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Cannabidiol induced apoptosis in human monocytes through mitochondrial permeability transition pore-mediated ROS production.
Free Radic Biol Med. 2018 08 20; 124:311-318.FR

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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Wu HY
Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan; Laboratory Animal Center, National Health Research Institutes, Miaoli, Taiwan.
Huang CH
Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan; National Institute of Infectious Disease and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
Lin YH
Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
Wang CC
Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan; School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
Jan TR
Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: tonyjan@ntu.edu.tw.

MeSH

ApoptosisCannabidiolCells, CulturedHumansMembrane Potential, MitochondrialMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PoreMonocytesReactive Oxygen Species

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29940353

Citation

Wu, Hsin-Ying, et al. "Cannabidiol Induced Apoptosis in Human Monocytes Through Mitochondrial Permeability Transition Pore-mediated ROS Production." Free Radical Biology & Medicine, vol. 124, 2018, pp. 311-318.
Wu HY, Huang CH, Lin YH, et al. Cannabidiol induced apoptosis in human monocytes through mitochondrial permeability transition pore-mediated ROS production. Free Radic Biol Med. 2018;124:311-318.
Wu, H. Y., Huang, C. H., Lin, Y. H., Wang, C. C., & Jan, T. R. (2018). Cannabidiol induced apoptosis in human monocytes through mitochondrial permeability transition pore-mediated ROS production. Free Radical Biology & Medicine, 124, 311-318. https://doi.org/10.1016/j.freeradbiomed.2018.06.023
Wu HY, et al. Cannabidiol Induced Apoptosis in Human Monocytes Through Mitochondrial Permeability Transition Pore-mediated ROS Production. Free Radic Biol Med. 2018 08 20;124:311-318. PubMed PMID: 29940353.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabidiol induced apoptosis in human monocytes through mitochondrial permeability transition pore-mediated ROS production. AU - Wu,Hsin-Ying, AU - Huang,Chung-Hsiung, AU - Lin,Yi-Hsuan, AU - Wang,Chia-Chi, AU - Jan,Tong-Rong, Y1 - 2018/06/22/ PY - 2018/02/23/received PY - 2018/06/19/revised PY - 2018/06/21/accepted PY - 2018/6/26/pubmed PY - 2019/9/7/medline PY - 2018/6/26/entrez KW - Apoptosis KW - Cannabidiol KW - Mitochondrial KW - Monocyte KW - Oxidative stress SP - 311 EP - 318 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 124 N2 - 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. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/29940353/Cannabidiol_induced_apoptosis_in_human_monocytes_through_mitochondrial_permeability_transition_pore_mediated_ROS_production_ DB - PRIME DP - Unbound Medicine ER -