Coumaric Acid Induces Mitochondrial Damage and Oxidative-Mediated Cell Death of Human Endothelial Cells

Abstract

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.

New Insights for Cellular and Molecular Mechanisms of Aging and Aging-Related Diseases: Herbal Medicine as Potential Therapeutic Approach

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ILEX PARAGUARIENSIS, EXERCISE AND CARDIOPROTECTION: A retrospective analysis

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p-Coumaric acid, a novel and effective biomarker for quantifying hypoxic stress by HILIC-ESI-MS

“…Q10 is an essential co-enzyme, localized at the inner membrane of mitochondria and has several important functions [36,37]. Firstly, Q10 is responsible for electron transfer between complexes I, II and III of the respiratory chain [39][40][41][42]. Secondly, Q10 represents an important proton carrier during this process; and thirdly, it is an important antioxidant for mitochondria under oxidative stress conditions [37,39].…”

“…Firstly, Q10 is responsible for electron transfer between complexes I, II and III of the respiratory chain [39][40][41][42]. Secondly, Q10 represents an important proton carrier during this process; and thirdly, it is an important antioxidant for mitochondria under oxidative stress conditions [37,39]. For those reasons, we interpret the increased amounts of p-coumaric acid during hypoxia as an indication of Q10 reduction (peak at 2.7 min).…”