Dataset Information

Proteomic analysis of human neuronal SH-SY5Y in neurological diseases exposed to phtalates and metaks

ABSTRACT: This study aimed to reveal biological pathways involved in neurodevelopmental disorders after co-exposure to phthalates and metals by using a multi-omics analysis in a human neuronal cell line, SH-SY5Y. Mixtures of phthalates (DEHP, DiNP, BBzP) and metals (lead, methylmercury, total mercury, cadmium) were selected as they were the most abundant ones in the REPRO_PL and PHIME cohorts, respectively, in the frame of the EU project HEALS, investigating if exposure to those pollutants could be associated to neurodevelopmental disorders in children across Europe. Their concentrations in the human brain were calculated at the INTEGRA computational platform. The differentiated cell line was exposed to this mixture and a ten-times higher one for 4 days. Transcriptomic and proteomic analyses were performed and the data analyzed using advanced bioinformatics tools. Co-exposure to phthalates and metals leads to the perturbation of various metabolic pathways associated with neuronal diseases. The proteomic data showed that a number of neurological diseases are statistically associated with the exposure of the SH-SY5Y cells to the mixtures of pollutants. In conclusion, this study reveals that co-exposure to phthalates and metals disturbs biochemical processes in the brain model, which could be associated with clinical neurodevelopmental perturbations in cohorts.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Chiara guerrera

LAB HEAD: Chiara Guerrera

PROVIDER: PXD033091 | Pride | 2023-12-20

REPOSITORIES: Pride

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Publications

Aggressiveness and Metastatic Potential of Breast Cancer Cells Co-Cultured with Preadipocytes and Exposed to an Environmental Pollutant Dioxin: An <i>in Vitro</i> and <i>in Vivo</i> Zebrafish Study.

Koual Meriem M Tomkiewicz Céline C Guerrera Ida Chiara IC Sherr David D Barouki Robert R Coumoul Xavier X

Environmental health perspectives 20210308 3

<h4>Background</h4>Breast cancer (BC) is a major public health concern, and its prognosis is very poor once metastasis occurs. The tumor microenvironment and chemical pollution have been suggested recently to contribute, independently, to the development of metastatic cells. The BC microenvironment consists, in part, of adipocytes and preadipocytes in which persistent organic pollutants (POPs) can be stored.<h4>Objectives</h4>We aimed to test the hypothesis that these two factors (2,3,7,8-tetrac ...[more]

PMID: 33683140

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Project description:Micronutrient deficiencies and environmental exposures have been to known to adversely impact brain and nervous system functions in adults and children worldwide. However, few studies have examined the short and long-term impact of these risk factors on neurodevelopmental outcomes in children in low-income countries, where the effects are likely to be more pronounced due to limited resources for monitoring and insufficient regulations. Biological risk factors of relevance include micronutrient deficiencies such as zinc and exposure to heavy metals such as lead and mercury. Studies have suggested an association between neurodevelopmental impairment and micronutrient deficiency as well as exposure to a number of heavy metals and environmental toxins. Moreover, findings also suggest that risk factors for adverse developmental outcomes that are independently significant may have the potential for causing cumulative increases in adverse effects. In Sub-Saharan Africa, severe malaria is a leading risk factor for long-term neurocognitive impairment in children. Zinc deficiency or exposure to heavy metals could influence risk of severe malaria, modify the risk of neurocognitive impairment in children with severe malaria, or independently affect risk of neurocognitive impairment. Untargeted analyses for potential environmental exposures or metabolomic changes in children with cerebral malaria vs. without cognitive impairment or in children with higher vs. lower cognitive scores, could also identify new risk factors for neurodevelopmental impairment in Ugandan children with cerebral malaria.In our completed study in Kampala, we assessed neurologic and developmental impairment in children with cerebral malaria [CM] or severe malarial anemia [SMA], as compared to health community children from the same extended household as the children with CM or SMA. As an extension of this study, we are interested in determining levels of micronutrients such as zinc in the population, and in addition, determining exposure levels of heavy metals (lead, mercury, copper, manganese etc.) in samples collected from children with severe malaria and community controls. The primary hypotheses of this study is that nutrient deficiencies or exposure to heavy metals influence short and long term neurocognitive outcomes in healthy community children and in children with severe malaria, and that children with cerebral malaria have specific metabolomic changes that relate to long-term neurocognitive impairment. The specific aims of our study are:Aim 1: To determine levels of zinc, heavy metals, and biomarkers associated with inflammation in children presenting with different forms of severe malaria (SM) and in healthy community children (CC). The working hypothesis of this aim is that 1) children with SM will have lower zinc levels compared to CC; 2) children with SM will present with higher toxic metal exposure and higher levels of biomarkers associated with inflammation than CC.Aim 2: To investigate how micronutrient deficiency, toxic metal exposure and inflammatory biomarkers affect short and long term neurodevelopmental outcomes and growth in children with severe malaria and community children (CC).The working hypothesis of this aim is that the lower levels of zinc, and presence of toxic metals in high concentrations will independently contribute to worsening neurodevelopmental outcomes and worsening growth over time in children with severe malaria and in community children. An alternate hypothesis is that micronutrient deficiency, toxic metal exposure and inflammatory states may interact with each other and with severe malaria to produce greater neurodevelopmental impairment, i.e., that the contribution is not independent but interactive.Aim 3: To determine whether the CSF metabolome differs according to level of neurodevelopmental impairment in children with cerebral malaria. The working hypothesis of this aim is that neurodevelopmental impairment in children with cerebral malaria is associated with changes in the CSF metabolome.

Project description:Focal and segmental glomerulosclerosis (FSGS) is a severe form of idiopathic nephrotic syn-drome (INS), a glomerulopathy of presumable immune origin and attributed to extrarenal path-ogenic circulating factors. FSGS recurrence (rFSGS) after transplant occurs in 30 to 50% of cases. Direct analysis of patient plasma proteome has been scarcely addressed to date, mainly due to methodological difficulties associated with plasma complexity and dynamic range. In this study, firstly we compared different methods of plasma preparation, secondly we compared the plasma proteome of rFSGS and controls using two preparation methods, and thirdly we analyzed the early proximal signaling events in podocytes subjected to patient plasma, by a combination of phosphoproteomics and lipid raft proteomics (raftomics). By combining immunodepletion and high pH fractionation, we performed a differential proteomic analysis of soluble plasma pro-teins and of extracellular vesicles (EV) obtained from healthy controls, non-INS patient controls, and rFSGS patients (n=4). In both soluble and EV protein sets from rFSGS patients we found a statistically significant increase in a cluster of proteins involved in neutrophil degranulation. A group of lipid binding proteins, generally associated with lipoproteins, was found decreased in the soluble set from rFSGS patients. In addition, three aminoacid transporters involved in mTORC1 activation were found significantly increased in EV from rFSGS. Next, we incubated human podocytes for 30min with 10% plasma from both groups of patients. Phosphoproteomics and raftomics of podocytes revealed profound differences in proteins involved in the mTOR pathway, in autophagy, and in cytoskeleton organization. We analyzed the correlation between the abundance of plasma and plasma-regulated podocyte proteins. The observed changes high-light some of the mechanisms involved in FSGS recurrence and could be used as specific early markers of circulating factor activity on podocytes.

Dataset Information

Proteomic analysis of human neuronal SH-SY5Y in neurological diseases exposed to phtalates and metaks

Publications

Aggressiveness and Metastatic Potential of Breast Cancer Cells Co-Cultured with Preadipocytes and Exposed to an Environmental Pollutant Dioxin: An <i>in Vitro</i> and <i>in Vivo</i> Zebrafish Study.

Similar Datasets

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