Cannabinoid receptor agonists are mitochondrial inhibitors: a unified hypothesis of how cannabinoids modulate mitochondrial function and induce cell death

Athanasiou, Andriani and Clarke, Anna B. and Turner, Amy E. and Kumaran, Nethia M. and Vakilpour, Sara and Smith, Paul A. and Bagiokou, Dimitra and Bradshaw, Tracey D. and Westwell, Andrew D. and Fang, Lin and Lobo, Dileep N. and Constantinescu, Cris S. and Calabrese, Vittorio and Loesch, Andrzej and Alexander, Stephen P. H. and Clothier, Richard H. and Kendall, David A. and Bates, Timothy E. (2007) Cannabinoid receptor agonists are mitochondrial inhibitors: a unified hypothesis of how cannabinoids modulate mitochondrial function and induce cell death. Biochemical and Biophysical Research Communications, 364 (1). pp. 131-137. ISSN 0006-291x

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Full text URL: http://dx.doi.org/10.1016/j.bbrc.2007.09.107

Abstract

Time-lapse microscopy of human lung cancer (H460) cells showed that the endogenous cannabinoid anandamide (AEA), the phyto-cannabinoid Delta-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 microM) and significant decreases at 100 microM, 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.

Item Type:Article
Additional Information:Time-lapse microscopy of human lung cancer (H460) cells showed that the endogenous cannabinoid anandamide (AEA), the phyto-cannabinoid Delta-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 microM) and significant decreases at 100 microM, 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, Delta-9-tetrahydrocannabinol, anandamide, AEA, THC, HU 210, H460, apoptosis, mitochondria, hydrogen peroxide, mitochondrial membrane potential, mitochondrial complexes
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
B Subjects allied to Medicine > B140 Neuroscience
B Subjects allied to Medicine > B200 Pharmacology, Toxicology and Pharmacy
A Medicine and Dentistry > A300 Clinical Medicine
Divisions:College of Science > School of Life Sciences
ID Code:5210
Deposited By: Timothy Bates
Deposited On:26 Jun 2012 10:25
Last Modified:26 Jun 2012 10:25

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