Edaravone protects rat astrocytes from oxidative or neurotoxic inflammatory insults by restoring Akt/Bcl-2/Caspase-3 signaling axis
| Autor: | Xi-Xi Li, Zhe Guo, Rongfeng Lan, Huan-Tong Wu, Xiao-Yan Qin, Run-Ze Gu, Yun Yu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Central nervous system free radical scavenger Caspase 3 medicine.disease_cause C1q complement component 1q CNS central nervous system Neuroprotection Article lcsh:RC321-571 TLRs Toll-like receptors IL-1α interleukin 1 alpha 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Edaravone oxidative stress TNF-α tumor necrosis factor alpha NOS2 nitric oxide synthase 2 Protein kinase B lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry edaravone GFAP General Neuroscience GFAP glial fibrillary acidic protein Free radical scavenger ALS amyotrophic lateral sclerosis pro-inflammatory factors Cell biology IL-6 interleukin 6 030104 developmental biology medicine.anatomical_structure chemistry Apoptosis H2O2 hydrogen peroxide TNF-α LPS lipopolysaccharides IL-1β interleukin 1beta 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | IBRO Reports IBRO Reports, Vol 8, Iss, Pp 122-128 (2020) |
| ISSN: | 2451-8301 |
| Popis: | Astrocytes are the major glia cells in the central nervous system (CNS). Increasing evidence indicates that more than to be safe-guard and supporting cells for neurons, astrocytes play a broad spectrum of neuroprotective and pathological functions. Thus, they are compelling models to decipher mechanistic insights of glia cells to CNS insults and for the development of drugs. Edaravone is a free radical scavenger with the capacity to eliminate hydroxyl radicals and lipid peroxides. In this study, we examined the neuroprotective effects of edaravone in rat astrocytes challenged by hydrogen peroxide (H2O2) or bacterial lipopolysaccharides (LPS), respectively. We discovered that edaravone attenuated H2O2-induced oxidative stress by reactivating the Akt signaling axis and antagonistically restoring the expression of apoptosis associated regulators such as Bcl-2 and Caspase-3. Consistently, inhibition of Akt signaling by LY294002 attenuated the anti-oxidative activity of edaravone. In addition, edaravone mitigated LPS-induced morphological changes in astrocytes and alleviated the inflammatory activation and expression of TNF-α, IL-1β, IL-6 and NOS2. In summary, our data suggested that edavarone effectively protects astrocytes from oxidative stress or infectious insults, which may pave a new avenue for its application in preclinical research and human disease therapeutics. |
| Databáze: | OpenAIRE |
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