PMID: 8460673Mar 1, 1993Paper

ATP synthase activity is required for fructose to protect cultured hepatocytes from the toxicity of cyanide

The American Journal of Physiology
J W SnyderJohn L Farber

Abstract

The contributions of the loss of the mitochondrial membrane potential (MMP) and a depletion of ATP to the genesis of lethal injury were evaluated in the killing of cultured hepatocytes by cyanide (CN). The glycolytic production of ATP from fructose (Fru) maintained the MMP and prevented the killing by CN. Inhibition of the mitochondrial ATP synthase by 0.1 micrograms/ml oligomycin (Oligo) reduced ATP stores at the same rate and to the same extent as did 1 mM CN. With Oligo there was no loss of the MMP, and the hepatocytes maintained viability over the 6 h during which CN killed all of the cells. Oligo had no effect on the rate of killing by CN. However, Oligo reversed the protective effect of Fru on CN-induced killing, a result that correlated with the loss of MMP but not with the depletion of ATP. Neither Fru nor Oligo affected the intracellular acidosis achieved with CN alone. Fru also prevented toxicity of the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP), a result that correlated with the preservation of MMP. Oligo potentiated the toxicity of CCCP. It is concluded that a functioning mitochondrial ATP synthase is required for the production of ATP from Fru to prevent the killing of hepatocytes by CN. The extent o...Continue Reading

References

Jan 1, 1976·Methods in Cell Biology·P O Seglen
Dec 1, 1988·Cell Calcium·A L NieminenJ J Lemasters
Jun 16, 1988·Biochemical and Biophysical Research Communications·D Di MonteM T Smith
Oct 1, 1981·Archives of Biochemistry and Biophysics·J L Farber, E E Young

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Citations

Oct 1, 1995·Journal of Biochemical Toxicology·A H HammondJ R Fry
Dec 1, 1994·Environmental Health Perspectives·J L Farber
Jan 1, 1997·Free Radical Biology & Medicine·F ValeriU A Boelsterli
Aug 26, 1998·Biochimica Et Biophysica Acta·F Di LisaV Petronilli
Jul 10, 2003·The Journal of Surgical Research·Andrey BelousRavi S Chari

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