TY - JOUR
T1 - Asenapine Effects On Peroxidation and Calcium Movements in HL-1 Cells
AU - Maria Cristina, RIZZA
AU - GROSSINI, Elena
AU - Isabella, COPPOLA
AU - Annalisa, ROSSI
AU - Eleonora, GAMBARO
AU - Eleonora, GATTONI
AU - Sarah, DI MARCO
AU - Serena, FARRUGGIO
AU - Giovanni, VACCA
AU - Gramaglia, Carla Maria
AU - ZEPPEGNO, Patrizia
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
Objectives 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
AB - 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.
Objectives 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
UR - https://iris.uniupo.it/handle/11579/71626
U2 - 10.1016/S0924-9338(15)32070-8
DO - 10.1016/S0924-9338(15)32070-8
M3 - Article
SN - 0924-9338
VL - 30
SP - 1603
JO - European Psychiatry
JF - European Psychiatry
ER -