Investigation Of β-MHC And C-fos Gene Transcription Regulated By Nuclear CaM Ⅰ/CaMKⅡ-CaMKⅣ Signaling Pathway In Pressure Overload Rat Hearts

Cardiac hypertrophy is defined as an enlargement of heart associated with an increase in cardiac myocyte volume. The hypertrophy occurs in response to diverse pathophysiological stimuli such as hypertension, ischemic heart disease, valvular insufficiency, infection agents, or mutations in sarcomeric genes. Hypertrophic growth of myocardium is thought to preserve pump function, although prolongation of hypertrophic state is a leading predictor for development of arrhythmias, sudden death and heart failure. Many researches have indicated that myocardial hypertrophy might be triggered by Ca++ signal transduction. The current understanding of Ca++ in hypertrophic myocardium signaling mechanism has focused on cytoplasm Ca++, and the consequent activation of CaMⅠto Ca++/ CaMⅠ-regulated enzymes.CaMⅠand CaMK are involved in various cellular functions mediated by Ca++, such as transcriptional regulation, protein synthesis and release, ion channel function, cytoskeletal function, carbohydrate metabolism and so on. However the nucleus is the major site for regulation of gene expression in cardiac myocyte. It is unknown whether nuclear CaMⅠ/CaMKII-CaMKIV signaling are mediators for cardiac hypertrophy. This experiment is designed to clarify CaMⅠ/CaMKII-CaMKIV signaling molecular localization in myocardium, then explore their protein expression and activities during cardiac hypertrophy. Furthermore the relationship between CaMⅠ/CaMKII-CaMKIV signaling pathway andβ-MHC, c-fos gene expression was investigated.Methods1. The cardiac hypertrophy model of rat was prepared by transverse aortic coarctation (TAC). One hundred and fifty adult SD rats weighted 150-180g were randomly divided into two groups: sham-operated rats and TAC pressure-overload rats. The rats were restored to normal diets and room temperature for 4 weeks. The degree of left ventricle hypertrophy...