Coenzyme A (
CoASH) is compartmentalized preferentially in the mitochondria, and
CoASH and its mixed
disulfide with
glutathione (
CoASSG) undergo
thiol/
disulfide exchange reactions with
glutathione (GSH) and
glutathione disulfide (
GSSG) in vitro. We measured
CoASH and
CoASSG in freeze-clamped lung tissues from Fischer-344 and Sprague-Dawley rats maintained in room air or exposed to >95% O(2) for 48 h to test the hypothesis that
oxidant stresses on lung
thiol status would be observed in the
CoASH/
CoASSG redox couple, suggesting
oxidant stress responses in the mitochondria. Lung tissue concentrations of
CoASSG in the Fischer-344 rats declined from 0.89 +/- 0.15 to 0.51 +/- 0.13 nmol/g of lung after 48 h of
hyperoxia.
CoASH levels declined from 6.40 +/- 0.84 to 3.0 +/- 0.65 nmol/g of lung, and
acetyl CoA levels also were lower in the lungs of animals exposed to
hyperoxia.
CoASH/
CoASSG ratios were lower in animals exposed to
hyperoxia, satisfying our previously defined criteria for an
oxidant stress on this
thiol/
disulfide redox couple, but absolute
CoASSG levels were not increased, as would be expected for
oxidant stresses driven simply by increases in
reactive oxygen species or other
oxidants.
Pulmonary edema was observed in the hyperoxic rats and accounted for some of the declines in
CoASH concentrations, but
CoASH contents per total lung also declined. Lung mitochondrial
succinate dehydrogenase activities were not diminished in rats exposed to
hyperoxia, indicating that the decreases in
CoASH concentrations are not attributable to general destruction of lung mitochondria. Lung
GSSG contents were greater in the
hyperoxia animals, but GSH/
GSSG ratios, which are dominated by extramitochondrial pools, did not decrease in these animals. The mechanisms responsible for, and the possible pathophysiologic consequences of, the decreases in lung
CoASH concentrations are not evident from the data available at the present time, but the loss of more than half the tissue contents of
CoASH is likely to generate additional metabolic effects that could have significant pathophysiologic consequences.