Academic Journal

Melatonin Protects Against Neuronal Apoptosis via Suppression of the ATF6/CHOP Pathway in a Rat Model of Intracerebral Hemorrhage

التفاصيل البيبلوغرافية
العنوان: Melatonin Protects Against Neuronal Apoptosis via Suppression of the ATF6/CHOP Pathway in a Rat Model of Intracerebral Hemorrhage
المؤلفون: Weilin Xu, Xiaoyang Lu, Jingwei Zheng, Tao Li, Liansheng Gao, Cameron Lenahan, Anwen Shao, Jianmin Zhang, Jun Yu
المصدر: Frontiers in Neuroscience, Vol 12 (2018)
بيانات النشر: Frontiers Media S.A., 2018.
سنة النشر: 2018
المجموعة: LCC:Neurosciences. Biological psychiatry. Neuropsychiatry
مصطلحات موضوعية: intracerebral hemorrhage, mesencephalic astrocyte-derived neurotrophic factor (ATF6), CCAAT/enhancer-binding protein homologous protein (CHOP), apoptosis, secondary brain injury, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
الوصف: Neuronal apoptosis is an important factor accounting for the poor outcomes of intracerebral hemorrhage (ICH). This study first showed that inhibition of activating transcription factor 6 (ATF6) could alleviate secondary brain injury through anti-apoptosis after ICH in rats. Melatonin, ATF6 and CCAAT/enhancer-binding protein homologous protein (CHOP) siRNAs were applied in this study. Brain edema, neurological functions, blood-brain barrier (BBB) integrity were evaluated at 24 h after ICH. Western blot analysis was used to evaluate the protein level of target proteins (ATF6, CHOP, Bip, Bcl-2, Bax, and cleaved caspase-3). Reverse transcription-polymerase chain reaction (RT-PCR) was used to assess the mRNA level of ATF6, CHOP and cleaved caspase-3. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and caspase-3 immunofluorescence staining were applied to evaluate the neuronal cell death. The results suggested that the levels of ATF6 and its downstream protein, CHOP, were upregulated and reached the peak at 24 h after ICH. ATF6 was highly expressed in neurons. The administration of melatonin significantly decreased the mRNA and protein levels of ATF6, and its downstream targets, CHOP and cleaved caspase-3, but increased the Bcl-2/Bax ratio, which ameliorated the neurological functions. The CHOP siRNA significantly reversed the pro-apoptotic effect induced by the increased ATF6 level after ICH. Melatonin could protect against neuronal apoptosis via suppression of ATF6/CHOP arm of ER-stress-response pathway.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1662-453X
Relation: https://www.frontiersin.org/article/10.3389/fnins.2018.00638/full; https://doaj.org/toc/1662-453X
DOI: 10.3389/fnins.2018.00638
URL الوصول: https://doaj.org/article/46c7d79809df46c9aeacaa9c233d9df0
رقم الانضمام: edsdoj.46c7d79809df46c9aeacaa9c233d9df0
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:1662453X
DOI:10.3389/fnins.2018.00638