Document Detail


Relation between enzyme release and irreversible cell injury of the heart under the influence of cytoskeleton modulating agents.
MedLine Citation:
PMID:  9540843     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of agents modulating the cytoskeleton, taxol (microtubuli stabilizing), vinblastine (microtubuli destabilizing) and cytochalasin D (actin destabilizing) (10(-6) M each) on enzyme and ATP release as well as on irreversible cell injury were investigated in isolated perfused hypoxic and reoxygenated rat hearts. Enzyme (creatine kinase (CK)) and ATP concentration were assayed in the interstitial transudate and venous effluent. Irreversible cell injury was determined from trypan blue uptake and nuclear staining (NS) of cardiomyocytes in histologic sections. ATP release from nonneuronal cells was only detectable in the interstitial transudate and was not significantly altered by the agents. In controls total CK release (about 4% of total CK) exceeded the percentage of irreversibly injured cells by a factor of 8. Taxol and cytochalasin D abolished the hypoxia/reoxygenation induced interstitial CK release and reduced total CK release to a highly significant extent. The percentage of irreversible injured cells was even more diminished by these agents resulting in a ratio of CK/NS of 40. The effect of cytochalasin D apparently is the consequence of decreased contractile performance as shown by analogous depression by butonedione monoxine (BDM), whereas contractile activity was not altered by taxol. Vinblastine had no influence on CK release but increased the number of irreversibly injured cells significantly. In conclusion, cytoskeletal elements apparently participate in the hypoxia/reoxygenation induced process of release of cytosolic enzymes (CK) and irreversible injury in a different way and extent. Taxol exhibits a cytoprotective effect in isolated perfused rat hearts as evaluated by the extent of enzyme release and irreversible cell injury.
Authors:
E Skobel; H Kammermeier
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1362     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  1997 Dec 
Date Detail:
Created Date:  1998-04-21     Completed Date:  1998-04-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  128-34     Citation Subset:  IM    
Affiliation:
Institut für Physiologie der Medizinischen, Fakultät der RWTH Aachen, Universitätsklinikum, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Animals
Anoxia / metabolism
Creatine Kinase / metabolism
Cytochalasin D / pharmacology
Cytoskeleton / drug effects*
Female
Heart Rate
Myocardial Contraction / drug effects
Myocardial Reperfusion Injury / enzymology*,  pathology
Myocardium / enzymology*
Paclitaxel / pharmacology
Rats
Rats, Sprague-Dawley
Systole
Vinblastine / pharmacology
Chemical
Reg. No./Substance:
22144-77-0/Cytochalasin D; 33069-62-4/Paclitaxel; 56-65-5/Adenosine Triphosphate; 865-21-4/Vinblastine; EC 2.7.3.2/Creatine Kinase

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