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Biomedical subjects

S Moreau

Publications and source records attributed to S Moreau.

87 records · Page 5Linked to original sources

Induction of cross-links between DNA and protein by PR toxin, a mycotoxin from Penicillium roqueforti.

PR toxin, a mycotoxin from Penicillium roqueforti, induces DNA--protein cross-links in chromatin of both cultured cells and isolated rat-liver nuclei. The presence of the aldehyde group in the PRT molecule is required for the induction of cross-linking; methylene bridges between nucleic acid and protein are presumably involved in the complex formation. The role of other functional groups of PR toxin is discussed.

Animals↗

Production of Eremofortins A, B, and C Relative to Formation of PR Toxin by Penicillium roqueforti.

The production of various eremophilane-type sesquiterpenes by Penicillium roqueforti strains has allowed us to propose a biochemical pathway for PR toxin synthesis. A time-course study of P. roqueforti metabolite production by high-performance liquid chromatography was performed to check this hypothetical pathway. The results obtained suggested that eremofortin C was the direct precursor of PR toxin in the P. roqueforti cell. Attempts to determine the amount of PR toxin in the mycelium failed. It was shown that the absence of PR toxin in mycelium was due to its instability during the extraction procedure.

Journal Article↗

[In vitro study of glucuronoconjugation of the toxin from Penicillium roqueforti (P.R.T.) and its metabolites].

Rat liver microsome UDP-glucuronyltransferase and labelled UDP-glucuronic acid were incubated either with P.R.T. or the compounds obtained by the in vitro metabolism of the toxin. Under the same conditions, labelled P.R.T. or its labelled metabolites were incubated with UDP glucuronyltransferase. Radioactive metabolites were produced with Eremofortin C and Eremofortin C alcohol and in each case, were identified as the corresponding beta-glucuronide conjugate. No measurable glucuronidation of P.R.T. or P.R.T. alcohol was observed. The results outlined in this paper show a good correlation between the biological effects and the ability of forming a glucuronide conjugate.

Animals↗

Relationships between the chemical structure and the biological properties of some eremophilane compounds related to PR toxin.

The problem of the chemical structure--biological effects relationships has been studied for various eremophilane compounds related to PR toxin (PRT), a mycotoxin synthesized by Penicillium roqueforti. The biological tests were based on in vivo toxicity for male Swiss mice and inhibition of in vitro transcription and tranlation. The results showed a good correlation between the responses obtained for the three tests by the different compounds; thus, the toxic potency and the capacity of inhibiting transcription and translation should be directed by a common chemical structure. The data also indicated that the biological properties are related to the existence of an aldehyde group in position 12. In addition, evidence has been obtained demonstrating the hydrolysis of PRT imine with formation of a PRT-like compound.

Amino Acids↗

[Relationship between chemical structure and biological properties of some fungal metabolites of the eremophilane type].

Certain strains of Penicillium roqueforti and of Phoma exigua var. inoxydabilis synthesize eremophilane-like sesquiterpenes, some of which are biologically active. We have chosen a group of these compounds which are related chemically in order to study the relationships between their chemical structure and their biological properties (toxicity in vivo, capacity of inhibiting RNA and protein syntheses in eucaryotes). This work concerns PR toxin and 2 derived metabolites synthesized by P. roqueforti and phenomenone which is produced by P. exigua. The results allow us to discuss the problem of the active sites of these compounds.

Epoxy Compounds↗

Comparative physiological disposition of some anthraquinone glycosides and aglycones.

The in vitro microbial degradation and the urinary excretion and biliary secretion in rats of two anthraquinone glycosides (sennosides A and B) and four aglycones (sennidins A and B, rhein, and danthron) were studied using a high performance liquid chromatographic system with gradient elution and amperometric detection. Microbial degradation of sennosides A and B occurred almost exclusively in the presence of mice caecum inoculae and was associated with the release of sennidins A and B. Rhein and danthron were indiscriminately metabolized by bacteria sampled from all regions of mice intestine, whereas sennidins lacked stability in biological media. The fraction of the dose administered orally to rats and recovered as aglycones or as glucuronides in bile and urine after 48 hours was five times greater for rhein (15 per cent) and danthron (13.4 per cent) than for sennosides A (1.8 per cent) and B (2.8 per cent) excreted or secreted as sennidins. These results support the concept that anthraquinone glycosides are less likely to enter the systemic circulation and, thus, are able to exert their laxative effect at lower doses than aglycones.

Animals↗

Prophage distribution in coryneform bacteria.

Four temperate bacteriophages of corynebacteria were isolated after UV induction. Phages phi 304L and phi 304S were both induced from Corynebacterium glutamicum ATCC 13058, ATCC 21488, ATCC 21649 and ATCC 21650 strains, and have no known sensitive host. Phages phi 15 and phi 16 were both induced from ATCC 14020 and ATCC 21792. Phage phi 15 formed turbid plaques on Corynebacterium sp. ATCC 21857 and on C. glutamicum ATCC 13058, ATCC 21488, ATCC 21649 and ATCC 21650. Phage phi 16 produced turbid plaques only on C. glutamicum ATCC 21792 cured of prophage phi 16. All these phages belong to the Siphoviridae family. Their genomes consist of a double-stranded DNA with cohesive ends and share no homology with each other. Prophages phi 16, phi 304L and phi 304S were integrated into their respective host chromosomes, whereas prophage phi 15 seemed to persist free in the cell. Cross-hybridizations between phage DNAs and total cellular DNA obtained from 20 strains belonging to the genera Corynebacterium and Brevibacterium did not show the presence of these prophages in strains other than their respective hosts.

Bacteriophages↗

[Interaction of chloroquine with ferriprotophorphyrin IX. Nuclear magnetic resonance study].

Chloroquine is still the antimalarial drug which is the most utilized. Nevertheless the molecular mode of action of this drug is not very well understood. When mouse erythrocytes injected with Plasmodium berghei are exposed to chloroquine, the first biochemical event is rapid accumulation of the drug. This process is energy dependent, saturable and competitively inhibited by drugs of the same therapeutic class (Quinine, Amodiaquine, Mefloquine). Receptors for chloroquine have been proposed for the process of accumulation. The nature of the chloroquine receptor is presently the subject of debates. The latest hypothesis proposed by Chou and coll. [12], is that ferriprotoporphyrin IX, formed by the degradation of hemoglobin by the parasite, binds to chloroquine with a dissociation constant of 3.5.10(-9) M. We studied here the molecular interactions between these two species by Proton Nuclear Magnetic Resonance in order to elucidate the nature and the geometry of were undertaken. The perturbations of the NMR spectra of chloroquine (10(-2) M) induced by addition of hematin or hemin were measured. Two types of measures were undertaken. The first study carried out in organic solvent (DMSO) has shown that the interaction occurred between the acidic functions of hemin and the side-chain nitrogen of chloroquine. The iron atom was not implicated in this process. The second study carried out in aqueous medium (phosphate buffer; 0.1 M; pH = 7) allowed us to demonstrate that chloroquine is able to intercalate into a polymer of hematin. The quinoleic nucleus of chloroquine was intercalated between two dimers of hematin as shown by the broadening of the signal of the quinoleic protons due to very large increase in the correlation time. Finally it was shown that chloroquine is associated as a dimer in aqueous medium by hydrophobic interactions. The association constant is 5.5 M-1.

Animals↗

Generation of free radicals by simple prenylated hydroquinone derivatives, natural antitumor agents from the marine urochordate Aplidium californicum.

The redox properties of simple prenylated hydroquinone derivatives with cytotoxic properties have been studied by absorption and ESR spectroscopies. Both methods evidenced an autoxidation process in which the hydroquinones give rise to a semiquinone radical. Molecular oxygen is the electron acceptor, as demonstrated by spin trapping. No secondary radicals were found in the ESR spectra, either in the presence of hydroxyl anion (alkaline medium) or in the presence of glutathione. Nevertheless, a redox cycle can be initiated by glutathione, giving rise to substantial free-radical production. Thus, although not fully elucidated, the antitumor properties of the three hydroquinones described here can be correlated with their redox properties and their reactivity with thiol-containing peptides such as glutathione.

Animals↗

[Self-healing juvenile cutaneous mucinosis. Clinical, histological and ultrastructural study (author's transl)].

Referring to two other cases reported in the literature, the authors suggest the individualisation of a new form of cutaneous mucinosis which is characterized:--clinically, by the young age of the patient, the peculiar topography of the eruption extending to the face, neck, scalp, abdomen and thighs and the association to deep nodules of the face and the periarticular regions;--biologically by the absence of inflammation, dysglobulinemia, endocrinologic changes or bone marrow plasmocytosis;--by the acute on set of the lesions with spontaneous resolution within a few weeks. The diagnosis is based on histologic and histochemical criteria. The mucinous change occurs in the reticular dermis. Ultrastructural features are similar to those found in other dermal mucinoses. The deposit appears to be composed of an electron lucent matrix containing a micro fibrillar network, probably of polysaccharidic nature. In spite of the histochemical similarity to epithelial mucins, the biochemical composition and mode of production of the deposited substance remain to be elucidated.

Adolescent↗

Induction of antibodies against the Plasmodium falciparum p126 antigen in non-responder H-2b and partial-responder H-2d mice using synthetic peptides.

The p126 Plasmodium falciparum antigen is processed into two fragments, p50 and p73, the latter one containing the subfragments p47 and p18 when the schizonts rupture. An absence of antibody response against the p126 antigen has been reported recently in H-2b mice and limited to the p73 processed fragment in H-2d mice. Synthetic peptides corresponding to various domains of the molecule have been used to immunize mice in order to overcome the absence of an immune response. Synthetic peptides corresponding to the N-terminus of p50 or p18 as well as to the C-terminus of p47 were unable to induce anti-peptide antibodies when injected carrier-free or coupled to ovalbumin. Synthetic peptides corresponding to the C-terminus of p18 or composed of 6 or 9 serines were able to induce anti-peptide antibodies when injected coupled to a carrier protein. However, none of these antibodies was able to recognize the native p126 molecule. Various synthetic peptides corresponding to the 6-octapeptide [Nt47 (6 x 8)] or the 4-octapeptide [Nt47(4 x 8)] repeat sequence localized at the N-terminus of the p47 have also been used to immunize mice. No antibodies were generated using a carrier-free [Nt47(6 x 8)-Cys]2 or [Nt47 (4 x 8)-Cys]2 peptide, an octameric multiple antigen peptide construct [Nt47(6 x 8)]-MAP or the [Nt47(6 x 8)] coupled to one or two palmitic acids. In contrast, [Nt47(6 x 8)]-Cys coupled to either tetanus toxoid (TT) or ovalbumin (OVA) and [Nt47(4 x 8)]-Cys coupled to OVA induced antibodies against the synthetic peptide and the native p126 molecule in both H-2d and H-2b mice. A multiple antigen peptide construct [Nt47(4 x 8)-MSP-3b]-MAP containing 4 [Nt47(4 x 8)] and 4 [MSP-3b] also induced antibodies against the synthetic peptide [Nt47(4 x 8)-Cys]2 and the native p126 molecule in both H-2d and H-2b mice.

Amino Acid Sequence↗