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• W2078123609 abstract "Abstract Oxidative stress is associated with the pathology of acute and chronic neurodegenerative disease. We have cloned a human neuroglobin (Nb) construct and over‐expressed this protein in cultured human neuronal cells to assess whether Nb ameliorates the cellular response to experimental hypoxia‐reoxygenation (H/R) injury. Parental cells transfected with a blank (pDEST40) vector responded to H/R injury with a significant decrease in cellular ATP at 5 and 24 h after insult. This was coupled with increases in the cytosolic Ca 2+ , and the transition metals iron (Fe), copper (Cu), and zinc (Zn) within the cell body, as monitored simultaneously using X‐ray fluorescence microprobe imaging. Parental cell viability decreased over the same time period with a ∼4 to 5‐fold increase in cell death (maximum ∼25%) matched by an increase in caspase 3/7 activation (peaking at a 15‐fold increase after 24 h) and condensation of β‐actin along axonal processes. Over‐expression of Nb inhibited ATP loss and except for significant decreases in the sulfur (S), chlorine (Cl), potassium (K) and Ca 2+ contents, maintained cellular ion homeostasis after H/R insult. This resulted in increased cell viability, significantly diminished caspase activation and maintenance of the β‐actin cytoskeletal structure and receptor‐mediated endocytosis. These data indicate that bolstering the cellular content of Nb inhibits neuronal cell dysfunction promoted by H/R insult through multiple protective actions including: (i) maintenance of cellular bioenergetics; (ii) inhibition of Ca 2+ influx; (iii) a reduction in cellular uptake of Fe, Cu and Zn at the expense of S, Cl and K; and (iv) an enhancement of cell viability through inhibiting necrosis and apoptosis." @default.
• W2078123609 created "2016-06-24" @default.
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• W2078123609 date "2009-02-09" @default.
• W2078123609 modified "2023-09-29" @default.
• W2078123609 title "Multiple protective activities of neuroglobin in cultured neuronal cells exposed to hypoxia re-oxygenation injury" @default.
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• W2078123609 doi "https://doi.org/10.1111/j.1471-4159.2008.05846.x" @default.
• W2078123609 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19154338" @default.
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