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https://hdl.handle.net/2440/52096
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Type: | Journal article |
Title: | Multiple protective activities of neuroglobin in cultured neuronal cells exposed to hypoxia re-oxygenation injury |
Author: | Duong, T. Witting, P. Antao, S. Parry, S. Kennerson, M. Lai, B. Vogt, S. Lay, P. Harris, H. |
Citation: | Journal of Neurochemistry, 2009; 108(5):1143-1154 |
Publisher: | Blackwell Publishing Ltd |
Issue Date: | 2009 |
ISSN: | 0022-3042 1471-4159 |
Statement of Responsibility: | Thi Thuy Hong Duong, Paul Kenneth Witting, Shane Tony Antao, Sarah Nicole Parry, Marina Kennerson, Barry Lai, Stefan Vogt, Peter Andrew Lay, and Hugh Hamlyn Harris |
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 approximately 4 to 5-fold increase in cell death (maximum approximately 25%) matched by an increase in caspase 3/7 activation (peaking at a 15-fold increase after 24 h) and condensation of beta-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 beta-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. |
Keywords: | antioxidant, apoptosis neuroglobin neuro-protection oxidative stress synchrotron radiation X-ray fluorescence imaging. |
DOI: | 10.1111/j.1471-4159.2008.05846.x |
Grant ID: | http://purl.org/au-research/grants/arc/DP0208409 http://purl.org/au-research/grants/arc/DP0664706 |
Published version: | http://dx.doi.org/10.1111/j.1471-4159.2008.05846.x |
Appears in Collections: | Aurora harvest 5 Chemistry publications Environment Institute publications |
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