2. Academic Validation
  3. Tris(1,3-dichloro-2-propyl)phosphate Reduces the Lifespan via Activation of an Unconventional Insulin/Insulin-Like Growth Factor-1 Signaling Pathway

Tris(1,3-dichloro-2-propyl)phosphate Reduces the Lifespan via Activation of an Unconventional Insulin/Insulin-Like Growth Factor-1 Signaling Pathway

  • Environ Sci Technol. 2020 Sep 1;54(17):10783-10796. doi: 10.1021/acs.est.0c03630.
Chen Wang 1,  Haibo Chen 2 3,  Hui Li 1 2,  Yunchao Zhang 1,  Luyao Ren 1,  Chao Chen 4,  Xiaoli Wang 1,  Jun Yu 1,  Zongrui Li 3,  Yongdi Liu 1
Affiliations

Affiliations

  • 1 State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, School of Resources and Environmental Engineering, East China University of Science and Technology, Shanghai 200237, P. R. China.
  • 2 Institute for Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, P. R. China.
  • 3 State Environmental Protection Key Laboratory of Environmental Pollution Health Risk Assessment, South China Institute of Environmental Sciences, Ministry of Ecology and Environment, Guangzhou 510655, P. R. China.
  • 4 State Key Laboratory of Bioreactor Engineering, Biomedical Nanotechnology Center, Shanghai Collaborative Innovation Center for Biomanufacturing, School of Biotechnology, East China University of Science and Technology, Shanghai 200237, P. R. China.
PMID: 32786597 DOI: 10.1021/acs.est.0c03630
Abstract

Tris(1,3-dichloro-2-propyl)phosphate (TDCPP) is an environmental contaminant that has attracted increasing concern due to its presence in environmental media and biological samples. Our previous study demonstrated that exposure to TDCPP reduced the lifespan of Caenorhabditis elegans, but the mechanisms, including the relevant signaling pathways, are unclear. The current study found that TDCPP exposure triggers an unconventional Insulin/insulin-like growth factor signaling (IIS) pathway, not by disrupting the insulin-like growth factor-1 receptor DAF-2/IGF1R but by inhibiting the downstream tumor-suppressor factor DAF-18/PTEN. This inhibition reduces PI(3,4,5)P3 (PIP3) dephosphorylation, causing buildup that increases the activation of the Akt/Protein Kinase B (PKB) family of serine/threonine kinases. This activation induces DAF-16/FoxO phosphorylation and promotes the sequestration of DAF-16/FoxO in the cytoplasm, reducing the lifespan of nematodes. Our results have important diagnostic and therapeutic implications for controlling TDCPP-related diseases, especially those originating with IIS pathway components.

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