Expression and distribution of Src in the nucleus of myocytes in cardiac hypertrophy.

The Src kinase is involved in signaling events leading to cardiac hypertrophy. The exact effects of tyrosine phosphorylation and subnuclear distribution on cardiac hypertrophy and failure remain to be investigated. In this study, we examined the intranuclear expression and distribution of c-Src, Src phosphorylated at tyrosine 529 (Src[pY529]), Src phosphorylated at tyrosine 418 (Src[pY418]) and Src phosphorylated at tyrosine 215 (Src[pY215]) in the myocardial nuclei of the left ventricle (LV) from 2-, 6-, 12- and 18-month-old spontaneously hypertensive heart failure (SHHF) rats and age-matched Wistar-Kyoto (WKY) rats as normotensive controls by western blot analysis, immunofluorescent labeling and immunoprecipitation. Cellular Src (c-Src) expression in the myocardial nuclei of the LV of the 2-, 6-, 12- and 18-month-old SHHF rats was not significantly different from that in the myocardial nuclei of the LV of the age-matched WKY rats. Although there were no significant differences observed between the levels of Src[pY529] and Src[pY418] in the myocardial nuclei of the LV of the 2-month-old SHHF and WKY rats, the expression of Src[pY529] significantly decreased, while that of Src[pY418] significantly increased in the myocardial nuclei of the LV of the 6-, 12- and 18-month-old SHHF rats compared to the age-matched WKY controls. Furthermore, as demonstrated by double labeling with antibodies against fibrillarin and Src-associated in mitosis 68 kDa (Sam68), c-Src was co-localized with both Sam68 and fibrillarin in the nuclei; Src[pY529] co-localized with fibrillarin, but Src[pY418] co-localized with Sam68. The results from the present study suggest that the dephosphorylation of Src tyrosine kinase 529, the phosphorylation of tyrosine 418 and their subnuclear redistribution are involved in endonuclear signal transduction in cardiac myocytes, which regulates the development and progression of LV eccentric hypertrophy induced by hypertension.