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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-8-25
pubmed:abstractText
Previous in vivo study demonstrated that betagamma-CAT, a newly identified non-lens betagamma-crystallin and trefoil factor complex from frog Bombina maxima skin secretions, possessed potent lethal toxicity on mammals resulted from hypotension and cardiorespiratory arrest. However, the mechanism of cardiac dysfunction induced by the protein is unknown. Here, we report that betagamma-CAT, with dosages of 0.8-3.0 nM, elicited an acute negative inotropic effect in isolated rabbit heart Langendorff preparations, which mimicked acute heart failure. In addition, the effect of betagamma-CAT on the hearts was mediated by endothelium-dependent coronary vasoconstriction (P<0.01, compared between endothelium-intact and removal hearts). After betagamma-CAT (3.0 nM) treatment, the positive signal of tumor necrosis factor-alpha (TNF-alpha) was detected mainly around the endothelial cell layer as detected by in situ indirect immunofluorescence, indicating that the release of TNF-alpha occurred. At the same time, a rapid TNF-alpha release was detected in primary cultured rabbit endocardial endothelial cells (REECs) treated with betagamma-CAT. After addition of betagamma-CAT (3.0 nM) for 10 min and 30 min, the TNF-alpha levels were increased to 57.33+/-3.22 pg/ml and 60.00+/-5.35 pg/ml (P<0.05, compared with the control values of 21.67+/-3.45 pg/ml and 33.70+/-6.24 pg/ml, respectively). At high concentrations, betagamma-CAT interfered with the cell viability of REECs (CC(50) about 25 nM). Taken together, betagamma-CAT was able to induce acute myocardial depression and the toxic effect might be partially explained by the release of TNF-alpha. The finding provides new information to understand the patho-physiological roles of non-lens betagamma-crystallins and trefoil factors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0041-0101
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
285-92
pubmed:meshHeading
pubmed-meshheading:18602941-Acute Disease, pubmed-meshheading:18602941-Amino Acid Sequence, pubmed-meshheading:18602941-Animals, pubmed-meshheading:18602941-Anura, pubmed-meshheading:18602941-Cell Survival, pubmed-meshheading:18602941-Cells, Cultured, pubmed-meshheading:18602941-Crystallins, pubmed-meshheading:18602941-Disease Models, Animal, pubmed-meshheading:18602941-Dose-Response Relationship, Drug, pubmed-meshheading:18602941-Endothelial Cells, pubmed-meshheading:18602941-Endothelium, Vascular, pubmed-meshheading:18602941-Fluorescent Antibody Technique, Indirect, pubmed-meshheading:18602941-Heart, pubmed-meshheading:18602941-Heart Failure, pubmed-meshheading:18602941-Male, pubmed-meshheading:18602941-Membrane Proteins, pubmed-meshheading:18602941-Molecular Sequence Data, pubmed-meshheading:18602941-Myocardial Contraction, pubmed-meshheading:18602941-Peptides, pubmed-meshheading:18602941-Rabbits, pubmed-meshheading:18602941-Skin, pubmed-meshheading:18602941-Tumor Necrosis Factor-alpha
pubmed:year
2008
pubmed:articleTitle
Betagamma-CAT, a non-lens betagamma-crystallin and trefoil factor complex from amphibian skin secretions, caused endothelium-dependent myocardial depression in isolated rabbit hearts.
pubmed:affiliation
Biotoxin Units, Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, The Chinese Academy of Sciences, 32 East Jiao Chang Road, Kunming, Yunnan 650223, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't