model for Atrial Fibrillation

Autor: Lei Ke, Johannes J. L. van der Want, Bianca J. J. M. Brundel, Robert M. Tanguay, Geneviève Morrow, Ody C. M. Sibon, Harm H. Kampinga, Katarina Mackovicova, Robert H. Henning, Deli Zhang
Přispěvatelé: Physiology, Groningen University Institute for Drug Exploration (GUIDE), Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP), Groningen Kidney Center (GKC), Groningen Institute for Organ Transplantation (GIOT)
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Zdroj: Journal of Molecular and Cellular Cardiology, 51(3), 381-389
Journal of Molecular and Cellular Cardiology, 51(3), 381-389. Academic Press Inc.
Journal of Molecular and Cellular Cardiology 51 (2011) 3
Zhang, D, Ke, L, Mackovicova, K, Van Der Want, J J L, Sibon, O C M, Tanguay, R M, Morrow, G, Henning, R H, Kampinga, H H & Brundel, B J J M 2011, ' Effects of different small HSPB members on contractile dysfunction and structural changes in a Drosophila melanogaster model for Atrial Fibrillation ', Journal of Molecular and Cellular Cardiology, vol. 51, no. 3, pp. 381-389 . https://doi.org/10.1016/j.yjmcc.2011.06.008
Journal of molecular and cellular cardiology, 51(3), 381-389. ELSEVIER SCI LTD
ISSN: 0022-2828
DOI: 10.1016/j.yjmcc.2011.06.008
Popis: The most common clinical tachycardia, Atrial Fibrillation (AF), is a progressive disease, caused by cardiomyocyte remodeling, which finally results in contractile dysfunction and AF persistence. Recently, we identified a protective role of heat shock proteins (HSPs), especially the small HSPB1 member, against tachycardia remodeling in experimental AF models. Our understanding of tachycardia remodeling and anti-remodeling drugs is currently hampered by the lack of suitable (genetic) manipulatable in vivo models for rapid screening of key targets in remodeling. We hypothesized that Drosophila melanogaster can be exploited to study tachycardia remodeling and protective effects of HSPs by drug treatments or by utilizing genetically manipulated small HSP-overexpressing strains. Tachypacing of Drosophila pupae resulted in gradual and significant cardiomyocyte remodeling, demonstrated by reduced contraction rate, increase in arrhythmic episodes and reduction in heart wall shortening, compared to normal paced pupae. Heat shock, or pretreatment with HSP-inducers GGA and BGP-15, resulted in endogenous HSP overexpression and protection against tachycardia remodeling. DmHSP23 overexpressing Drosophilas were protected against tachycardia remodeling, in contrast to overexpression of other small HSPs (DmHSP27, DmHSP67Bc, DmCG4461, DmCG7409, and DmCG14207). (Ultra)structural evaluation of the tachypaced heart wall revealed loss of sarcomeres and mitochondrial damage which were absent in tachypaced DmHSP23 overexpressing Drosophila. In addition. tachypacing induced a significant increase in calpain activity, which was prevented in tachypaced Drosophila overexpressing DmHSP23. Tachypacing of Drosophila resulted in cardiomyocyte remodeling, which was prevented by general HSP-inducing treatments and overexpression of a single small HSP, DmHSP23. Thus, tachypaced D. melanogaster can be used as an in vivo model system for rapid identification of novel targets to combat AF associated cardiomyocyte remodeling. (C) 2011 Elsevier Ltd. All rights reserved.
Databáze: OpenAIRE
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