Leukotoxin, 9, 10-epoxy-12-octadecenoate inhibits mitochondrial
respiration of isolated perfused rat lung.
Sakai, Tetsuo, Takeshi Ishizaki, Teiji Ohnishi, Fumihiko Sasaki,
Shingo Ameshima, Tsuguhiko Nakai, Susumu Miyabo, Shigeru Matsukawa,
Mika Hayakawa, and Takayuki Ozawa.
Third Department of Internal Medicine, Fukui Medical School, Fukui
910-11, Japan, Central Research Laboratories, Fukui Medical School,
Fukui 910-11, Japan, Department of Biomedical Chemistry, Faculty of
Medicine, University of Nagoya, Nagoya 466, Japan
APStracts 2:0068L, 1995.
To investigate how mitochondrial function was affected in leukotoxin
(Lx)-, 9, 10-epoxy-12-octadecenoate-induced lung injury, lung
mitochondria were extracted from isolated perfused rat lung with or
without Lx-induced edematous injury. In the lung treated with 30
[mu]mol of Lx, the mitochondrial respiration rate in state 3 and 4
significantly decreased (without mitochondrial uncoupling)
concomitantly with increased release of LDH, a parameter for cellular
damage, into the perfusate and decreased ATP content in the lung
tissue compared to those of untreated lung. Moreover, 30 [mu]mol of
Lx resulted in significant inhibition of cytochrome c oxidase
activity (vs. vehicle control). In contrast, lower doses of Lx (10
[mu]mol) caused lung edema and cellular damage without evidence for
mitochondrial dysfunction. We also examined cellular and
mitochondrial damage in hydrostatic lung edema. Such edema showed
neither suppressed mitochondrial respiration nor elevated LDH
activity in perfusate, although lung wet weight is increased as much
as it did after 30 [mu]mol Lx treatment. Our results suggest that the
ex vivo mitochondrial dysfunction is one of the secondary (vs.
initial augmented permeability) but specific manifestations of
toxicity of Lx, and together with the previous reports, the ex vivo
damaging effect of Lx against mitochondria may be ascribed not to its
direct action on mitochondria but to Lx-derived cellular mechanism
(s).
Received 31 October 1994; accepted in final form 17 April 1995.
APS Manuscript Number L311-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 2 May 1995.