1. The mechanism of GLT-1 mediating cerebral ischemic injury depends on the activation of p38 MAPK.
- Author
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Zhang LY, Hu YY, Zhao CC, Qi J, Su AC, Lou N, Zhang MY, Li L, Xian XH, Gong JX, Zhao H, Zhang JG, Li WB, and Zhang M
- Subjects
- Animals, Astrocytes metabolism, Brain Ischemia physiopathology, CA1 Region, Hippocampal metabolism, Cell Death, Coculture Techniques, Excitatory Amino Acid Transporter 2 physiology, Glucose metabolism, Glutamic Acid metabolism, Hippocampus metabolism, Imidazoles pharmacology, MAP Kinase Signaling System, Male, Neurons metabolism, Oxygen metabolism, Pyridines pharmacology, Rats, Rats, Wistar, Signal Transduction drug effects, p38 Mitogen-Activated Protein Kinases physiology, Brain Ischemia metabolism, Excitatory Amino Acid Transporter 2 metabolism, p38 Mitogen-Activated Protein Kinases metabolism
- Abstract
The previous studies have shown that glial glutamate transporter-1 (GLT-1) participates in cerebral ischemic injury in rats. However, the mechanism involved remains to be elucidated. This study was undertaken to investigate whether p38 MAPK was involved in regulating GLT-1 in the process. At first, it was observed that global brain ischemia for 8 min led to obvious delayed neuronal death, GLT-1 down-regulation and p-p38 MAPK up-regulation in CA1 hippocampus in rats. Then, whether p-p38 MAPK was involved in regulating GLT-1 during cerebral ischemic injury was studied in vitro. Astrocyte-neuron co-cultures exposed to oxygen and glucose deprivation (OGD) were used to mimic brain ischemia. It was observed that lethal OGD (4-h OGD) decreased GLT-1 expression and increased p-p38 MAPK expression in astrocytes. The p-p38 MAPK protein rised from 0 min to 48 h that is the end time of the observation, and the peak value was at 12 h, which was 12.45 times of the control group. Moreover, pre-administration of p38 MAPK inhibitor SB203580 or its siRNA dose-dependently increased GLT-1 expression, and meanwhile alleviated the neuronal death induced by lethal OGD. The above results indicated that p38 MAPK signaling pathway participated in regulating GLT-1 during OGD injury in vitro. Finally, back to in vivo experiment, it was found that pre-administration of SB203580 by intracerebroventricular injection dose-dependently reversed the down-regulation of GLT-1 expression and attenuated the delayed neuronal death normally induced by global brain ischemia in CA1 hippocampus in rats. Taken together, it can be concluded that the mechanism of GLT-1 mediating cerebral ischemic injury depends on the activation of p38 MAPK., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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