Toxicoproteomics of Mono(2-ethylhexyl) phthalate and Perfluorooctanesulfonic Acid in Models of Prostatic Diseases.

Benign and malignant prostatic diseases are common, costly, and burdensome; moreover, they share fundamental underlying molecular processes. Several ubiquitous contaminants may perturb these processes, possibly via peroxisome proliferator-activated receptor (PPAR) signaling, but the role of environmental exposures─particularly mixtures─in prostatic diseases is undefined. In the present study, nontumorigenic prostate stromal cells and metastatic prostate epithelial cells were exposed to ubiquitous exogenous PPAR ligands under different dosing paradigms, including a mixture, and effects were assessed via mass spectrometry-based global proteomics. In prostate stromal cells, environmentally relevant levels of mono(2-ethylhexyl) phthalate (MEHP), alone and in combination with perfluorooctanesulfonic acid, led to significant changes in proteins involved in key processes underlying prostatic diseases: oxidative stress defense, proteostasis, damage-associated molecular pattern signaling, and innate immune response signaling. A follow-up experiment in metastatic prostate epithelial cells showed that the occupationally relevant levels of MEHP perturbed similar processes, including lipid, cholesterol, steroid, and alcohol metabolism; apoptosis and coagulation regulation; wound response; and aging. This work shows that environmental exposures may contribute to prostatic diseases by perturbing key processes of a proposed adverse outcome pathway, including lipid metabolism, oxidative stress, and inflammation. Future in vivo research will investigate the role of contaminants in prostatic diseases and in preventative agents.

Citation

Samuel Thomas, William A Ricke, Lingjun Li. Toxicoproteomics of Mono(2-ethylhexyl) phthalate and Perfluorooctanesulfonic Acid in Models of Prostatic Diseases. Chemical research in toxicology. 2023 Feb 20;36(2):251-259

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PMID: 36749316

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