Up-regulation of brain-enriched miR-107 promotes excitatory neurotoxicity through down-regulation of glutamate transporter-1 expression following ischaemic stroke
| العنوان: | Up-regulation of brain-enriched miR-107 promotes excitatory neurotoxicity through down-regulation of glutamate transporter-1 expression following ischaemic stroke |
|---|---|
| المؤلفون: | Zhen Zhang, Jie Yang, Huan Yang, Shu-Yu Li, Xiu-Ju Luo, Ting-Bo Li, Zheng Lou, Zhong-Bao Yang, Jun Peng |
| المصدر: | Clinical Science. 127:679-689 |
| بيانات النشر: | Portland Press Ltd., 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Cell, Excitotoxicity, Down-Regulation, Glutamic Acid, Apoptosis, Biology, medicine.disease_cause, Brain Ischemia, Rats, Sprague-Dawley, Downregulation and upregulation, Internal medicine, microRNA, medicine, Animals, Humans, RNA, Antisense, Neurotoxicity, Glutamate receptor, Brain, General Medicine, Middle Aged, medicine.disease, Cell Hypoxia, Rats, Up-Regulation, Surgery, Stroke, MicroRNAs, medicine.anatomical_structure, Endocrinology, Excitatory Amino Acid Transporter 2, Excitatory postsynaptic potential, Female, RNA Interference |
| الوصف: | Recent studies have uncovered that accumulation of glutamate after ischaemic stroke is closely associated with the down-regulation of glutamate transporter-1 (GLT-1) expression, suggesting that GLT-1 expression critically controls glutamate accumulation and the abnormal glutamate transport-elicited neuronal cell excitotoxicity in patients with ischaemic stroke. However, it remains unknown how GLT-1 expression is regulated under ischaemic stroke conditions. In the present study, we screened the expression of nine brain-specific or brain-enriched miRNAs in a focal cerebral ischaemia/reperfusion (I/R) injury rat model, which showed glutamate accumulation and down-regulated GLT-1 expression as expected, and revealed that the miR-107 level was elevated in both brain tissue and plasma in the model. Next, we examined the functional relationship of miR-107 with GLT-1 expression in a nerve cell hypoxia/reoxygenation (H/R) injury model. H/R treatment increased apoptosis of the nerve cells concomitant with glutamate accumulation, miR-107 elevation and suppressed GLT-1 expression, mimicking our in vivo findings in the cerebral I/R injury rat model in vitro. Co-treating the cells with an miR-107 inhibitor blocked all of the effects, demonstrating that miR-107 functions to inhibit GLT-1 expression and elevate glutamate accumulation. To extend these animal and cell-based studies to clinical patients, we measured the plasma levels of miR-107 and glutamate, and observed that both miR-107 and glutamate were elevated in patients with ischaemic stroke. On the basis of these observations, we conclude that elevated miR-107 expression after ischaemic stroke accounts, at least partially, for glutamate accumulation through suppression of GLT-1 expression. Our findings also highlight that the plasma level of miR-107 may serve as a novel biomarker for monitoring excitotoxicity in patients with ischaemic stroke. |
| تدمد: | 1470-8736 0143-5221 |
| DOI: | 10.1042/cs20140084 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5d1e086b8f204f0b5b7f71a2c5763411 https://doi.org/10.1042/cs20140084 |
| رقم الانضمام: | edsair.doi.dedup.....5d1e086b8f204f0b5b7f71a2c5763411 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14708736 01435221 |
|---|---|
| DOI: | 10.1042/cs20140084 |