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Dibutyl Phthalate (DBP)-Induced Apoptosis and Neurotoxicity are Mediated via the Aryl Hydrocarbon Receptor (AhR) but not by Estrogen Receptor Alpha (ERα), Estrogen Receptor Beta (ERβ), or Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) in Mouse Cortical Neurons
- Source :
- Neurotoxicity Research
- Publication Year :
- 2017
-
Abstract
- Dibutyl phthalate (di-n-butyl phthalate, DBP) is one of the most commonly used phthalate esters. DBP is widely used as a plasticizer in a variety of household industries and consumer products. Because phthalates are not chemically bound to products, they can easily leak out to enter the environment. DBP can pass through the placental and blood–brain barriers due to its chemical structure, but little is known about its mechanism of action in neuronal cells. This study demonstrated the toxic and apoptotic effects of DBP in mouse neocortical neurons in primary cultures. DBP stimulated caspase-3 and LDH activities as well as ROS formation in a concentration (10 nM–100 µM) and time-dependent (3–48 h) manner. DBP induced ROS formation at nanomolar concentrations, while it activated caspase-3 and LDH activities at micromolar concentrations. The biochemical effects of DBP were accompanied by decreased cell viability and induction of apoptotic bodies. Exposure to DBP reduced Erα and Pparγ mRNA expression levels, which were inversely correlated with protein expression of the receptors. Treatment with DBP enhanced Ahr mRNA expression, which was reflected by the increased AhR protein level observed at 3 h after exposure. ERα, ERβ, and PPARγ antagonists stimulated DBP-induced caspase-3 and LDH activities. AhR silencing demonstrated that DBP-induced apoptosis and neurotoxicity are mediated by AhR, which is consistent with the results from DBP-induced enhancement of AhR mRNA and protein expression. Our study showed that AhR is involved in DBP-induced apoptosis and neurotoxicity, while the ERs and PPARγ signaling pathways are impaired by the phthalate.
- Subjects :
- 0301 basic medicine
Time Factors
genetic structures
PPARγ
Peroxisome proliferator-activated receptor
Apoptosis
010501 environmental sciences
Toxicology
01 natural sciences
DBP
Mice
chemistry.chemical_compound
ERβ
Receptor
Cells, Cultured
ERα
Cerebral Cortex
Neurons
chemistry.chemical_classification
biology
Caspase 3
General Neuroscience
Phthalate
Dibutyl Phthalate
Original Article
Signal transduction
circulatory and respiratory physiology
medicine.medical_specialty
Cell Survival
Dibutyl phthalate
Neuroscience(all)
03 medical and health sciences
Internal medicine
medicine
Animals
Estrogen Receptor beta
RNA, Messenger
cardiovascular diseases
Estrogen receptor beta
0105 earth and related environmental sciences
Dose-Response Relationship, Drug
AhR
Estrogen Receptor alpha
Neuron
Aryl hydrocarbon receptor
PPAR gamma
030104 developmental biology
Endocrinology
Receptors, Aryl Hydrocarbon
chemistry
biology.protein
Reactive Oxygen Species
Estrogen receptor alpha
Subjects
Details
- Language :
- English
- ISSN :
- 10298428
- Volume :
- 31
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Neurotoxicity Research
- Accession number :
- edsair.doi.dedup.....885eb18e20c0e1e3535e4a2730f0d1b7