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Protein synthesis inhibition in rat liver by the mycotoxin patulin
Abstract:
Patulin, a carcinogenic mycotoxin, inhibits in vivo and in vitro protein synthesis in rat liver. The in vivo inhibition culminates 5 h after toxin administration and reaches a maximum of 65% with regard to control values; a breakdown of polysomes is associated with the translational blockage. However in in vitro systems, the cellular fractions obtained from patulin-treated rats appear equally as active in protein synthesizing ability and as sensitive to the toxin action as those prepared from control animals. The in vitro inhibition by patulin is dose related. The postmitochondrial system is less sensitive than that functioning with isolated polysomes and pH 5 enzyme. This difference might be due to the presence of soluble factor(s) that counteract patulin action. We propose that the inhibition of protein synthesis by patulin may result from an interaction of the drug with active SH groups at the membrane level (amino acid transport, ion equilibrium) and/or at the cytoplasmic level (enzymes and factors involved in the translational process).
Insights
Patulin, a carcinogenic mycotoxin, significantly inhibits protein synthesis in rat liver both in vivo and in vitro. This toxin disrupts polysomes, suggesting a potential interaction with cellular sulfhydryl groups.
Area of Science:
- Toxicology
- Molecular Biology
- Biochemistry
Background:
- Patulin is a carcinogenic mycotoxin with known adverse health effects.
- Protein synthesis is a fundamental cellular process crucial for cell function and survival.
Purpose of the Study:
- To investigate the effects of patulin on protein synthesis in rat liver.
- To elucidate the mechanisms underlying patulin-induced inhibition of protein synthesis.
Main Methods:
- In vivo administration of patulin to rats followed by analysis of liver protein synthesis.
- In vitro studies using isolated cellular fractions (polysomes, pH 5 enzyme, postmitochondrial system) to assess direct effects of patulin.
- Dose-response analysis of patulin's inhibitory effects.
Main Results:
- Patulin caused a significant inhibition of in vivo protein synthesis, peaking at 65% inhibition 5 hours post-administration.
- A breakdown of polysomes was observed in vivo, correlating with translational blockage.
- In vitro, cellular fractions from patulin-treated rats showed similar protein synthesis activity and sensitivity to the toxin as controls.
- In vitro inhibition was dose-dependent, with isolated polysomes and pH 5 enzyme being more sensitive than the postmitochondrial system.
Conclusions:
- Patulin inhibits protein synthesis in rat liver through disruption of translation.
- The reduced sensitivity in the postmitochondrial system suggests the presence of soluble factors that may counteract patulin's effects.
- Patulin's mechanism likely involves interaction with active sulfhydryl (SH) groups at the membrane or cytoplasmic level, affecting amino acid transport, ion equilibrium, or translational factors.