TY - JOUR
T1 - Neurotrophins and cholinergic enzyme regulated by calpain-2
T2 - New insights into neuronal apoptosis induced by polybrominated diphenyl ether-153
AU - Zhang, Hongmei
AU - Yang, Xiaorong
AU - Zhang, Huajun
AU - Li, Xin
AU - Zhang, Zhihong
AU - Hou, Lifang
AU - Wang, Zemin
AU - Niu, Qiao
AU - Wang, Tong
N1 - Funding Information:
This work received the financial support from the National Natural Science Foundation of China ( 81001258 , 31000481 ), Science and Technology Innovation Project of Shanxi Province ( 2016155 ), Research Project Supported by Shanxi Scholarship Council of China ( 2017-059 ), Shanxi Provincial Foundation for Leaders of Disciplines in Science , China (2011), Natural Science Foundation of Shanxi Province , China ( 2013021033-3 , 2011011040-2 ) and 131 Leading Talent Project of Shanxi Province , China (2013).
Publisher Copyright:
© 2018
PY - 2018/7
Y1 - 2018/7
N2 - Polybrominated diphenyl ether-153 (BDE-153) has been demonstrated to induce neuronal apoptosis in rat cerebral cortex and primary neurons. Neurotrophins and cholinergic enzymes play critical roles in the neuronal survival, maintenance, synaptic plasticity and learning memory, however, their roles in neuronal apoptosis following the BDE-153 treatment remain unclear. In this study, we firstly explored the possible predominant pathway underlying the neuronal apoptotic induced by the BDE-153 treatment in rat cerebral cortex, by measuring expression levels (mRNA and protein) of p53, caspase-3, 8, 9, calpain-1, and calpain-2, detected the levels (protein contents and mRNA) of neurotrophins including brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), and measured acetylcholinesterase (AchE) and choline acetyltransferase (ChaT) activities in rat cerebral cortex and primary neurons following BDE-153 treatment with or without pretreatment with inhibitors. Results showed that the neuronal apoptosis induced by BDE-153 was dependent on p53, and dependent on more calpain-2 than caspase-3 in the cerebral cortex of rats. Following the BDE-153 treatment, the protein contents and mRNA levels of BDNF, GDNF, NGF, NT-3, and NT-4, as well as the AchE and ChaT activities were significantly decreased in the cerebral cortex and primary neurons when compared to the untreated group. When pretreated primary neurons with calpain inhibitor PD150606 or cyclin-dependent kinase (cdk5, the downstream complex of calpain) inhibitor Roscovitine, the neurotrophins contents and activities of ChaT and AchE were reverted, along with the improvement of neuron survival compared with BDE-153 treatment alone. We conclude that neurotrophins and cholinergic enzymes were regulated by the calpain-2 activation and its downstream cdk5 pathway, and which was involved in the neuronal apoptosis induced by the BDE-153 treatment.
AB - Polybrominated diphenyl ether-153 (BDE-153) has been demonstrated to induce neuronal apoptosis in rat cerebral cortex and primary neurons. Neurotrophins and cholinergic enzymes play critical roles in the neuronal survival, maintenance, synaptic plasticity and learning memory, however, their roles in neuronal apoptosis following the BDE-153 treatment remain unclear. In this study, we firstly explored the possible predominant pathway underlying the neuronal apoptotic induced by the BDE-153 treatment in rat cerebral cortex, by measuring expression levels (mRNA and protein) of p53, caspase-3, 8, 9, calpain-1, and calpain-2, detected the levels (protein contents and mRNA) of neurotrophins including brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), and measured acetylcholinesterase (AchE) and choline acetyltransferase (ChaT) activities in rat cerebral cortex and primary neurons following BDE-153 treatment with or without pretreatment with inhibitors. Results showed that the neuronal apoptosis induced by BDE-153 was dependent on p53, and dependent on more calpain-2 than caspase-3 in the cerebral cortex of rats. Following the BDE-153 treatment, the protein contents and mRNA levels of BDNF, GDNF, NGF, NT-3, and NT-4, as well as the AchE and ChaT activities were significantly decreased in the cerebral cortex and primary neurons when compared to the untreated group. When pretreated primary neurons with calpain inhibitor PD150606 or cyclin-dependent kinase (cdk5, the downstream complex of calpain) inhibitor Roscovitine, the neurotrophins contents and activities of ChaT and AchE were reverted, along with the improvement of neuron survival compared with BDE-153 treatment alone. We conclude that neurotrophins and cholinergic enzymes were regulated by the calpain-2 activation and its downstream cdk5 pathway, and which was involved in the neuronal apoptosis induced by the BDE-153 treatment.
KW - Calpain-2
KW - Cholinergic enzyme
KW - Neuronal apoptosis
KW - Neurotrophins
KW - Polybrominated diphenyl ethers-153
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U2 - 10.1016/j.toxlet.2018.03.033
DO - 10.1016/j.toxlet.2018.03.033
M3 - Article
C2 - 29621559
AN - SCOPUS:85045466682
VL - 291
SP - 29
EP - 38
JO - Toxicology Letters
JF - Toxicology Letters
SN - 0378-4274
ER -