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Please use this identifier to cite or link to this item: http://ntour.ntou.edu.tw:8080/ir/handle/987654321/50938

Title: Cannabidiol induced apoptosis in human monocytes through mitochondrial permeability transition pore-mediated ROS production
Authors: Hsin-Ying Wu
Chung-Hsiung Huang
Yi-Hsuan Lin
Chia-Chi Wang
Tong-Rong Jan
Contributors: 國立臺灣海洋大學:食品科學系
Keywords: Apoptosis
Oxidative stress
Date: 2018-06
Issue Date: 2018-11-01T03:13:39Z
Publisher: Free Radical Biology and Medicine
Abstract: Abstract: Cannabidiol (CBD) has been reported to induce apoptosis in immune cells through oxidative stress-related mechanisms. The objective of the present study was to investigate the cellular mechanisms for CBD-induced apoptosis and oxidative stress in human monocytes. Exposure of freshly isolated human monocytes to CBD induced apoptosis in a time- and concentration-dependent manner. Time-course analyses revealed the induction of intracellular reactive oxygen species (ROS) at 1–2 h post CBD (16 μM) exposure. By comparison, the CBD treatment rapidly elicited the depolarization of mitochondrial membrane potential (MMP) within 5 min, and the oxidation of cardiolipin, a major lipid component of the mitochondrial inner membrane, within 15 min. Moreover, CBD induced the release of cytochrome c (Cyt c) from mitochondria. Mechanistic studies revealed that CBD-induced ROS production and apoptosis were not associated with the alteration of mitochondrial superoxide dismutase activity, the electron leakage through mitochondrial respiratory chain, and Fe2+- and Ca2+-mediated mechanisms. In contrast, CBD-induced apoptosis and MMP depolarization were markedly attenuated by the mitochondrial permeability transition pore (MPTP) inhibitor cyclosporin A (CsA), but not the calcineurin inhibitor FK506. Furthermore, CsA prevented cardiolipin oxidation and the MPTP opening induced by CBD. The present study suggests that CBD acts on the mitochondria to elicit ROS generation and apoptosis through MPTP opening and provides critical insights into the cellular mechanisms for CBD-induced oxidative stress in apoptotic monocytes.
Relation: 124 pp.311-318
URI: http://ntour.ntou.edu.tw:8080/ir/handle/987654321/50938
Appears in Collections:[食品科學系] 期刊論文

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