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Protein synthesis in rat brain following neonatal exposure to lead
Insights
Lead exposure in young rats significantly impairs brain protein synthesis by reducing aminoacyl-tRNA synthetase activity. Ribosomal peptide formation and initiation factor binding were also affected.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Lead exposure is a significant public health concern, particularly for developing brains.
- Understanding the molecular mechanisms of lead neurotoxicity is crucial for developing effective interventions.
Purpose of the Study:
- To investigate the impact of developmental lead exposure on protein synthesis in rat brains.
- To identify specific molecular targets within the protein synthesis pathway affected by lead.
Main Methods:
- Suckling and weanling rats were exposed to lead via maternal diet and direct injection.
- Brain homogenates were fractionated into postmitochondrial supernatant, ribosomes, and initiation factors.
- In vitro assays measured protein synthesizing activity, peptide formation, aminoacyl-tRNA synthetase activity, and tRNA-ribosome binding.
Main Results:
- Lead-exposed rat brain homogenates showed significantly reduced protein synthesizing activity.
- Peptide formation by brain ribosomes remained unchanged.
- Aminoacyl-tRNA synthetase activity was significantly reduced, explaining the overall decrease in peptide formation.
- Methionyl-tRNAfMet binding to ribosomes increased with initiation factors from lead-exposed rats.
Conclusions:
- Developmental lead exposure disrupts brain protein synthesis primarily by inhibiting aminoacyl-tRNA synthetase.
- While ribosomal peptide formation is unaffected, the initiation step may be altered, suggesting complex neurotoxic effects.
Abstract:
(1) Suckling rats were exposed to lead through the milk of their dams who received a diet of 4% lead carbonate and weanling rats were exposed to 2 injections of 5.0 mg Pb2+/100 g body weight. The brains were used to prepare the following homogenate fractions: postmitochondrial supernatant, postmicrosomal supernatant, ribosomes, initiation factors. (2) The postmitochondrial supernatant fractions were tested in vitro for protein synthesizing activity using the incorporation of labelled phenylalanine, and phenylalanyl-tRNA into peptide. The preparations from the lead-exposed rats had a significant reduction in activity. (3) Peptide formation with the brain ribosomes was not changed in the lead-exposed rats. (4) The aminoacyl-tRNA synthetase reaction was significantly reduced and accounted for most of the reduced peptide formation with brain homogenates from lead-exposed rats. (5) The binding of methionyl-tRNAfMet to ribosomes was increased using initiation factor preparations from the brain of lead-exposed rats.