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Coumaric acid induces mitochondrial damage and oxidative-mediated cell death of human endothelial cells

Posadino, Anna Maria and Cossu, Annalisa and Giordo, Roberta and Zinellu, Angelo and Sotgia, Salvatore and Vardeu, Antonella and Hoa, Phu Thi and Deiana, Luca and Carru, Ciriaco and Pintus, Gianfranco (2013) Coumaric acid induces mitochondrial damage and oxidative-mediated cell death of human endothelial cells. Cardiovascular toxicology, Vol. 13 (3), p. 301-306. eISSN 1559-0259. Article.

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DOI: 10.1007/s12012-013-9205-3


Evidence that higher natural antioxidants (NA) intake provides cardiovascular protection is contradictory. The endothelium plays a pivotal role in cardiovascular homeostasis, and for this reason, the molecular events resulting from the interaction of NA with endothelial cells (ECs) are actively investigated. Here, we show that moderately high doses of coumaric acid (CA) induced intracellular reactive oxygen species (ROS) production, mitochondrial membrane depolarization and ECs death. Treatment of ECs with cyclosporine A, a mitochondrial permeability transition pore inhibitor, prevented the oxidative-mediated cell damage indicating mitochondrial involvement in CA-induced ECs impairment. CA-induced intracellular ROS generation was counteracted by the specific cytochrome P450 (CYP) 2C9 inhibitor sulfaphenazole (SPZ). SPZ also prevented CA-induced mitochondrial membrane depolarization and ECs death, implicating CYP2C9 in mediating the cellular response upon CA treatment. Our results indicate that moderately high doses of CA can promote CYP2C9-mediated oxidative stress eliciting mitochondrial-dependent ECs death and may pave the way toward mechanistic insight into NA effects on cardiovascular cells.

Item Type:Article
ID Code:8936
Uncontrolled Keywords:Coumaric acid, endothelial cells, pro-oxidant effect, cell damage, mitochondria
Subjects:Area 05 - Scienze biologiche > BIO/10 Biochimica
Area 05 - Scienze biologiche > BIO/12 Biochimica clinica e biologia molecolare clinica
Divisions:001 Università di Sassari > 02 Centri > Centro di eccellenza interdisc. sviluppo ricerca biotecnologica e studio biodiversità della Sardegna e dell'area mediterranea
001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
Publisher:Humana Press
Copyright Holders:© Springer Science+Business Media New York 2013
Deposited On:26 Apr 2013 11:00

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