uncoupling of electron transport- elektroninsiirtoketjun poiskytkeytymä
Am J Physiol Lung Cell Mol Physiol. 2003 Feb;284(2):L298-306. Epub 2002 Oct 25.
Delta 9-tetrahydrocannabinol disrupts mitochondrial function and cell energetics.
Abstract
We have observed rapid and extensive depletion of cellular energy stores by Delta(9)-tetrahydrocannabinol
(THC) in the pulmonary transformed cell line A549. ATP levels declined
dose dependently with an IC(50) of 7.5 microg/ml of THC after 24-h
exposure. Cell death was observed only at concentrations >10
microg/ml. Studies using JC-1, a fluorescent probe for mitochondrial
membrane potential, revealed diminished mitochondrial function at THC
concentrations as low as 0.5 microg/ml. At concentrations of 2.5 or 10
microg/ml of THC, a decrease in mitochondrial membrane potential was
observed as early as 1 h after THC exposure. Mitochondrial function
remained diminished for at least 30 h after THC exposure. Flow cytometry
studies on cells exposed to particulate smoke extracts indicate that
JC-1 red fluorescence was fivefold lower in cells exposed to marijuana
smoke extract relative to cells exposed to tobacco smoke extract.
Comparison with a variety of mitochondrial inhibitors demonstrates that
THC produced effects similar to that of carbonyl cyanide
p-trifluoromethoxyphenylhydrazone, suggesting uncoupling of electron
transport. Loss of red JC-1 fluorescence by THC was suppressed by
cyclosporin A, suggesting mediation by the mitochondrial permeability
transition pore. This disruption of mitochondrial function was sustained
for at least 24 h after removal of THC by extensive washing. These
results suggest that exposure of the bronchopulmonary epithelium to THC
may have important health and physiological consequences.
Inga kommentarer:
Skicka en kommentar