Document Detail


A microelectrode-based sensor for label-free in vitro detection of ischemic effects on cardiomyocytes.
MedLine Citation:
PMID:  19285854     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Heart diseases represent the most common cause of death in industrialised countries. For this reason target identification and development of novel anti-target drugs are in the focus of pharmaceutical industry. Especially cardiac infarct is a topical field of research. A bottleneck in today's long-duration and high-cost drug development is the lack of fast, label-free and cell-based high throughput/high content screening (HTS/HCS) assays for bridging the gap between cell-free screening and animal experiments. Here, we report for the first time on an in vitro cardiac ischemic model, where pathological consequences of simulated cardiac infarct can be detected quantitatively by microelectrode array-based impedance spectroscopy. Using the contractile HL-1 cell line and defined ischemic conditions we were able to develop a standardised and reproducible pathologic model. We characterised and verified the HL-1 based ischemic model by apoptosis and proliferation assays as well as immunochemical analysis of cell-cell junctions. We showed that the observed cell and biomolecular effects correspond with results obtained by impedance spectroscopy. Functionality of the impedimetric assay was demonstrated by real-time detection of reduced pathological effects due to application of the selective Rac1 inhibitor NCS23766. Numerical analysis by means of an equivalent circuit allowed the quantification of changes in resistance and capacitance of the adherent cell layer after ischemic treatment and application of NSC23766 as drug model. Our findings provide a novel cell-based real-time screening system for testing drug candidates against cardiac infarct and its implications.
Authors:
Dana Krinke; Heinz-Georg Jahnke; Oliver Pänke; Andrea A Robitzki
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-20
Journal Detail:
Title:  Biosensors & bioelectronics     Volume:  24     ISSN:  1873-4235     ISO Abbreviation:  Biosens Bioelectron     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-20     Completed Date:  2009-07-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9001289     Medline TA:  Biosens Bioelectron     Country:  England    
Other Details:
Languages:  eng     Pagination:  2798-803     Citation Subset:  IM    
Affiliation:
Centre for Biotechnology and Biomedicine (BBZ), University of Leipzig, Division of Molecular Biological-Biochemical Processing Technology, Deutscher Platz 5, 04103 Leipzig, Germany.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis
Biosensing Techniques / instrumentation*,  methods
Cell Line
Cell Proliferation
Electrochemistry / methods*
Humans
Intercellular Junctions / pathology
Ischemia / chemically induced,  diagnosis*
Microelectrodes*
Myocytes, Cardiac / pathology*
Spectrum Analysis / methods*
rac1 GTP-Binding Protein / antagonists & inhibitors,  metabolism
Chemical
Reg. No./Substance:
EC 3.6.5.2/rac1 GTP-Binding Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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