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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2007-12-6
pubmed:abstractText
The aim of this study was to clarify whether 12-lipoxygenase (12-LOX) activation was involved in reactive oxygen species (ROS) generation, extensive poly(ADP-ribose) polymerase (PARP) activation and neuronal death induced by glucose-deprivation, followed by glucose-reload (GD/R). The decrease of neuronal viability and accumulation of poly(ADP-ribose) induced by GD/R were prevented 3-aminobenzamide, a representative PARP inhibitor, demonstrating this treatment protocol caused the same oxidative stress with the previously reported one. The PARP activation, ROS generation and decrease of neuron viability induced by GD/R treatment were almost completely abolished by an extracellular zinc chelator, CaEDTA. p47(phox), a cytosolic component of NADPH oxidase was translocated the membrane fraction by GD/R, indicating its activation, but it did not generate detectable ROS. Surprisingly, pharmacological inhibition of NADPH oxidase with apocynin and AEBSF further decreased the decreased neuron viability induced by GD/R. On the other hand, AA861, a 12-LOX inhibitor, prevented ROS generation and decrease of neuron viability caused by GD/R. Interestingly, an antioxidant, N-acetyl-l-cysteine rescued the neurons from GD/R-induced oxidative stress, implying effectiveness of antioxidant administration. These findings suggested that activation of 12-LOX, but not NADPH oxidase, following to zinc release might play an important role in ROS generation and decrease of viability in GD/R-treated neurons.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0304-3940
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
429
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
120-5
pubmed:meshHeading
pubmed-meshheading:17977660-Animals, pubmed-meshheading:17977660-Antioxidants, pubmed-meshheading:17977660-Arachidonate 12-Lipoxygenase, pubmed-meshheading:17977660-Brain, pubmed-meshheading:17977660-Brain Ischemia, pubmed-meshheading:17977660-Cell Survival, pubmed-meshheading:17977660-Cells, Cultured, pubmed-meshheading:17977660-Chelating Agents, pubmed-meshheading:17977660-Enzyme Activation, pubmed-meshheading:17977660-Enzyme Inhibitors, pubmed-meshheading:17977660-Glucose, pubmed-meshheading:17977660-Hypoglycemia, pubmed-meshheading:17977660-NADPH Oxidase, pubmed-meshheading:17977660-Neurons, pubmed-meshheading:17977660-Oxidative Stress, pubmed-meshheading:17977660-Poly(ADP-ribose) Polymerases, pubmed-meshheading:17977660-Rats, pubmed-meshheading:17977660-Reactive Oxygen Species, pubmed-meshheading:17977660-Zinc
pubmed:year
2007
pubmed:articleTitle
Possible involvement of 12-lipoxygenase activation in glucose-deprivation/reload-treated neurons.
pubmed:affiliation
Department of Environmental Biochemistry, Kyoto Pharmaceutical University, Misasagi, Kyoto 607-8414, Japan. nagasawa@mb.kyoto-phu.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't