| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Toxicology Reports, Vol 9, Iss , Pp 1501-1513 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2214-7500 |
| DOI: |
10.1016/j.toxrep.2022.07.002 |
| Popis: |
Lead (Pb2+), a ubiquitously present heavy metal toxin, has various detrimental effects on memory and cognition. 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. Data availbility: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD034212". |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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