title: Involvement of cardiomyocyte apoptosis in myocardial injury of hereditary epileptic rats.
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.
authors.affiliation: a Department of Pharmacology, Harbin Medical University - Daqing, Daqing, Heilongjiang 163319, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Chen
authors.forename: Yong-gang
authors.initials: YG
authors.lastname: Cao
authors.forename: Han-ping
authors.initials: HP
authors.lastname: Qi
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.forename: Hong-li
authors.initials: HL
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002395:Catecholamines / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004827:Epilepsy / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006331:Heart Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006339:Heart Rate; D040941:Heredity; D020287:In Situ Nick-End Labeling; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D015398:Signal Transduction; D013318:Stroke Volume; D016277:Ventricular Function, Left; D017725:Ventricular Pressure; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D002395:Catecholamines; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D048031:JNK Mitogen-Activated Protein Kinases; C535149:Mapk1 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3