title: Asenapine increases nitric oxide release and protects porcine coronary artery endothelial cells against peroxidation.
abstract: Changes in endothelial function and peroxidation could play a significant role in the pathophysiology of cardiovascular disease in psychiatric patients. In particular, endothelial nitric oxide (NO) could either exert a beneficial or detrimental effect depending on the involvement of NO synthase (NOS) subtype. Therefore, we planned to examine the effects of asenapine on NO release and protection against oxidative stress in porcine coronary endothelial cells (CEC). The Griess system and Western blot were used for NO detection and to examine changes in protein activation and expression. In addition, cell oxidative/antioxidant status and mitochondrial membrane potential were measured by specific fluorescent dyes. Asenapine caused a concentration-dependent increase of NO production (p<0.05) by the involvement of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA), phospholipase C (PLC), β2-adrenoceptor-related pathway, Akt, extracellular-signal-regulated kinases 1/2 (ERK1/2) and p38 mitogen-activated protein kinases (p38 MAPK). Furthermore, asenapine protected CEC against oxidative stress by preventing reactive oxygen species production and glutathione reduction, mitochondrial membrane potential collapse and apoptosis, and by modulation of the inducible NOS (iNOS). In conclusion, in CEC asenapine induced eNOS-dependent NO production through an intracellular signaling leading to Akt, ERK1/2 and p38MAPK activation. Moreover, asenapine protected CEC against oxidative stress by modulation of antioxidant system, apoptosis, cell survival signaling and mitochondria functioning.
authors: Lab. Physiology and Experimental Surgery, Psychiatric Unit, Dept. Translational Medicine, University Eastern Piedmont "A. Avogadro", Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carità, corso Mazzini 36, Novara, Italy. Electronic address: grossini@med.unipmn.it.
authors: Elena
authors: E
authors: Grossini
authors: Lab. Physiology and Experimental Surgery, Psychiatric Unit, Dept. Translational Medicine, University Eastern Piedmont "A. Avogadro", Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carità, corso Mazzini 36, Novara, Italy.
authors: Carla
authors: C
authors: Gramaglia
authors: Lab. Physiology and Experimental Surgery, Psychiatric Unit, Dept. Translational Medicine, University Eastern Piedmont "A. Avogadro", Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carità, corso Mazzini 36, Novara, Italy.
authors: Serena
authors: S
authors: Farruggio
authors: Lab. Physiology and Experimental Surgery, Psychiatric Unit, Dept. Translational Medicine, University Eastern Piedmont "A. Avogadro", Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carità, corso Mazzini 36, Novara, Italy.
authors: Kevin
authors: K
authors: Bellofatto
authors: Lab. Physiology and Experimental Surgery, Psychiatric Unit, Dept. Translational Medicine, University Eastern Piedmont "A. Avogadro", Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carità, corso Mazzini 36, Novara, Italy.
authors: Chiara
authors: C
authors: Anchisi
authors: Lab. Physiology and Experimental Surgery, Psychiatric Unit, Dept. Translational Medicine, University Eastern Piedmont "A. Avogadro", Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carità, corso Mazzini 36, Novara, Italy.
authors: David
authors: D
authors: Mary
authors: Lab. Physiology and Experimental Surgery, Psychiatric Unit, Dept. Translational Medicine, University Eastern Piedmont "A. Avogadro", Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carità, corso Mazzini 36, Novara, Italy.
authors: Giovanni
authors: G
authors: Vacca
authors: Lab. Physiology and Experimental Surgery, Psychiatric Unit, Dept. Translational Medicine, University Eastern Piedmont "A. Avogadro", Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carità, corso Mazzini 36, Novara, Italy.
authors: Patrizia
authors: P
authors: Zeppegno
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D003986:Dibenzocycloheptenes; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013552:Swine
chemical_list: D002316:Cardiotonic Agents; D003986:Dibenzocycloheptenes; D006576:Heterocyclic Compounds, 4 or More Rings; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C522667:asenapine
keywords: Antipsychotic drugs; Apoptosis; Cell survival; Endothelium; Nitric oxide