Dexmedetomidine Protects Against Chemical Hypoxia-Induced Neurotoxicity in Differentiated PC12 Cells Via Inhibition of NADPH Oxidase 2-Mediated Oxidative Stress.

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  • Additional Information
    • Source:
      Publisher: Springer Country of Publication: United States NLM ID: 100929017 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-3524 (Electronic) Linking ISSN: 10298428 NLM ISO Abbreviation: Neurotox Res Subsets: MEDLINE
    • Publication Information:
      Publication: <2009-> : New York : Springer
      Original Publication: [Amsterdam?] : Harwood Academic Publishers,
    • Subject Terms:
      Cell Hypoxia/*drug effects ; Dexmedetomidine/*pharmacology ; NADPH Oxidase 2/*metabolism ; Neuroprotective Agents/*pharmacology ; Oxidative Stress/*drug effects; Animals ; Apoptosis/drug effects ; Apoptosis/physiology ; Calcium/metabolism ; Cell Hypoxia/physiology ; Cobalt/toxicity ; Mitochondria/drug effects ; Mitochondria/metabolism ; NADPH Oxidase 2/genetics ; Neuroprotection/drug effects ; Neuroprotection/physiology ; Oxidative Stress/physiology ; PC12 Cells ; Rats
    • Abstract:
      Dexmedetomidine (Dex) is a widely used sedative in anesthesia and critical care units, and it exhibits neuroprotective activity. However, the precise mechanism of Dex-exerted neuroprotection is not clear. Increased neuronal NADPH oxidase 2 (NOX2) contributes to oxidative stress and neuronal damage in various hypoxia-related neurodegenerative disorders. The present study investigated whether Dex regulated neuronal NOX2 to exert its protective effects under hypoxic conditions. Well-differentiated PC12 cells were exposed to cobalt chloride (CoCl 2 ) to mimic a neuronal model of chemical hypoxia-mediated neurotoxicity. The data showed that Dex pretreatment of PC12 cells significantly suppressed CoCl 2 -induced neurotoxicity, as evidenced by the enhanced cell viability, restoration of cellular morphology, and reduction in apoptotic cells. Dex improved mitochondrial function and inhibited CoCl 2 -induced mitochondrial apoptotic pathways. We further demonstrated that Dex attenuated oxidative stress, downregulated NOX2 protein expression and activity, and inhibited intracellular calcium ([Ca 2+ ]i) overload in CoCl 2 -treated PC12 cells. Moreover, knockdown of the NOX2 gene markedly improved mitochondrial function and attenuated apoptosis under hypoxic conditions. These results demonstrated that the protective effects of Dex against hypoxia-induced neurotoxicity in neural cells were mediated, at least partially, via inhibition of NOX2-mediated oxidative stress.
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    • Grant Information:
      81571076 National Natural Science Foundation of China
    • Contributed Indexing:
      Keywords: Dexmedetomidine; Hypoxia· NADPH oxidase 2; Oxidative stress; PC12 cells
    • Accession Number:
      0 (Neuroprotective Agents)
      3G0H8C9362 (Cobalt)
      67VB76HONO (Dexmedetomidine)
      EC 1.6.3.- (Cybb protein, rat)
      EC 1.6.3.- (NADPH Oxidase 2)
      EVS87XF13W (cobaltous chloride)
      SY7Q814VUP (Calcium)
    • Publication Date:
      Date Created: 20180817 Date Completed: 20190220 Latest Revision: 20200225
    • Publication Date:
      20231215
    • Accession Number:
      10.1007/s12640-018-9938-7
    • Accession Number:
      30112693