The immunotoxin‐enhancing properties of monensin and of human‐serum‐albumin—monensin conjugates are severely impaired in the presence of human serum. In this study we have therefore investigated the ...interaction between serum proteins and monensin leading to the inactivation of monensin function as immunotoxin potentiator. We found that the binding of monensin‐specific mAb to thioether‐cross‐linked or disulfide‐cross‐linked protein‐monensin conjugates is negatively affected by serum, as indicated by immunoenzymic (ELISA) and radioimmunobinding analysis. Size‐exclusion chromatography of serum samples indicated that the greatest blocking effect is due to protein components of 40–90 kDa eluting as a broad peak (peak 4). Analysis of the proteins contained within peak 4 by ion‐exchange chromatography followed by microsequencing revealed that the major components of peak no. 4 were transferrin, human serum albumin and immunoglobulin fragments. Investigations on the nature of the interactions between serum proteins and monensin leading to monensin inactivation were conducted by affinity chromatography of serum on immobilized human‐serum‐albumin—monensin conjugates, size‐exclusion chromatography, SDS/PAGE analysis of serum‐treated human‐serum‐albumin—monensin conjugates, and evaluation of the stability of immobilized human‐serum‐albumin‐bound 125I‐monensin following treatment with serum. Addition of esterase inhibitors (e.g. EDTA, 4‐nitrophenyl phosphate) or prior treatment of the serum at 56°C partially reversed the serum effects observed. We conclude that serum proteins block the immunotoxin‐enhancing effect of monensin and of human‐serum‐albumin—monensin conjugates by multiple mechanisms involving hydrophobic and covalent interactions and enzyme‐mediated cleavage of protein‐bound monensin.
Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the
neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral ...nervous systems. The
enzyme inactivation, induced by various inhibitors, leads to acetylcholine accumulation, hyperstimulation of nicotinic and
muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the
enzyme as their primary target, are applied as relevant drugs and toxins. This review presents an overview of toxicology
and pharmacology of reversible and irreversible acetylcholinesterase inactivating compounds. In the case of reversible
inhibitors being commonly applied in neurodegenerative disorders treatment, special attention is paid to currently
approved drugs (donepezil, rivastigmine and galantamine) in the pharmacotherapy of Alzheimer’s disease, and toxic
carbamates used as pesticides. Subsequently, mechanism of irreversible acetylcholinesterase inhibition induced by
organophosphorus compounds (insecticides and nerve agents), and their specific and nonspecific toxic effects are
described, as well as irreversible inhibitors having pharmacological implementation. In addition, the pharmacological
treatment of intoxication caused by organophosphates is presented, with emphasis on oxime reactivators of the inhibited
enzyme activity administering as causal drugs after the poisoning. Besides, organophosphorus and carbamate insecticides
can be detoxified in mammals through enzymatic hydrolysis before they reach targets in the nervous system.
Carboxylesterases most effectively decompose carbamates, whereas the most successful route of organophosphates
detoxification is their degradation by corresponding phosphotriesterases.
Degradation experiments on synthesized sulphanilic acid and 5 carbon-14-labelled azo dyes, using a charcoal-containing polyurethane sponge or 2-methoxyethanol to trap volatile organic compounds, ...showed that the lignin-degrading white-rot fungus Phanerochaete chrysosporium mineralized all sulphonated azo dyes, and the substitution pattern had little influence on degradative ability. The lignocellulolytic soil actinomycete Streptomyces chromofuscus mineralized dyes with the lignin-like guaiacol structure attached to the sulphonated aromatic ring but failed to mineralize aromatics with sulpho groups and both sulpho and azo groups. Potential applications of the 2 test micro-organisms for the biodegradation of resistant xenobiotic compounds required further investigation. There are 59 references. (see also following abstract).
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