title: Ceftriaxone Protects Astrocytes from MPP(+) via Suppression of NF-κB/JNK/c-Jun Signaling.
abstract: Ceftriaxone has been shown to attenuate the dopaminergic neuron death and alleviate behavioral disorders in Parkinson's disease models via upregulation of glutamate transporter-1 (GLT-1) and decreases in extracellular glutamate. However, details of how this neuroprotection occurs are uncertain. We hypothesized that cytoprotection by ceftriaxone in astrocytes exposed to 1-methyl-4-phenylpyridinium (MPP(+)) involves suppression of the NF-κB/JNK/c-Jun signaling pathway. Here, we observed a protective effect of ceftriaxone in primary astrocytes exposed to MPP(+). Ceftriaxone enhanced glutamate uptake and promoted primary astrocyte viability after MPP(+) exposure. Ceftriaxone enhances glutamate uptake via upregulation of GLT-1 in the plasma membrane, and alleviates MPP(+)-induced neurotoxicity via suppression of NF-κB/JNK/c-Jun signaling. Collectively, our data offer evidence that increased expression and function of GLT-1 are involved in the protective mechanism of ceftriaxone in astrocytes exposed to MPP(+) in vitro, and we offer insight into the potential therapeutic role of ceftriaxone in treatment of Parkinson's disease.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiuping
authors.initials: X
authors.lastname: Zhang
authors.forename: Shaogang
authors.initials: S
authors.lastname: Qu
mesh_terms: D015655:1-Methyl-4-phenylpyridinium; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002443:Ceftriaxone / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000378:metabolism; D007700:Kinetics; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism*; D000066829:Neuroprotection / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D018696:Neuroprotective Agents; D016755:Proto-Oncogene Proteins c-jun; D001224:Aspartic Acid; D018698:Glutamic Acid; D002443:Ceftriaxone; D015655:1-Methyl-4-phenylpyridinium
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