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dc.contributor.authorThorburn, Cassandra
dc.contributor.authorKim, Benjamin
dc.contributor.authorPanchenko, Michael
dc.contributor.authorAbrha, Aser
dc.contributor.authorKhalil, Ahmed
dc.contributor.authorSuvorov, Alexander
dc.date2022-08-11T08:08:15.000
dc.date.accessioned2022-08-23T15:48:02Z
dc.date.available2022-08-23T15:48:02Z
dc.date.issued2016-05-20
dc.date.submitted2016-07-20
dc.identifier.doi10.13028/22jr-pw06
dc.identifier.urihttp://hdl.handle.net/20.500.14038/28123
dc.description.abstractMammalian target of rapamycin (mTOR), also known as mechanistic target of rapamycin, is a known metabolic master-switch. In conditions of starvation, mTOR suppresses biosynthetic programs and increases the recycling of proteins and organelles. Upon stimulation by nutrients and growth factors, however, mTOR causes activation of biosynthesis and suppression of autophagy. The mTOR-centered molecular pathway is a major pathway of growth regulation and metabolism, linked to aging and the development of cancer, obesity, type 2 diabetes, neurodevelopmental and neurodegenerative diseases. Currently, the role of environmental factors in the modulation of the mTOR pathway remains largely unknown. The present study suggests that perinatal exposure to environmentally-relevant doses of polybrominated diphenyl ethers (PBDEs), a group of ubiquitous flame-retardants, results in long-lasting reprogramming of the mTOR pathway in mouse liver. This reprogramming includes suppression of mTORC1 and mTORC2 activity, accompanied by coordinated up-regulation of protein synthesis machinery and increased concentrations of circulating IGF-1. Further, experiments with MCF-7 breast cancer cells demonstrate that exposure to PBDEs results in fast induction of the REDD1/DDIT4 gene – a potent suppressor of mTORC1. This data indicates that the response of liver tissue to PBDE exposure during this critical developmental window is a dynamic process, and is likely triggered via a REDD1-dependent mechanism, ultimately resulting in long-lasting changes in the metabolic profile of the tissue. This study suggests that environmental exposures to brominated flame retardants may have profound and long-term effects on the central regulation hub of metabolic health, and may be implicated in the pathogenesis of the most relevant diseases of modern society.
dc.formatyoutube
dc.language.isoen_US
dc.rightsCopyright the Author(s)
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/
dc.subjectrapamycin
dc.subjectbrominated flame retardants
dc.subjectmeabolic health
dc.subjectChemical and Pharmacologic Phenomena
dc.subjectEnvironmental Health
dc.subjectEnvironmental Public Health
dc.subjectMedical Toxicology
dc.titleReprogramming of mTOR Signaling by Perinatal Exposure to Brominated Flame Retardant
dc.typePoster Abstract
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1450&context=cts_retreat&unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/cts_retreat/2016/posters/85
dc.identifier.contextkey8855645
refterms.dateFOA2022-08-23T15:48:02Z
html.description.abstract<p>Mammalian target of rapamycin (mTOR), also known as mechanistic target of rapamycin, is a known metabolic master-switch. In conditions of starvation, mTOR suppresses biosynthetic programs and increases the recycling of proteins and organelles. Upon stimulation by nutrients and growth factors, however, mTOR causes activation of biosynthesis and suppression of autophagy. The mTOR-centered molecular pathway is a major pathway of growth regulation and metabolism, linked to aging and the development of cancer, obesity, type 2 diabetes, neurodevelopmental and neurodegenerative diseases. Currently, the role of environmental factors in the modulation of the mTOR pathway remains largely unknown. The present study suggests that perinatal exposure to environmentally-relevant doses of polybrominated diphenyl ethers (PBDEs), a group of ubiquitous flame-retardants, results in long-lasting reprogramming of the mTOR pathway in mouse liver. This reprogramming includes suppression of mTORC1 and mTORC2 activity, accompanied by coordinated up-regulation of protein synthesis machinery and increased concentrations of circulating IGF-1. Further, experiments with MCF-7 breast cancer cells demonstrate that exposure to PBDEs results in fast induction of the REDD1/DDIT4 gene – a potent suppressor of mTORC1. This data indicates that the response of liver tissue to PBDE exposure during this critical developmental window is a dynamic process, and is likely triggered via a REDD1-dependent mechanism, ultimately resulting in long-lasting changes in the metabolic profile of the tissue. This study suggests that environmental exposures to brominated flame retardants may have profound and long-term effects on the central regulation hub of metabolic health, and may be implicated in the pathogenesis of the most relevant diseases of modern society.</p>
dc.identifier.submissionpathcts_retreat/2016/posters/85


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