Nov 15, 1989

Inhibition of cellular activities by triethyllead. Role of glutathione and accumulation of triethyllead in vitro

Biochemical Pharmacology
K MünterC Stournaras

Abstract

We investigated the interaction of triethyllead with ATP-coupled cellular enzymatic activities and the role of GSH to reverse the observed inhibition of these enzymes. Triethyllead inhibited the membrane bound Na+-K+-ATPase from HeLa cells (IC50 12 microM) and the ATP-hydrolysing activity of the mitochondrial F0-F1-ATPase complex (IC50 17 microM). Addition of 1 mM GSH reversed both enzyme activities totally, whereas lower GSH concentrations showed a less pronounced effect. Surprisingly, in freshly isolated rat liver mitochondria the ATP-synthesizing activity was also inhibited by triethyllead (IC50 16 microM), in spite of a measured high intramitochondrial GSH concentration (up to 10 mM). Further experiments in isolated submitochondrial particles revealed that ATP-synthesis and ATP-hydrolysis were inhibited by triethyllead with similar IC50 values, and both activities could be protected in vitro from the organolead compound in the presence of 1 mM GSH. Thus in all activities tested in vitro a high excess of GSH over triethyllead (greater than or equal to 25-fold) is necessary to restore the inhibited enzymes. The intramitochondrial triethyllead concentration was further determined after incubation of intact mitochondria with 10...Continue Reading

Mentioned in this Paper

Triethyllead hexafluorosilicate (-2)
F1-ATPase
Enzymes, antithrombotic
Adenosine Triphosphatases
August Rats
Organometallic Compounds
Mitochondria, Liver
Triethyllead
Glutathione Measurement
Mitochondria

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