A proteomic study to unveil lead toxicity-induced memory impairments invoked by synaptic dysregulation.

Autor:	Mohanraj N; Department of Biophysics, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India., Joshi NS; Institute of Bioinformatics, Bengaluru, India.; Manipal Academy of Higher Education, Manipal, India., Poulose R; Department of Biophysics, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India., Patil RR; Department of Biophysics, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India., Santhoshkumar R; Electron Microscopy-Common Research Facility, Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India., Kumar A; Department of Biophysics, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India., Waghmare GP; Department of Biophysics, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India., Saha AK; Department of Biophysics, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India., Haider SZ; Department of Biophysics, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India., Markandeya YS; Department of Biophysics, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India., Dey G; Institute of Bioinformatics, Bengaluru, India., Rao LT; Department of Neurophysiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India., Govindaraj P; Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India., Mehta B; Department of Biophysics, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India.
Jazyk:	angličtina
Zdroj:	Toxicology reports [Toxicol Rep] 2022 Jul 07; Vol. 9, pp. 1501-1513. Date of Electronic Publication: 2022 Jul 07 (Print Publication: 2022).
DOI:	10.1016/j.toxrep.2022.07.002
Abstrakt:	Lead (Pb 2+ ), a ubiquitously present heavy metal toxin, has various detrimental effects on memory and cognition. However, the molecular processes affected by Pb 2+ 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 Pb 2+ exposure induced impairments in spatial cognition. Further, proteomic analysis of synaptosomal fractions revealed differential alteration of 289 proteins, which shows functional significance in elucidating Pb 2+ induced physiological changes. Focusing on the association of Small Ubiquitin-like MOdifier (SUMO), a post-translational modification, with Pb 2+ 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 Pb 2+ induced physiological imbalance. These findings identify SUMOylation as a vital protein modifier with potential roles in hippocampal memory consolidation and regulation of cognition. Data Availbility: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD034212". Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2022 The Authors.)
Databáze:	MEDLINE
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