Dexmedetomidine Alleviates Lipopolysaccharide-Induced Hippocampal Neuronal Apoptosis via Inhibiting the p38 MAPK/c-Myc/CLIC4 Signaling Pathway in Rats
| Autor: | Jiuyan Zhang, Mingxian Shi, Honggang Fan, Jiucheng Wang, Chuqiao Wang, Yongping Chen, Lin Li, Hailin Cui |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
Male MAPK/ERK pathway MAP Kinase Signaling System p38 mitogen-activated protein kinases Neuroscience (miscellaneous) Apoptosis Hippocampus PC12 Cells Neuroprotection Proto-Oncogene Proteins c-myc Rats Sprague-Dawley Random Allocation Cellular and Molecular Neuroscience Chloride Channels Annexin polycyclic compounds Animals Neurons biology Chemistry Cytochrome c Mitochondria Rats Cell biology Neurology biology.protein Cytokines Tumor necrosis factor alpha Signal transduction Apoptosis Regulatory Proteins Dexmedetomidine hormones hormone substitutes and hormone antagonists |
| Zdroj: | Molecular Neurobiology. 58:5533-5547 |
| ISSN: | 1559-1182 0893-7648 |
| DOI: | 10.1007/s12035-021-02512-9 |
| Popis: | Dexmedetomidine (DEX) has multiple biological effects. Here, we investigated the neuroprotective role and molecular mechanism of DEX against lipopolysaccharide (LPS)-induced hippocampal neuronal apoptosis. Sprague Dawley rats were intraperitoneally injected with LPS (10 mg/kg) and/or DEX (30 µg/kg). We found that DEX improved LPS-induced alterations of hippocampal microstructure (necrosis and neuronal loss in the CA1 and CA3 regions) and ultrastructure (mitochondrial damage). DEX also attenuated LPS-induced inflammation and hippocampal apoptosis by inhibiting the increase of interleukin-1β, interleukin-6, interleukin-18, and tumor necrosis factor-α levels and downregulating the expression of mitochondrial apoptosis pathway-related proteins. Moreover, DEX prevented the LPS-induced activation of the c-Myc/chloride intracellular channel 4 (CLIC4) pathway. DEX inhibited the p38 MAPK pathway, but not JNK and ERK. To further clarify whether DEX alleviated LPS-induced neuronal apoptosis through the p38 MAPK/c-Myc/CLIC4 pathway, we treated PC12 cells with p38 MAPK inhibitor SB203582 (10 µM). DEX had the same effect as SB203582 in reducing the protein and mRNA expression of c-Myc and CLIC4. Furthermore, DEX and SB203582 diminished LPS-induced apoptosis, indicated by decreased Bax and Tom20 fluorescent double-stained cells, reduced annexin V-FITC/PI apoptosis rate, and reduced protein expression levels of Bax, cytochrome C, cleaved caspase-9, and cleaved caspase-3. Taken together, the findings indicate that DEX attenuates LPS-induced hippocampal neuronal apoptosis by regulating the p38 MAPK/c-Myc/CLIC4 signaling pathway. These findings provide new insights into the mechanism of Alzheimer's disease and depression and may help aid in drug development for these diseases. |
| Databáze: | OpenAIRE |
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