Supplementation with a synthetic polyphenol limits oxidative stress and enhances neuronal cell viability in response to hypoxia-re-oxygenation injury.
Oxidative stress is associated with the pathology of acute and chronic neurodegenerative disease. Cultured human neuronal cells exposed to experimental hypoxia-re-oxygenation (H/R) injury responded with an increased production of reactive oxygen species (ROS) and a significant decrease in intracellular ATP. Expression of genes encoding for hypoxia-inducible factor 1-alpha (HIF1-alpha), inducible haemoxygenase-1 (HO-1), glucose transporter-1 (Glut-1), the oxygen-sensor neuroglobin (Nb) and Cu,Zn-superoxide dismutase (SOD1), catalase (CAT) and glutathione peroxidase-1 (Gpx-1) increased significantly in response to the insult. Enhanced expression of HO-1, SOD1 and CAT correlated with an increase in the corresponding protein activity. Despite the cellular response to bolster antioxidant capacity, apoptosis and necrosis increased following H/R injury. In contrast, ROS accumulation, the endogenous gene response and cell death was limited in neuronal cells pre-incubated with 50 or 100, but not 10 microM of the phenolic antioxidant 3,3',5,5'-tetra-t-butyl-biphenyl-4,4'-diol (BP) prior to H/R injury. These data indicate that the early endogenous gene response to H/R injury is unable to inhibit neuronal dysfunction and that increasing cellular antioxidant capacity with a synthetic polyphenol (>10 microM) is potentially neuro-protective.
Vascular Biology Group, ANZAC Research Institute, Concord Hospital, Concord, NSW 2139, Australia.
T T Hong
TT
Duong
Shane
S
Antao
Natasha A
NA
Ellis
Simon J
SJ
Myers
Paul K
PK
Witting
D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D017302:Annexins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002454:Cell Differentiation; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000008:administration & dosage* / Q000737:chemistry; D019922:GAP-43 Protein / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D006931:Hyperbaric Oxygenation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000008:administration & dosage* / Q000737:chemistry; D059808:Polyphenols; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
D017302:Annexins; D005419:Flavonoids; D019922:GAP-43 Protein; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010636:Phenols; D059808:Polyphenols; C000606290:SOD1 protein, human; D013481:Superoxides; D000255:Adenosine Triphosphate; D002374:Catalase; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D020169:Caspases