Asenapine increases nitric oxide release and protects porcine coronary artery endothelial cells against peroxidation

Elena Grossini, Carla Gramaglia, Serena Farruggio, Kevin Bellofatto, Chiara Anchisi, David Mary, Giovanni Vacca, Patrizia Zeppegno

Research output: Contribution to journalArticle

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 (p2-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.

Original languageEnglish
Pages (from-to)127-141
Number of pages15
JournalVascular Pharmacology
Volume60
Issue number3
DOIs
Publication statusPublished - 2014

Keywords

  • Antipsychotic drugs
  • Apoptosis
  • Cell survival
  • Endothelium
  • Nitric oxide

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Physiology
  • Medicine(all)

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  • Cite this

    Grossini, E., Gramaglia, C., Farruggio, S., Bellofatto, K., Anchisi, C., Mary, D., Vacca, G., & Zeppegno, P. (2014). Asenapine increases nitric oxide release and protects porcine coronary artery endothelial cells against peroxidation. Vascular Pharmacology, 60(3), 127-141. https://doi.org/10.1016/j.vph.2014.01.008