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Phosphorylation of Akt/GSK-3β/eNOS Amplifies 5-HT2B Receptor Blockade Mediated Anti-Hypertrophic Effect in Rats

Phosphorylation of Akt/GSK-3β/eNOS Amplifies 5-HT2B Receptor Blockade Mediated Anti-Hypertrophic Effect in Rats

Saurabh Bharti, Ratnakar Singh, S S Chauhan, Tajamul Hussain, Omar S Al-Attas, Dharamvir Singh Arya

FEBS Lett. 2012 Jan 20;586(2):180-5.

PMID: 22210189

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP152239468	SB 204741		152239-46-8	Price

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