Analysis of fumonisin B1-induced apoptosis

Clinton Jones, Janice R. Ciacci-Zanella, Yange Zhang, Gail Henderson, Martin Dickman

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Abstract

Fumonisins are mycotoxins produced by Fusarium moniliforme, a prevalent fungus that infects corn and other cereal grains. Fumonisin B1 (FB1) is the most common mycotoxin produced by F. moniliforme, suggesting it has toxicologic significance. The structure of FB1 resembles sphingoid bases, and it inhibits ceramide synthase. Because sphingoid bases regulate cell growth, differentiation, transformation, and apoptosis, it is not surprising to find that FB1 can alter growth of certain mammalian cells. Previous studies concluded FB1-induced apoptosis, or cell cycle arrest, in African green monkey kidney fibroblasts (CV-1). In this study we have identified genes that inhibit FB1-induced apoptosis in CV-1 cells and two mouse embryo fibroblasts (MEF). A baculovirus gene, inhibitor of apoptosis (CpIAP), protected these cells from apoptosis. CpIAP blocks apoptosis induced by the tumor necrosis factor (TNF) pathway as well as other mechanisms. Further support for the involvement of the TNF signal transduction pathway in FB1-induced apoptosis was the cleavage of caspase 8. Inhibition of caspases by the baculovirus gene p35 also inhibited FB1-induced apoptosis. The tumor suppressor gene p53 was not required for FB1-induced apoptosis because p53-/- MEF undergo apoptosis following FB1 treatment. Furthermore, Bcl-2 was not an effective inhibitor of FB1-induced apoptosis in CV-1 cells or p53+/+ MEF. In summary, these results provide new information to help understand the mechanism by which FB1 induces apoptosis.

Original languageEnglish (US)
Pages (from-to)315-320
Number of pages6
JournalEnvironmental Health Perspectives
Volume109
Issue numberSUPPL. 2
Publication statusPublished - Jun 11 2001

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Keywords

  • Apoptosis
  • Fumonisin B
  • Mycotoxins
  • Signal transduction
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Cite this

Jones, C., Ciacci-Zanella, J. R., Zhang, Y., Henderson, G., & Dickman, M. (2001). Analysis of fumonisin B1-induced apoptosis. Environmental Health Perspectives, 109(SUPPL. 2), 315-320.