Disposition of the toxic protein, bolesatine, in rats: Its resistance to proteolytic enzymes

Abstract

1. Bolesatine is a toxic protein (LD₅₀ oral 3μ3mg/kg in mice) isolated from the mushroom Boletus satanas Lenz, which inhibits protein synthesis in vitro. It induces gastroenteritis in human.

2. ¹⁴C-Bolesatine, given orally to rats (30 μg/kg), is distributed in the gastrointestinal, tract, kidney, liver and, to a lesser extent, in the thymus, spleen and lung. Bolesatine is eliminated in faeces and urine (80% in 24h).

3. The material excreted in urine is not proteolysed, and no protease (trypsin, chymotrypsin, pronase, proteinase K, Staphylococcus aureus (strain V8) protease and pepsin) is found to hydrolyse bolesatine in either its native or denatured form. However, thermolysin hydrolysed denatured bolesatine to a protein having a M_r of about 55 kD.

4. Bolesatine is found in all the following rat liver and kidney subcellular fractions: cytoplasm, mitochondria, ribosomes, microsomes and nuclei.This work was supported in part by grants from Institut National de la Santé et de la Recherche Médicale (INSERM Contrat externe No. 89/2007) and from the Fondation pour la Recherche Médicale. We are grateful to Mr H. Jacquier from the Mycologic Society of Jura for his constant help during the collecting and identification of the mushroom Boletus satanas Lenz, and to Zarmik Moqtaderi for correcting the English.