Phosphorylation of Akt/GSK-3β/eNOS amplifies 5-HT2B receptor blockade mediated anti-hypertrophic effect in rats
, Bharti S, Singh R, Chauhan SS, Hussain T, Al-Attas OS, Arya DS. . 2012
Herein, we studied the cross talk between 5-HT(2B) receptor blocker (SB-204741) and GSK-3β inhibitor (SB-216763) in isoproterenol-induced cardiac hypertrophy for 28 days. SB-204741 treatment significantly ameliorated (P<0.05) myocardial dysfunction, myocyte area, fibrosis and myocardial architecture in isoproterenol insulted myocardium. Moreover, this improvement in functional and morphological changes was associated with suppression of hypertrophic (BNP and CK-MB), inflammatory (IKK-β/NF-κB/TNF-α and CRP), and apoptotic markers (TUNEL positivity and Bax expression) along with phosphorylation of Akt/GSK-3β/β-catenin/eNOS. Intriguingly, co-treatment with GSK-3β inhibitor (P<0.01) further amplified the anti-hypertrophic effect of SB-204741 (P<0.05) such that the effect was indistinguishable from that of vehicle treated rats. Thus, 5-HT(2B) receptor blockade mediated anti-hypertrophic effect is atleast in part is governed through phosphorylation of Akt/GSK-3β/β-catenin/eNOS via attenuating inflammatory and apoptotic pathways.
Abstract
Gestational diabetes mellitus (GDM) has been linked with adverse pregnancy outcomes. Vitamin D receptor (VDR) gene variants have been associated with diabetes mellitus susceptibility and related…
Abstract
Objectives: To assess circulating fetuin A and fetuin B levels in participants with and without Gestational Diabetes Mellitus (GDM) and to find out their correlations with other…