Effects of the pyrrolizidine alkaloid senecionine and the alkenals trans-4-OH-hexenal and trans-2-hexenal on intracellular calcium compartmentation in isolated hepatocytes

Biochemical Pharmacology
D S Griffin, H J Segall

Abstract

The pyrrolizidine alkaloid senecionine has been shown to produce an increase in cytosolic free Ca2+ concentration in isolated hepatocytes that correlated with an increase in cellular toxicity. The cytotoxicity was greater in the absence of extracellular Ca2+ than in its presence, suggesting that alterations in intracellular Ca2+ distribution, and not an influx of extracellular Ca2+, were responsible for the senecionine-induced hepatotoxicity. The effect of senecionine, as well as the effects of trans-4-OH-2-hexenal (t-4HH), a microsomal metabolite of senecionine, and a related alkenal, trans-2-hexenal, on the sequestration of Ca2+ in mitochondrial and extramitochondrial compartments were examined in isolated hepatocytes. Each of the test compounds elicited a decrease in the available extramitochondrial Ca2+ stores that was inhibited by pretreatment with the thiol group reducing agent, dithiothreitol. Senecionine and t-4HH decreased the level of Ca2+ sequestered in the mitochondrial compartment of hepatocytes. The presence of a pyridine nucleotide reducing agent, beta-hydroxybutyrate, inhibited this reduction. These results suggest that both senecionine and t-4HH inhibit the sequestration of Ca2+ in extramitochondrial and mitoch...Continue Reading

References

Apr 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·A L LehningerE A Bababunmi
Jul 1, 1975·Zeitschrift Für Naturforschung. Section C: Biosciences·H EsterbauerN Scholz
Nov 9, 1979·Science·F A SchanneJ L Farber
Jul 1, 1971·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·I N White, A R Mattocks
Nov 1, 1966·The Biochemical Journal·R HemsH A Krebs
Nov 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·G BellomoS Orrenius
Sep 28, 1981·Life Sciences·J L Farber

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Citations

Apr 15, 1991·Biochemical Pharmacology·A PompellaM Comporti

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