Insulin-regulated protein kinases during postnatal development of rat heart

Abstract

The control of glucose uptake and glycogen metabolism by insulin in target organs is in part mediated through the regulation of protein-serine/threonine kinases. In this study, the expression and phosphotransferase activity levels of some of these kinases in rat heart ventricle were measured to investigate whether they might mediate the shift in the energy dependency of the developing heart from glycogen to fatty acids. Following tail-vein injection of overnight fasted adult rats with 2 U of insulin per kg body weight, protein kinase B (PKB), the 70-kDa ribosomal S6 kinase (S6K), and casein kinase 2 (CK2) were activated (30-600%), whereas the MAP/extracellular regulated kinases (ERK)1 and ERK2 were not stimulated under these conditions. When the expression levels of the insulin-activated kinases were probed with specific antibodies in ventricular extracts from 1-, 10-, 20-, 50-, and 365-day-old rats, phosphatidylinositol 3-kinase (PI3K), PKB, S6K, and CK2 were downregulated (40-60%) with age. By contrast, ventricular glycogen synthase kinase-3beta (GSK3beta) protein levels were maintained during postnatal development. Similar findings were obtained when the expression of these kinases was investigated in freshly isolated ventricular myocytes, where they were detected predominantly in the cytosolic fraction of the myocytes. Compared to other adult rat tissues such as brain and liver, the levels of PI3K, PKB, S6K, and GSK3beta were relatively low in the heart. Even though CK2 protein and activity levels were reduced by approximately 60% in 365 day as compared to 1-day-old rats, expression of CK2 in the adult heart was as high as detected in any of the other rat tissues. The high basal activities of CK2 in early neonatal heart may be associated with the proliferating state of myocytes.

Effects of Streptozocin Diabetes and Diabetes Treatment by Islet Transplantation on In Vivo Insulin Signaling in Rat Heart

“…MAPK phosphorylation was not stimulated by insulin and did not show differences in the experimental groups. The lack of insulin stimulation of MAPK is in agreement with a previous study, showing that in vivo injection of adult rats with insulin activates protein kinase B, p70S6K, and casein kinase 2 but not MAPK in the heart (30).…”

Ontogeny of phosphoinositide 3-kinase signaling in developing heart: effect of acute β-adrenergic stimulation

“…It has been shown that cardiac PI3K activity and level remain constant in postnatal animals from P1 to P20 (26). The cardiac PI3K activities in these animals, however, are significantly higher than those of adults.…”

Differential gene expression in infarct scar and viable myocardium from rat heart following coronary ligation

“…CK2, and especially the CK2 subunit, plays an important role in cell growth and proliferation [14] possibly via phosphorylation of histone deacetylase 2 (HDAC2) [15] [19] reported that endothelin-1 stimulates collagen accumulation at the site of infarction and ET-1 type A receptor antagonists have been shown to improve ventricular remodeling and survival in rats after infarction [20]. It will be interesting to test the effect of ET-1 on CK2 activity in normal heart as well as failing heart since CK2 proteins and activity in rat heart were reduced during development [21]. Thus CK2 may play an important role in the growth of cardiomyocytes and fibroblasts.…”