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Phthalates Induce Neurotoxicity by Disrupting the Mfn2-PERK Axis-Mediated Endoplasmic Reticulum-Mitochondria Interaction.
Zhao, Yi; Chang, Yuan-Hang; Ren, Hao-Ran; Lou, Ming; Jiang, Fu-Wei; Wang, Jia-Xin; Chen, Ming-Shan; Liu, Shuo; Shi, Yu-Sheng; Zhu, Hong-Mei; Li, Jin-Long.
Afiliação
  • Zhao Y; College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China.
  • Chang YH; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin 150030, P. R. China.
  • Ren HR; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin 150030, P. R. China.
  • Lou M; College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China.
  • Jiang FW; College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China.
  • Wang JX; College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China.
  • Chen MS; College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China.
  • Liu S; College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China.
  • Shi YS; College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China.
  • Zhu HM; College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China.
  • Li JL; College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China.
J Agric Food Chem ; 72(13): 7411-7422, 2024 Apr 03.
Article em En | MEDLINE | ID: mdl-38390847
ABSTRACT
Di-(2-ethylhexyl) phthalate (DEHP), as the most common phthalate, has been extensively used as a plasticizer to improve the plasticity of agricultural products, which pose severe harm to human health. Mitochondrial dynamics and endoplasmic reticulum (ER) homeostasis are indispensable for maintaining mitochondria-associated ER membrane (MAM) integrity. In this study, we aimed to explore the effect of DEHP on the nervous system and its association with the ER-mitochondria interaction. Here, we showed that DEHP caused morphological changes, motor deficits, cognitive impairments, and blood-brain barrier disruption in the brain. DEHP triggered ER stress, which is mainly mediated by protein kinase R-like endoplasmic reticulum kinase (PERK) signaling. Moreover, DEHP-induced mitofusin-2 (Mfn2) downregulation results in imbalance of the mitochondrial dynamics. Interestingly, DEHP exposure impaired MAMs by inhibiting the Mfn2-PERK interaction. Above all, this study elucidates the disruption of the Mfn2-PERK axis-mediated ER-mitochondria interaction as a phthalate-induced neurotoxicity that could be potentially developed as a novel therapy for neurological diseases.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácidos Ftálicos / Dietilexilftalato Limite: Humans Idioma: En Revista: J Agric Food Chem Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácidos Ftálicos / Dietilexilftalato Limite: Humans Idioma: En Revista: J Agric Food Chem Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos