1. The p38 MAPK/NF-κB pathway mediates GLT-1 up-regulation during cerebral ischemic preconditioning-induced brain ischemic tolerance in rats.
- Author
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Sun YW, Zhang LY, Gong SJ, Hu YY, Zhang JG, Xian XH, Li WB, and Zhang M
- Subjects
- Animals, CA1 Region, Hippocampal pathology, Excitatory Amino Acid Transporter 2 antagonists & inhibitors, Imidazoles pharmacology, Kainic Acid analogs & derivatives, Kainic Acid pharmacology, MAP Kinase Signaling System drug effects, Male, NF-kappa B antagonists & inhibitors, NF-kappa B p50 Subunit metabolism, Neuroprotection, Nitriles pharmacology, Pyridines pharmacology, Rats, Rats, Wistar, Sulfones pharmacology, Transcription Factor RelA metabolism, p38 Mitogen-Activated Protein Kinases, Brain Ischemia genetics, Excitatory Amino Acid Transporter 2 biosynthesis, Excitatory Amino Acid Transporter 2 genetics, Ischemic Preconditioning, MAP Kinase Signaling System genetics, NF-kappa B genetics
- Abstract
Our previous finding suggests that p38 MAPK contributes to the GLT-1 upregulation during induction of brain ischemic tolerance by cerebral ischemic preconditioning (CIP), however, the underlying mechanism is still unclear. Here, we investigated the molecular mechanisms underlying the CIP-induced GLT-1 upregulation by using Western blotting, Co-immunoprecipitation (Co-IP), electrophoretic mobility shift assay (EMSA) and thionin staining in rat hippocampus CA1 subset. We found that application of BAY11-7082 (an inhibitor of NF-κB), or dihydrokainate (an inhibitor of GLT-1), or SB203580 (an inhibitor of p38 MAPK) could attenuate the CIP-induced neuronal protection in hippocampus CA1 region of rats. Moreover, CIP caused rapid activation of NF-κB, as evidenced by nuclear translocation of NF-κB p50 protein, which led to active p50/p65 dimer formation and increased DNA binding activity. GLT-1 was also increased after CIP. Pretreatment with BAY11-7082 blocked the CIP-induced GLT-1 upregulation. The above results suggest that NF-κB participates in GLT-1 up-regulation during the induction of brain ischemic tolerance by CIP. We also found that pretreatment with SB203580 caused significant reduction of NF-κB p50 protein in nucleus, NF-κB p50/p65 dimer nuclear translocation and DNA binding activity of NF-κB. Together, we conclude that p38 MAPK/NF-κB pathway participates in the mediation of GLT-1 up-regulation during the induction of brain ischemic tolerance induced by CIP., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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