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Is Cadmium Toxicity Tissue-Specific? Toxicogenomics Studies Reveal Common and Specific Pathways in Pulmonary, Hepatic, and Neuronal Cell Models

Title: Is Cadmium Toxicity Tissue-Specific? Toxicogenomics Studies Reveal Common and Specific Pathways in Pulmonary, Hepatic, and Neuronal Cell Models
Authors: Matilde Forcella; Pierre Lau; Marco Fabbri; Paola Fusi; Monica Oldani; Pasquale Melchioretto; Laura Gribaldo; Chiara Urani
Source: International Journal of Molecular Sciences, Vol 23, Iss 1768, p 1768 (2022)
Publisher Information: MDPI AG
Publication Year: 2022
Collection: Directory of Open Access Journals: DOAJ Articles
Subject Terms: cadmium; cancer; metal homeostasis; neurotoxicity; toxicogenomics; Biology (General); QH301-705.5; Chemistry; QD1-999
Description: Several harmful modifications in different tissues-organs, leading to relevant diseases (e.g., liver and lung diseases, neurodegeneration) are reported after exposure to cadmium (Cd), a wide environmental contaminant. This arises the question whether any common molecular signatures and/or Cd-induced modifications might represent the building block in initiating or contributing to address the cells towards different pathological conditions. To unravel possible mechanisms of Cd tissue-specificity, we have analyzed transcriptomics data from cell models representative of three major Cd targets: pulmonary (A549), hepatic (HepG2), and neuronal (SH-SY-5Y) cells. Further, we compared common features to identify any non-specific molecular signatures. The functional analysis of dysregulated genes (gene ontology and KEGG) shows GO terms related to metabolic processes significantly enriched only in HepG2 cells. GO terms in common in the three cell models are related to metal ions stress response and detoxification processes. Results from KEGG analysis show that only one specific pathway is dysregulated in a significant way in all cell models: the mineral absorption pathway. Our data clearly indicate how the molecular mimicry of Cd and its ability to cause a general metal ions dyshomeostasis represent the initial common feature leading to different molecular signatures and alterations, possibly responsible for different pathological conditions.
Document Type: article in journal/newspaper
Language: English
Relation: https://www.mdpi.com/1422-0067/23/3/1768; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067; https://doaj.org/article/38c2897616c04f288b1800e93d6913b6
DOI: 10.3390/ijms23031768
Availability: https://doi.org/10.3390/ijms23031768; https://doaj.org/article/38c2897616c04f288b1800e93d6913b6
Accession Number: edsbas.6C584B
Database: BASE