ABSTRACT
The neurotoxicity of aluminium (Al) involves bundling of neurofilaments, increased chromatin binding and decreased protein synthesis in Al injected rabbits. Thus, using an amphipathic Al ligand, maltol, experiments were carried out to examine whether or not administration of Al to lactating mother rabbits reduces brain protein synthesis in their offspring. Lactating mother rabbits received s.c. injections 3 times weekly of aluminium (Al) maltolate (1 mg Al/kg body wt) or an equivalent weight of maltol, for 4 weeks post-partum. Polysome preparations were obtained from the brain of their infants in order to assess mRNA translation in cell-free protein synthesizing systems. The brain polysomes showed a statistically significant reduction in the incorporation of [14C]leucine into protein. The poly (A)+ and poly (A)- fractions obtained from these polysomes showed reductions of 44% or more in the incorporation of [35S]methionine into protein. A variety of products separated by SDS-polyacrylamide gel electrophoresis all exhibited decreased labelling. These experiments suggest that infant rabbits exposed to a highly neurotoxic form of Al in milk exhibit changes in brain protein synthesis which resemble those in infants injected directly with Al.
Subject(s)
Aluminum Compounds/toxicity , Animals, Newborn/metabolism , Brain/drug effects , Maternal Exposure , RNA, Messenger/metabolism , Aluminum Compounds/metabolism , Animals , Body Weight , Brain/metabolism , Female , Lactation , Leucine/metabolism , Organ Size , Pyrones/metabolism , RabbitsABSTRACT
1. Infant rabbits received s.c.injections 3 times weekly of low doses of aluminium (A1) maltolate (0.5-1.5 mg Al/kg body wt) or aluminium lactate (8 mg Al/kg body wt) from 5 or 10 days of age to 14 or 22 days of age. 2. Brain was used to provide a cell-free protein synthesizing system and this system exhibited increased activity in preparations from Al-exposed infants. The mRNA fraction obtained from the brain polysomal RNA also was more active following Al exposure. 3. The synthesis of immunoprecipitable calmodulin was significantly elevated.
Subject(s)
Aluminum/pharmacology , Animals, Newborn , Brain/metabolism , Nerve Tissue Proteins/biosynthesis , Aluminum/administration & dosage , Animals , Brain/drug effects , Calmodulin/biosynthesis , Cell-Free System , Lactates/pharmacology , Lactic Acid , Organometallic Compounds/pharmacology , Polyribosomes/metabolism , Pyrones/pharmacology , RNA, Messenger/metabolism , RabbitsABSTRACT
1. Polysomes were isolated from the brain of infant rabbits at 22 days of age. The animals received s.c. injections 3 times weekly of aluminium (Al) maltolate (3 mg Al/kg body wt) or Al lactate (16 mg Al/kg body wt) from 5 days of age. 2. The polysomes were used to direct the incorporation of [14C]leucine into peptides in a brain protein synthesizing system and exhibited a decreased activity when obtained from aluminum exposed infants. 3. The mRNA obtained from the polysomes was used to direct the incorporation of [35S]methionine into peptides in an mRNA dependent rabbit reticulocyte lysate. The translatability of the mRNA derived from aluminum exposed infant brains was significantly lower than that of preparations from control infant rabbits. 4. Al bound to maltolate, a ligand soluble in lipids as well as water, was considerably more detrimental to brain protein synthesis than Al bound to lactate.
