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

Mohanraj, Nivedha; Joshi, Neha S.; Poulose, Roshni; Patil, Rahul R.; Santhoshkumar, Rashmi; Kumar, Anubhav; Waghmare, Girish P.; Saha, Amit Kumar; Haider, Syeda Zehra; Markandeya, Yogananda S.; Dey, Gourav; Rao, Laxmi T.; Govindaraj, Periyasamy; Mehta, Bhupesh

doi:10.1016/j.toxrep.2022.07.002

Cited by 3 publications

(4 citation statements)

References 81 publications

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“…The sumoylation of FLOT1 can trigger its nuclear heterotopic, which is related to the occurrence of prostate cancer (PCa) ( 5 ). In addition, one study has shown that the sumoylation of FLOT1 participates in modulating synaptic plasticity ( 25 ) ( Table I ).…”

Section: Ptms Of Flot1mentioning

confidence: 99%

“…Intact lipid rafts are necessary to maintain synaptic stability ( 18 ). The lipid raft-associated protein FLOT1 is directly related to synaptic plasticity ( 25 ). It plays an important role in promoting hippocampal neuronal differentiation and neurite growth in the early stages of neuronal development.…”

Section: Physiological Effects Of Flot1mentioning

confidence: 99%

“…Abnormal regulation of these can lead to the occurrence of nervous system diseases, such as PD ( 16 , 30 ). In addition, FLOT1 can promote the formation of hippocampal synapses, increase the number of glutamatergic synapses, and trigger axonal growth through the recruitment of N-cadherin ( 2 , 25 , 33 ). Finally, FLOT1 plays a role in T-cell activation ( 38 ), regulating cell proliferation ( 35 ), and participating in cell adhesion ( 38 ), amongst other processes.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

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The roles of FLOT1 in human diseases (Review)

Zhan,

Ye,

Jin

2023

Mol Med Rep

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FLOT1, a scaffold protein of lipid rafts, is involved in several biological processes, including lipid raft protein-dependent or clathrin-independent endocytosis, and the formation of hippocampal synapses, amongst others. Increasing evidence has shown that FLOT1 can function as both a cancer promoter and cancer suppressor dependent on the type of cancer. FLOT1 can affect the occurrence and development of several types of cancer by affecting epithelial-mesenchymal transition, proliferation of cancer cells, and relevant signaling pathways, and is regulated by long intergenic non-coding RNAs or microRNAs. In the nervous system, overexpression or abnormally low expression of FLOT1

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Section: Ptms Of Flot1mentioning

confidence: 99%

Section: Physiological Effects Of Flot1mentioning

confidence: 99%

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

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The roles of FLOT1 in human diseases (Review)

Zhan,

Ye,

Jin

2023

Mol Med Rep

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“…Exposure to arsenic from food and water leads to cancer, skin lesions, cardiovascular disease, and diabetes [29][30][31][32]. Lead reduces brain development, causes anemia, body weakness, kidney, and brain damage [33][34][35]. Uranium can cause lung cancer, liver and kidney damage [36,37].…”

Section: Introductionmentioning

confidence: 99%

Toxic Heavy Metals in Soil and Plants from a Gold Mining Area, South Africa

Raji¹,

Palamuleni²

2023

Heavy Metals - Recent Advances

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The mining of mineral deposits abundant in South Africa has led to the release of toxic heavy metals into the environment. The aim of this study was to investigate heavy metal pollution from a gold mining area. The concentrations of arsenic, cadmium, lead, and zinc were analyzed in soil and plants found within 500 m and 1000 m radius of a gold mine established in North-West. The concentrations of these heavy metals were determined using Inductively Coupled Plasma Mass Spectrometry. The results showed that the concentrations of the studied heavy metals were all below the national and international threshold but higher than the concentrations found several kilometers away from the mining area, the natural background concentration. The results from the pollution load index shows that the topsoil is contaminated for the selected heavy metals. There was accumulation of the studied heavy metals in the studied Eragrostis hypnoides plant’s leaves and roots. In this study, it was revealed that zinc and cadmium bioaccumulated in the plant via the soil. These findings suggests that the consumption of agricultural products from farms within the 1 km radius of the mining site could be detrimental to the wellbeing of direct and indirect consumers.

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Unraveling the molecular landscape of lead-induced cochlear synaptopathy: a quantitative proteomics analysis

Bhatia,

Mehmood,

Doyon-Reale

et al. 2024

Front. Cell. Neurosci.

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IntroductionExposure to heavy metal lead can cause serious health effects such as developmental neurotoxicity in infants, cognitive impairment in children, and cardiovascular and nephrotoxic effects in adults. Hearing loss is one of the toxic effects induced by exposure to lead. Previous studies demonstrated that exposure to lead causes oxidative stress in the cochlea and disrupts ribbon synapses in the inner hair cells.MethodsThis study investigated the underlying mechanism by evaluating the changes in the abundance of cochlear synaptosomal proteins that accompany lead-induced cochlear synaptopathy and hearing loss in mice. Young-adult CBA/J mice were given lead acetate in drinking water for 28 days.ResultsLead exposure significantly increased the hearing thresholds, particularly at the higher frequencies in both male and female mice, but it did not affect the activity of outer hair cells or induce hair cell loss. However, lead exposure decreased wave-I amplitude, suggesting lead-induced cochlear synaptopathy. In agreement, colocalization of pre- and post-synaptic markers indicated that lead exposure decreased the number of paired synapses in the basal turn of the cochlea. Proteomics analysis indicated that lead exposure increased the abundance of 352 synaptic proteins and decreased the abundance of 394 synaptic proteins in the cochlea. Bioinformatics analysis indicated that proteins that change in abundance are highly enriched in the synaptic vesicle cycle pathway.DiscussionTogether, these results suggest that outer hair cells are not the primary target in lead-induced ototoxicity, that lead-induced cochlear synaptopathy is more pronounced in the basal turn of the cochlea, and that synaptic vesicle cycle signaling potentially plays a critical role in lead-induced cochlear synaptopathy.

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

Cited by 3 publications

References 81 publications

The roles of FLOT1 in human diseases (Review)

The roles of FLOT1 in human diseases (Review)

Toxic Heavy Metals in Soil and Plants from a Gold Mining Area, South Africa

Unraveling the molecular landscape of lead-induced cochlear synaptopathy: a quantitative proteomics analysis

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