|
|||||
|
|
Cannabinoid receptor agonists are mitochondrial inhibitors: a unified hypothesis of how cannabinoids modulate mitochondrial function and induce cell death |
|
| Authors: | Athanasiou Andriani Clarke Anna B Turner Amy E Kumaran Nethia M Vakilpour Sara Smith Paul A Bagiokou Dimitra Bradshaw Tracey D Westwell Andrew D Fang Lin Lobo Dileep N Constantinescu Cris S Calabrese Vittorio Loesch Andrzej Alexander Stephen P H Clothier Richard H Kendall David A Bates Timothy E |
| Affiliation: | a School of Biomedical Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham NG7 2UH, UK b New Use Therapeutics Limited, BioCity Nottingham, Pennyfoot Street, Nottingham NG1 1GF, UK c School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK d Welsh School of Pharmacy, Cardiff University, Cardiff CF10 3XF, UK e Nottingham UK-China Collaboration on Complementary and Alternative Medicine (NUCCAM), School of Community Health Sciences, Division of Epidemiology and Public Health, University of Nottingham, Queen’s Medical Centre, Nottingham NG7 2UH, UK f School of Medical and Surgical Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham NG7 2UH, UK g Department of Chemistry, Biochemistry and Molecular Biology Section, Faculty of Medicine, University of Catania, Catania, Italy h Department of Anatomy and Developmental Biology, Royal Free & University College Medical School, UCL, Rowland Hill Street, London NW3 2PF, UK |
| Abstract: | Time-lapse microscopy of human lung cancer (H460) cells showed that the endogenous cannabinoid anandamide (AEA), the phyto-cannabinoid Δ-9-tetrahydrocannabinol (THC) and a synthetic cannabinoid HU 210 all caused morphological changes characteristic of apoptosis. Janus green assays of H460 cell viability showed that AEA and THC caused significant increases in OD 595 nm at lower concentrations (10-50 μM) and significant decreases at 100 μM, whilst HU 210 caused significant decreases at all concentrations. In rat heart mitochondria, all three ligands caused significant decreases in oxygen consumption and mitochondrial membrane potential. THC and HU 210 caused significant increases in mitochondrial hydrogen peroxide production, whereas AEA was without significant effect. All three ligands induced biphasic changes in either mitochondrial complex I activity and/or mitochondrial complex II-III activity. These data demonstrate that AEA, THC, and HU 210 are all able to cause changes in integrated mitochondrial function, directly, in the absence of cannabinoid receptors. |
| Keywords: | Cannabinoid Apoptosis Mitochondria Anandamide Δ-9-Tetrahydrocannabinol HU 210 |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ | |