کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5737878 | 1614733 | 2017 | 21 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Neuron-specific SUMO knockdown suppresses global gene expression response and worsens functional outcome after transient forebrain ischemia in mice
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کلمات کلیدی
RanGAP1rCBFqPCRSUMOGFPOGDMAPK - MAPKPCA - PCAoxygen/glucose deprivation - اکسیژن / محرومیت گلوکزBrain ischemia - ایسکمی مغزPrincipal component analysis - تحلیل مولفههای اصلی یا PCAanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceRegional cerebral blood flow - جریان خون منطقه ای مغزیKEGG یا Kyoto Encyclopedia of Genes and Genomes - دایرة المعارف ژن ها و ژنوم کیوتو Kyoto Encyclopedia of Genes and Genomes - دایره المعارف ژنتیک ژن ها و ژنوم کیوتوMicroarray - ریزآرایهactivity-regulated cytoskeleton-associated protein - فعالیت پروتئین مرتبط با سیتوکسی سلولArc - قوسTransgenic mice - موش ترانس ژنیکMicroRNA - میکرو RNA MiRNA - میکروRNA، ریزآرانای، miRNAKnockdown - نابودیGene ontology - هستیشناسی ژنیquantitative real-time PCR - واکنش زنجیره ای پلیمراز واقعی در زمان واقعیgreen fluorescent protein - پروتئین فلورسنت سبزmitogen-activated protein kinase - پروتئین کیناز فعال با mitogensmall ubiquitin-like modifier - کوچک مانند ubiquitin مانند اصلاح کننده
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
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چکیده انگلیسی
Small ubiquitin-like modifier (SUMO) conjugation (SUMOylation) plays key roles in neurologic function in health and disease. Neuronal SUMOylation is essential for emotionality and cognition, and this pathway is dramatically activated in post-ischemic neurons, a neuroprotective response to ischemia. It is also known from cell culture studies that SUMOylation modulates gene expression. However, it remains unknown how SUMOylation regulates neuronal gene expression in vivo, in the physiologic state and after ischemia, and modulates post-ischemic recovery of neurologic function. To address these important questions, we used a SUMO1-3 knockdown (SUMO-KD) mouse in which a Thy-1 promoter drives expression of 3 distinct microRNAs against SUMO1-3 to silence SUMO expression specifically in neurons. Wild-type and SUMO-KD mice were subjected to transient forebrain ischemia. Microarray analysis was performed in hippocampal CA1 samples, and neurologic function was evaluated. SUMOylation had opposite effects on neuronal gene expression before and after ischemia. In the physiological state, most genes regulated by SUMOylation were up-regulated in SUMO-KD compared to wild-type mice. Brain ischemia/reperfusion significantly modulated the expression levels of more than 400 genes in wild-type mice, with a majority of those genes upregulated. The extent of this post-ischemic transcriptome change was suppressed in SUMO-KD mice. Moreover, SUMO-KD mice exhibited significantly worse functional outcome. This suggests that suppression of global gene expression response in post-ischemic brain due to SUMO knockdown has a negative effect on post-ischemic neurologic function. Together, our data provide a basis for future studies to mechanistically link SUMOylation to neurologic function in health and disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 343, 20 February 2017, Pages 190-212
Journal: Neuroscience - Volume 343, 20 February 2017, Pages 190-212
نویسندگان
Lin Zhang, Xiaozhi Liu, Huaxin Sheng, Shuai Liu, Ying Li, Julia Q. Zhao, David S. Warner, Wulf Paschen, Wei Yang,