Integration of proteomic and metabolomic analyses: New insights for mapping informal workers exposed to potentially toxic elements

Author(s)

Miranda Araujo, Alda Neis ; Nogueira Leroux, Isabelle ; Sousa Furtado, Danielle Zildeana ; da Silva Ferreira, Ana Paula Sacone ; Batista, Bruno Lemos ; Torres Silva, Heron Dominguez ; Handakas, Evangelos ; Assuncao, Nilson Antonio ; Kaneshiro Olympio, Kelly Polido

• Document type: Journal article
• Source: FRONTIERS IN PUBLIC HEALTH; v. 10, p. 11-pg., 2023-01-25.

Abstract

Occupational exposure to potentially toxic elements (PTEs) is a concerning reality of informal workers engaged in the jewelry production chain that can lead to adverse health e ects. In this study, untargeted proteomic andmetabolomic analyses were employed to assess the impact of these exposures on informal workers' exposome in Limeira city, Sao Paulo state, Brazil. PTE levels (Cr, Mn, Ni, Cu, Zn, As, Cd, Sn, Sb, Hg, and Pb) were determined in blood, proteomic analyses were performed for saliva samples (n = 26), and metabolomic analyses in plasma (n = 145) using ultra-high performance liquid chromatography (UHPLC) coupled with quadrupole-time-of-flight (Q-TOF) mass spectrometry. Blood PTE levels of workers, controls, and their family members were determined by inductively coupled plasma-mass spectrometry (ICP-MS). High concentration levels of Sn and Cu were detected in welders' blood (p < 0.001). Statistical analyses were performed using MetaboAnalyst 4.0. The results showed that 26 proteins were upregulated, and 14 proteins downregulated on the welder group, and thirty of these proteins were also correlated with blood Pb, Cu, Sb, and Sn blood levels in the welder group (p < 0.05). Using gene ontology analysis of these 40 proteins revealed the biological processes related to the upregulated proteins were translational initiation, SRP-dependent co-translational protein targeting to membrane, and viral transcription. A Metabolome-Wide Association Study (MWAS) was performed to search for associations between blood metabolites and exposure groups. A pathway enrichment analysis of significant features from the MWAS was then conducted with Mummichog. A total of 73 metabolomic compounds and 40 proteins up or down-regulated in welders were used to perform a multi-omics analysis, disclosing seven metabolic pathways potentially disturbed by the informal work: valine leucine and isoleucine biosynthesis, valine leucine and isoleucine degradation, arginine and proline metabolism, ABC transporters, central carbon metabolism in cancer, arachidonic acid metabolism and cysteine and methionine metabolism. The majority of the proteins found to be statistically up or downregulated in welders also correlated with at least one blood PTE level, providing insights into the biological responses to PTE exposures in the informal work exposure scenario. These findings shed new light on the e ects of occupational activity on workers' exposome, underscoring the harmful e ects of PTE. (AU)

• FAPESP's process: 18/18391-0 - The "omics" era applied to society: the impact of formal and informal labor on the exposome of workers with an emphasis on metabolomics, transcriptomics and lipidomics
• Grantee: Kelly Polido Kaneshiro Olympio
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/11087-8 - From exposome up to Regulatory Toxicology: a thematic study on potentially toxic elements (PTEs) exposure of families inserted in informal productive arrangement in the jewelry and fashion jewelry chain from Limeira, SP
• Grantee: Kelly Polido Kaneshiro Olympio
• Support Opportunities: Regular Research Grants