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Asenapine Effects On Peroxidation and Calcium Movements in HL-1 Cells

Published online by Cambridge University Press:  15 April 2020

M.C. Rizza ,
E. Grossini ,
I. Coppola ,
A. Rossi ,
E. Gambaro ,
E. Gattoni ,
S. Di Marco ,
S. Farruggio ,
G. Vacca  and
C. Gramaglia
...Show all authors
M.C. Rizza
Affiliation:
Department of Translational Medicine, Institute of Psychiatry University of Eastern Piedmont, Novara, Italy
E. Grossini
Affiliation:
Department of Translational Medicine, Lab. Physiology and Experimental Surgery, Novara, Italy
I. Coppola
Affiliation:
Department of Translational Medicine, Institute of Psychiatry University of Eastern Piedmont, Novara, Italy
A. Rossi
Affiliation:
Department of Translational Medicine, Institute of Psychiatry University of Eastern Piedmont, Novara, Italy
E. Gambaro
Affiliation:
Department of Translational Medicine, Institute of Psychiatry University of Eastern Piedmont, Novara, Italy
E. Gattoni
Affiliation:
Department of Translational Medicine, Institute of Psychiatry University of Eastern Piedmont, Novara, Italy
S. Di Marco
Affiliation:
Department of Translational Medicine, Institute of Psychiatry University of Eastern Piedmont, Novara, Italy
S. Farruggio
Affiliation:
Department of Translational Medicine, Lab. Physiology and Experimental Surgery, Novara, Italy
G. Vacca
Affiliation:
Department of Translational Medicine, Lab. Physiology and Experimental Surgery, Novara, Italy
C. Gramaglia
Affiliation:
Department of Translational Medicine, Institute of Psychiatry University of Eastern Piedmont, Novara, Italy
P. Zeppegno
Affiliation:
Department of Translational Medicine, Institute of Psychiatry University of Eastern Piedmont, Novara, Italy

Abstract

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Introduction

Bipolar patients are at higher risk for cardiovascular morbidity and mortality than their counterparts in the general population. In a recent in vitro study, Asenapine, a new antipsychotic for the treatment of mania/mixed mania, was found to keep physiological endothelial function by activation of eNOS-related NO release and to protect endothelial cells against peroxidation by interference with mitochondria, apoptosis and cell survival.

Objective

To examine the cardiac protective effects elicited by Asenapine against peroxidation and on the Ca2+ movements.

Methods

In HL-1 that had undergone oxidative stress by 20 min hydrogen peroxide the effects of 30 min pre-treatment with Asenapine on survival and proliferation will be examined. In Fura-2AM loaded HL-1 we will next analyze the effects of Asenapine on Ca2+ movements and the related involvement of cAMP/PKA and PLC pathways, CaMKII, L and T type Ca2+ channels and 5HT1A receptors. The role of ‘capacitative” Ca2+ entry, plasma-membrane Ca2+ pump inhibitor (PMCA) and Na+/Ca2+ exchanger will be analyzed. Changes of membrane potential caused by interference with K+ channels will be examined, as well.

Results

We expect to find a proliferative and anti-peroxidative effect of Asenapine in HL-1 cells. Asenapine could also affect Ca2+ movements through cAMP/PKA and PLC-dependent signalling and the involvement of 5HT1A receptors. The effects of Asenapine could also be related to changes of plasma membrane by interference with K+ channels and the modulation of PMCA activity and Na+/Ca2+ exchanger.

Conclusions

We expect to further confirm the protective effect of Asenapine against peroxidative injuries. Implications will be discussed

Type
Article: 1603
Information
European Psychiatry , Volume 30 , Issue S1: Abstracts of the 23rd European Congress of Psychiatry , March 2015 , pp. 1
Copyright
Copyright © European Psychiatric Association 2015
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