The mycotoxin fumonisin B1 inhibits eukaryotic protein synthesis: in vitro and in vivo studies

Mycopathologia. 2008 Jan;165(1):37-49. doi: 10.1007/s11046-007-9075-y. Epub 2007 Oct 30.

Abstract

Inhibitory action of Fumonisin B(1) (FB(1)) on eukaryotic protein synthesis was investigated, both in animal and plant system, and was compared with cycloheximide. Inhibitory effect of FB(1 )was monitored in the TCA precipitable proteins of rabbit reticulocyte lysates exposed to various concentrations of the mycotoxin (0.0013-2.76 mM), using (35) S-methionine as a tracer. FB(1) inhibited the protein synthesis by 6%, at 0.0013 mM and by 88%, at a higher concentration of 2.76 mM. Cycloheximide at a concentration of 0.355 mM was found to inhibit protein synthesis by 88%. Inhibitory action of FB(1) (1 mg kg(-1) body mass and a higher dose of 10 mg kg(-1) body mass) or cycloheximide (10 mg kg(-1) body mass; positive controls), injected intra-peritoneally into BALB/c mice was studied using (14)C-L: -Leucine as a tracer. FB(1) at lower dose of 1 mg kg(-1) body mass inhibited protein synthesis in liver by 8% and at a higher dose of 10 mg kg(-1) body mass by 38% in the BALB/c mice, when compared to cycloheximide which inhibited protein synthesis by 61%. The effects of FB(1 )on protein synthesis in plant system was studied in germinated maize seedlings exposed to FB(1) at 0.9 microM, 0.009 mM and 0.09 mM concentrations, using (14)C-L: -Leucine as a tracer. Fumonisin B(1) at low, middle, and higher concentrations (0.9 microM, 0.009 mM, and 0.09 mM) inhibited protein synthesis in the seedlings by 4%, 12% and 22%, respectively. The inhibitory effects of FB(1) on the protein synthesis in the animal system in vitro and in vivo conditions, and in the plant system were found to be dose-dependent, though it was less potent compared to cycloheximide.

MeSH terms

  • Animals
  • Cycloheximide / pharmacology
  • Dose-Response Relationship, Drug
  • Fumonisins / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Mycotoxins / pharmacology
  • Protein Biosynthesis / drug effects*
  • Rabbits
  • Reticulocytes / drug effects
  • Reticulocytes / metabolism
  • Zea mays / drug effects
  • Zea mays / metabolism

Substances

  • Fumonisins
  • Mycotoxins
  • fumonisin B1
  • Cycloheximide