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Toxicity of emestrin, a new macrocyclic dithiodioxopiperazine mycotoxin, to mitochondrial function

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Abstract

The effect of emestrin, a new macrocyclic epidithiodioxopiperazine mycotoxin from severalEmericella species, on mitochondrial reactions was studied using isolated rat liver mitochondria to gain insight into the molecular mechanism for itsin vivo toxicity to rat and mouse. Emestrin was found to inhibit ATP synthesis in mitochondria causing an uncoupling of oxidative phosphorylation and a depression of respiration in isolated mitochondria. In addition to these effects on mitochondrial respiration, emestrin elicited a dratsic structural alteration (swelling) of mitochondria as observed in thein vivo system. The mitochondrial swelling was significantly enhanced by the subsequent addition of calcium ion. Emestrin B, in which dithio group is replaced by trithio group, exerted an uncoupling effect on oxidative phosphorylation without accompanying such depressive effect on state 3 respiration as observed for emestrin.

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References

  1. Sey H, Nakajima S, Kawai K, and Udagawa S (1985) Structure and absolute configuration of emestrin, a new macrocyclic epidithiodioxopiperazine fromEmericella striata. J Chem Soc Chem Commun 657–658

  2. Yamazaki Y (1985) Personal communication

  3. Terao T, Ito E, Udagawa S, Kawai K, Nozawa K (1988) Acute intoxication induced by emestrin, a new mycotoxin fromEmericella species. Proc Jpn Mycotoxicol 27:31–32

    CAS  Google Scholar 

  4. Kawai K, Nakamaru T, Maebayashi H, Nozawa Y, and Yamazaki M (1983) Inhibition by secalonic acid D of oxidative phosphorylation and Ca++-induced swelling in mitochondria from rat livers. Appl Environ Microbiol 46:793–796

    CAS  PubMed  Google Scholar 

  5. Kawai K, Mori H, and Kitamura J (1983) The uncoupling effect of flavoglaucin, a benzoquinol mycotoxin fromAspergillus chevalieri, on mitochondrial respiration. Toxicol Lett 19:321–325

    Article  CAS  PubMed  Google Scholar 

  6. Kawai K, Nozawa Y, Maebayashi Y, Yamazaki M, and Hamasaki T (1984) Averufin, an anthraquinoid mycotoxin possessing a potent uncoupling effect on mitochondrial respiration. Appl Environ Microbiol 47:481–483

    CAS  PubMed  Google Scholar 

  7. Kawai K, Nakamaru T, Nozawa Y, Maebayashi Y, Yamazaki M, and Natori S (1984) The inhibitory effect of sterigmatocystin and 5,6-dimethoxysterigmatocystin on ATP synthesis in mitochondria. Appl Environ Microbiol 48:1001–1003

    CAS  PubMed  Google Scholar 

  8. Kawai K, Shiojiri H, Nakamaru T, Nozawa Y, Sugie S, Mori H, Kato T, and Ogihara Y (1985) Cytotoxicity and genotoxicity of xenoclauxin and desacetylduclauxin fromPenicillium duclauxii (Delacroix). Cell Biol Toxicol 1:1–10

    Article  CAS  PubMed  Google Scholar 

  9. Schneider WC (1948) Intracellular distribution of enzymes. The oxidation of octanoic acid by rat liver fractions. J Biol Chem 176:259–266

    CAS  PubMed  Google Scholar 

  10. Chance B and Williams GR (1956) The respiratory chain and oxidative phosphorylation. Advances in Enzymology 17:65–134

    CAS  Google Scholar 

  11. Tedeschi H and Harris DL (1955) The osmotic behavior and permeability to non-electrolytes of mitochondria. Arch Biochem Biophys 58:52–67

    Article  CAS  PubMed  Google Scholar 

  12. Lowry OH, Rosebrough AL, Farr AL, and Randall RJ (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  13. Ishizaki K, Kawai K, Nakamaru T, Hisada K, Nozawa Y, and Kawai K (1988) Inhibition of mitochondrial respiration by emestrin, a new mycotoxin fromEmericella species. Proc Jpn Mycotoxicol 28: in press

  14. Wojtczak L and Lehninger AL (1961) Formation and disappearance of an endogenous uncoupling factor during swelling and contraction of mitochondria. Biochim Biophys Acta 51:442–456

    Article  CAS  PubMed  Google Scholar 

  15. Mitchell P (1977) Chemiosmotic coupling in oxidative and photosynthetic phosphorylation. Biol Rev 41:445–502

    Article  Google Scholar 

  16. McLaughlin SGA and Dilger JP (1980) Transport of protons across membranes by weak acids. Physiol Rev 60:825–863

    CAS  PubMed  Google Scholar 

  17. Terada H (1981) The interaction of highly active uncouplers with mitochondria. Biochim Biophys Acta 630:225–242

    Google Scholar 

  18. 18 Van Dam K (1967) The inhibitory effect of uncouplers of oxidative phosphorylation of mitochondrial respiration. Biochim Biophys Acta 131:407–411

    Article  PubMed  Google Scholar 

  19. Wilson DF and Merz RD (1967) Inhibition of mitochondrial respiration by uncouplers of oxidative phosphorylation. Arch Biochem Biophys 119:470–567

    Article  CAS  PubMed  Google Scholar 

  20. Papa S, Lofrumento NE, Paradies G, and Quagliello E (1969) Biochim Biophys Acta 180:35–44

    Article  CAS  PubMed  Google Scholar 

  21. Lehninger AL (1962) Water uptake and extrusion by mitochondria in relation to oxidative phosphorylation. Physiol Rev 42:467–517

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Faculty of Home Economics, Chukyo Women’s University, Ohbu 474, Aichi, Japan

    Kawai K & Ishizaki K

  2. Department of Biochemistry, Gifu University School of Medicine, 500, Gifu, Japan

    Nakamaru T, Hisada K & Nozawa Y

  3. Faculty of Pharmaceutical Science, Hoshi University, 142, Tokyo, Japan

    Kawai K-I

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  1. Kawai K
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  2. Ishizaki K
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  3. Nakamaru T
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  4. Hisada K
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  5. Nozawa Y
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  6. Kawai K-I
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Kawai, K., Ishizaki, K., Nakamaru, T. et al. Toxicity of emestrin, a new macrocyclic dithiodioxopiperazine mycotoxin, to mitochondrial function. Mycotox Res 5, 2–8 (1989). https://doi.org/10.1007/BF03192110

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  • DOI: https://doi.org/10.1007/BF03192110

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