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Involvement of cardiomyocyte apoptosis in myocardial injury of hereditary epileptic rats
- Source :
- Canadian Journal of Physiology and Pharmacology. 91:804-811
- Publication Year :
- 2013
- Publisher :
- Canadian Science Publishing, 2013.
-
Abstract
- Many clinical cases have been reported where epilepsy profoundly influenced the pathophysiological function of the heart; however, the underlying mechanisms were not elucidated. We use the tremor (TRM) rat as an animal model of epilepsy to investigate the potential mechanisms of myocardial injury. Cardiac functions were assessed by arrhythmia score, heart rate, heart:body mass ratio, and hemodynamic parameters including left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and maximum rate of left ventricular pressure rise and fall (+dp/dtmax and –dp/dtmax). Catecholamine level was detected by HPLC. Apoptotic index was estimated by TUNEL assay. The expressions of Bcl-2, Bax, caspase-3, extracellular signal-regulated protein kinase (ERK), c-Jun NH2-terminal protein kinases (JNK), and p38 were evaluated by Western blot. The results indicated that there existed cardiac dysfunction and cardiomyocyte apoptosis, accompanied by increasing catecholamine levels in TRM rats. Further investigation revealed that apoptosis was mediated by reducing Bcl-2, upregulating Bax, and activating caspase-3. Additional experiments demonstrated that P-ERK1/2 was decreased, whereas P-JNK and P-p38 were up-regulated. Our results suggest that the sympathetic nervous system activation and cardiomyocyte apoptosis are involved in the myocardial injury of TRM rats. The mechanisms of apoptosis might be associated with the activation of the mitochondria-initiated and the mitogen-activated protein kinase pathways.
- Subjects :
- Male
medicine.medical_specialty
Heredity
Heart Diseases
Physiology
Blotting, Western
Apoptosis
Bioinformatics
Rats, Inbred WKY
p38 Mitogen-Activated Protein Kinases
Ventricular Function, Left
Epilepsy
Catecholamines
Heart Rate
Physiology (medical)
Internal medicine
In Situ Nick-End Labeling
Ventricular Pressure
Animals
Medicine
Myocytes, Cardiac
Phosphorylation
Chromatography, High Pressure Liquid
bcl-2-Associated X Protein
Mitogen-Activated Protein Kinase 1
Pharmacology
Mitogen-Activated Protein Kinase 3
Caspase 3
business.industry
JNK Mitogen-Activated Protein Kinases
Stroke Volume
General Medicine
medicine.disease
Pathophysiology
Rats
Disease Models, Animal
Endocrinology
Proto-Oncogene Proteins c-bcl-2
Female
business
Cardiomyocyte apoptosis
Signal Transduction
Subjects
Details
- ISSN :
- 12057541 and 00084212
- Volume :
- 91
- Database :
- OpenAIRE
- Journal :
- Canadian Journal of Physiology and Pharmacology
- Accession number :
- edsair.doi.dedup.....03bb7c2ac2655cd3b96ec96e089e3d75
- Full Text :
- https://doi.org/10.1139/cjpp-2013-0005