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pmid:36518382
A proteomic study to unveil lead toxicity-induced memory impairments invoked by synaptic dysregulation.
Nivedha Mohanraj · Neha S Joshi · Roshni Poulose · Rahul R Patil · Rashmi Santhoshkumar · Anubhav Kumar · Girish P Waghmare · Amit Kumar Saha · Syeda Zehra Haider · Yogananda S Markandeya · Gourav Dey · Laxmi T Rao · Periyasamy Govindaraj · Bhupesh Mehta
Toxicology reports · 2022 doi:10.1016/j.toxrep.2022.07.002
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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However, the molecular processes affected by Pb2+ causing structural and functional anomalies are still unclear. To explore this, we employed behavioral and proteomic approaches using rat pups exposed to lead acetate through maternal lactation from postnatal day 0 (P0) until weaning. Behavioral results from three-month-old rats clearly emphasized the early life Pb2+ exposure induced impairments in spatial cognition. Further, proteomic analysis of synaptosomal fractions revealed differential alteration of 289 proteins, which shows functional significance in elucidating Pb2+ induced physiological changes. Focusing on the association of Small Ubiquitin-like MOdifier (SUMO), a post-translational modification, with Pb2+ induced cognitive abnormalities, we identified 45 key SUMO target proteins. The significant downregulation of SUMO target proteins such as metabotropic glutamate receptor 3 (GRM3), glutamate receptor isoforms 2 and 3 (GRIA 2 and GRIA3) and flotilin-1 (FLOT1) indicates SUMOylation at the synapses could contribute to and drive Pb2+ induced physiological imbalance. These findings identify SUMOylation as a vital protein modifier with potential roles in hippocampal memory consolidation and regulation of cognition.\nData availbility: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD034212".", "claims": [{"id": "claim-method", "statement": "For behavioural data, statistical analysis was performed by two-way ANOVA using Origin Pro software. Statistical analysis for the quantified proteins was carried out using the Perseus software platform. 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