The insecticide synergist piperonyl butoxide inhibits hedgehog signaling: assessing chemical risks.

Toxicological Sciences : an Official Journal of the Society of Toxicology
Jiangbo WangWei Chen

Abstract

The spread of chemicals, including insecticides, into the environment often raises public health concerns, as exemplified by a recent epidemiologic study associating in utero piperonyl butoxide (PBO) exposure with delayed mental development. The insecticide synergist PBO is listed among the top 10 chemicals detected in indoor dust; a systematic assessment of risks from PBO exposure, as for many toxicants unfortunately, may be underdeveloped when important biological targets that can cause toxicity are unknown. Hedgehog/Smoothened signaling is critical in neurological development. This study was designed to use novel high-throughput in vitro drug screening technology to identify modulators of Hedgehog signaling in environmental chemicals to assist the assessment of their potential risks. A directed library of 1408 environmental toxicants was screened for Hedgehog/Smoothened antagonist activity using a high-content assay that evaluated the interaction between Smoothened and βarrestin2 green fluorescent protein. PBO was identified as a Hedgehog/Smoothened antagonist capable of inhibiting Hedgehog signaling. We found that PBO bound Smoothened and blocked Smoothened overexpression-induced Gli-luciferase reporter activity but had no ...Continue Reading

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Citations

Oct 28, 2015·Environmental Toxicology and Chemistry·Bruno CamposCarlos Barata
Dec 3, 2016·The Science of the Total Environment·Carlos BarataKarel De Schamphelaere
Aug 9, 2020·Alcoholism, Clinical and Experimental Research·Joshua L EversonJohann K Eberhart
Jun 10, 2020·Environmental Health : a Global Access Science Source·Yonit A AddissieMaximilian Muenke
Jan 31, 2021·Reproductive Toxicology·Jeong-Won Bae, Woo-Sung Kwon
Feb 27, 2021·Frontiers in Cell and Developmental Biology·Brian P JohnsonRobert J Lipinski
Apr 28, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Hanna Katarina Lilith JohanssonTerje Svingen
Aug 29, 2019·ACS Omega·Ana Francis Carballo-ArceTony Durst

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