IκB kinase inhibition remodeled connexins, pannexin‐1, and excitatory amino‐acid transporters expressions to promote neuroprotection of galantamine and morphine
| Autor: | Shimaa Magdy, Nivin Sharawy, Nancy F Samir, Haitham S. Mohammed, Basma Emad Aboulhoda, Maha Gamal, Laila A. Rashed |
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| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
Male 0301 basic medicine Physiology Clinical Biochemistry Anti-Inflammatory Agents Glutamic Acid Nerve Tissue Proteins IκB kinase Neuroprotection Connexins Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Glutamate homeostasis Nitriles Animals Glutamate reuptake Sulfones Neurons Morphine Galantamine Chemistry Glutamate receptor Brain Neurodegenerative Diseases Transporter Cell Biology Pannexin I-kappa B Kinase Cell biology Excitatory Amino Acid Transporter 1 Disease Models Animal Neuroprotective Agents 030104 developmental biology Excitatory Amino Acid Transporter 2 030220 oncology & carcinogenesis Excitatory postsynaptic potential Neuroglia Signal Transduction |
| Zdroj: | Journal of Cellular Physiology. 236:7516-7532 |
| ISSN: | 1097-4652 0021-9541 |
| DOI: | 10.1002/jcp.30387 |
| Popis: | Inflammatory pathway and disruption in glutamate homeostasis join at the level of the glia, resulting in various neurological disorders. In vitro studies have provided evidence that membrane proteins connexions (Cxs) are involved in glutamate release, meanwhile, excitatory amino-acid transporters (EAATs) are crucial for glutamate reuptake (clearance). Moreover, pannexin-1 (Panx-1) activation is more detrimental to neurons. Their expression patterns during inflammation and the impacts of IκB kinase (IKK) inhibition, morphine, and galantamine on the inflammatory-associated glutamate imbalance remain elusive. To investigate this, rats were injected with saline or lipopolysaccharide. Thereafter, vehicles, morphine, galantamine, and BAY-117082 were administered in different groups of animals. Subsequently, electroencephalography, enzyme-linked immunosorbent assay, western blot, and histopathological examinations were carried out and various indicators of inflammation and glutamate level were determined. Parallel analysis of Cxs, Panx-1, and EAAts in the brain was performed. Our findings strengthen the concept that unregulated expressions of Cxs, Panx-1, and EAATs contribute to glutamate accumulation and neuronal cell loss. Nuclear factor-kB (NF-κB) pathway can significantly contribute to glutamate homeostasis via modulating Cxs, Panx-1, and EAATs expressions. BAY-117082, via inhibition of IkK, promoted the anti-inflammatory effects of morphine as well as galantamine. We concluded that NF-κB is an important component of reshaping the expressions of Cxs, panx-1, and EAATs and the development of glutamate-induced neuronal degeneration. |
| Databáze: | OpenAIRE |
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