1616 REYE'S SYNDROME SERA: EFFECT ON RESPIRATION

Abstract

The effect on the respiration of isolated rat liver mitochondria of sera from 6 patients in profound coma due to Reye's syndrome (R.S.) was assessed. Respiration was measured polarographically with 5 mg of mitochondrial protein. Active respiration was initiated with 3mM of glutamate and 0.1 mM ADP. 10λ of 5x concentrated control or R.S. serum was added to the resting state. R.S. serum initially produced a profound stimulation of respiration (5.65 ± 0.18 nmol O2/mg protein, control = 2.11 ± 0.15, p<0.0001) lasting 1-3 minutes with a slight increase in respiration thereafter. This effect was diminished but not ablated with the addition of 1 mM EgTA to the incubating medium. Increasing [EgTA] to 30 mM or adding 5 nmol ruthenium red to inhibit calcium uptake did not further diminish the initial stimulation of respiration. Stimulation by R.S. sera occurred in the presence of rotenone and antimycin, suggesting that the effect was beyond Site I and II in the respiratory chain. Respiration was also stimulated in the presence of rutamycin, suggesting that R.S. sera might transiently uncouple oxidative phosphorylation. These findings confirm Aprille's observations (Science 197:908, 1977) in part, except that the effect of R.S. sera on respiration was transient. Entry of calcium into the mitochondria plays some role in this phenomenon, but the principal effect appears to be secondary to a transient stimulant of respiration or a weak uncoupler of oxidative phosphorylation that is consumed or inactivated within 1-3 minutes.