title: Lambda-cyhalothrin disrupts the up-regulation effect of 17β-estradiol on post-synaptic density 95 protein expression via estrogen receptor α-dependent Akt pathway.
abstract: Lambda-cyhalothrin (LCT), one of the type II pyrethroids, has been widely used throughout the world. The estrogenic effect of LCT to increase cell proliferation has been well established. However, whether the estrogenic effect of LCT will influence neurodevelopment has not been investigated. In addition, 17β-Estradiol (E2) plays a crucial role in neurodevelopment and induces an increase in synaptic proteins. The post-synaptic density 95 (PSD95) protein, which is involved in the development of the structure and function of new spines and localized with estrogen receptor α (ERα) at the post-synaptic density (PSD), was detected in our study by using hippocampal neuron cell line HT22. We found that LCT up-regulated PSD95 and ERα expression, estrogen receptor (ER) antagonist ICI182,780 and phosphatidylinositol-4; 5-bisphosphate 3-kinase (PI3K) inhibitor LY294,002 blocked this effect. In addition, LCT disrupted the promotion effect of E2 on PSD95. To investigate whether the observed changes are caused by ERα-dependent signaling activation, we next detected the effects of LCT on the ERα-mediated PI3K-Protein kinase B (PKB/Akt)-eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) pathway. There existed an activation of Akt and the downstream factor 4E-BP1 after LCT treatment. In addition, LCT could disrupt the activation effect of E2 on the Akt pathway. However, no changes in cAMP response element-binding protein (CREB) activation and PSD95 messenger ribonucleic acid (mRNA) were observed. Our findings demonstrated that LCT could increase the PSD95 protein level via the ERα-dependent Akt pathway, and LCT might disrupt the up-regulation effect of E2 on PSD95 protein expression via this signaling pathway.
authors.affiliation: Chinese Academy of Science Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui, China; Department of Toxicology, College of Public Health, Anhui Medical University, Hefei 230032, China. Electronic address: wqn@ahmu.edu.cn.
authors.forename: Qunan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Toxicology, College of Public Health, Anhui Medical University, Hefei 230032, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Pharmacy, Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Toxicology, College of Public Health, Anhui Medical University, Hefei 230032, China.
authors.forename: Nian
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Toxicology, College of Public Health, Anhui Medical University, Hefei 230032, China.
authors.forename: Daji
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Toxicology, College of Public Health, Anhui Medical University, Hefei 230032, China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Toxicology, College of Public Health, Anhui Medical University, Hefei 230032, China.
authors.forename: Chengwei
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Maternal and Child health, College of Public Health, Anhui Medical University, Hefei 230032, China.
authors.forename: Fangbiao
authors.initials: F
authors.lastname: Tao
authors.affiliation: Chinese Academy of Science Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui, China. Electronic address: jnzhou@ustc.edu.cn.
authors.forename: Jiangning
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002460:Cell Line; D000076122:Disks Large Homolog 4 Protein; D052244:Endocrine Disruptors / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D004958:Estradiol / Q000235:genetics* / Q000378:metabolism; D005659:Fungicides, Industrial / Q000633:toxicity; D051528:Guanylate Kinases / Q000235:genetics* / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009570:Nitriles / Q000633:toxicity*; D011722:Pyrethrins / Q000633:toxicity*; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D000076122:Disks Large Homolog 4 Protein; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D004958:Estradiol; D005659:Fungicides, Industrial; D051528:Guanylate Kinases; D007306:Insecticides; D008565:Membrane Proteins; D009570:Nitriles; D011722:Pyrethrins; D011960:Receptors, Estrogen; D000097983:ERRalpha Estrogen-Related Receptor; C501447:Dlg4 protein, mouse; C037304:cyhalothrin
keywords: 17β-Estradiol; Akt pathway; Interference; Lambda-cyhalothrin; Post-synaptic density 95