Evidence for disruption of sphingolipid metabolism as a contributing factor in the toxicity and carcinogenicity of fumonisins

R. T. Riley, E. Wang, J. J. Schroeder, E. R. Smith, R. D. Plattner, N. Abbas, H. S. Yoo, A. H. Merrill

Research output: Contribution to journalReview articlepeer-review

149 Scopus citations

Abstract

Fumonisins are inhibitors of the biosynthesis of sphingosine and more complex sphingolipids. In eucaryotic cells, fumonisin inhibition of sphingolipid biosynthesis is a result of inhibition of the enzyme ceramide synthase. Large increases in free sphinganine concentration in plant and animal cells are observed within a few hours after exposure to fumonisins and/or Alternaria toxins (AAL-toxins). Some of the sphinganine is metabolized to other bioactive intermediates, and some is released from cells. In animals, free sphinganine accumulates in tissues and quickly appears in blood and urine. Free sphingoid bases are toxic to most cells, and complex sphingolipids are essential for normal cell growth. Fumonisin B1 stimulates sphinganine-dependent DNA synthesis in Swiss 3T3 cells, but is mitoinhibitory in other cell types. In cultured cells the accumulation of bioactive long-chain sphingoid bases and depletion of complex sphingolipids are clearly contributing factors in growth inhibition, increased cell death, and (in Swiss 3T3 cells) mitogenicity of fumonisins. While disruption of sphingolipid metabolism directly affects cells, it may indirectly affect some tissues. For example, fumonisin B1 impairs the barrier function of endothelial cells in vitro. Adverse effects on endothelial cells could indirectly contribute to the neurotoxicity and pulmonary edema caused by fumonisins. It is hypothesized that fumonisin-induced changes in the sphingolipid composition of target tissues could directly or indirectly contribute to all Fusarium moniliforme-associated diseases.

Original languageEnglish (US)
Pages (from-to)3-15
Number of pages13
JournalNatural Toxins
Volume4
Issue number1
DOIs
StatePublished - 1996

Keywords

  • AAL-toxin
  • AAL-toxin
  • Carcinogenesis
  • Cytotoxicity
  • Fumonisins
  • Fusarium moniliforme
  • Phytotoxicty
  • Sphinganine
  • Sphingolipids

ASJC Scopus subject areas

  • Toxicology

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