Linked Life Data

11090611

Source:http://linkedlifedata.com/resource/pubmed/id/11090611

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2001-1-4
pubmed:abstractText
Zinc overload may be a key mechanism of neuronal death in acute brain injury. We have demonstrated previously that zinc overload neurotoxicity involves protein kinase C (PKC)-dependent rises in intracellular levels of reactive oxygen species (ROS). However, the cascade linking PKC activation to ROS generation in cultured cortical neurons has been unknown. A recent study has demonstrated that ROS-generating NADPH oxidase is present in sympathetic neurons and contributes to NGF deprivation-induced cell death. Because NADPH oxidase is activated by PKC, in the present study, we examined the possibility that NADPH oxidase is the effector for oxidative stress in zinc-overloaded cortical cells. Reverse transcription-PCR and Western blot analyses revealed that naive cultured cortical cells express subunits of NADPH oxidase at low levels. Exposure to zinc substantially increased levels of NADPH oxidase subunits in both neurons and astrocytes. In addition, zinc exposure induced translocation of the p47(PHOX) and p67(PHOX) subunits to the membrane, a signature event for NADPH oxidase activation. Addition of a selective PKC inhibitor, GF109203X, blocked both the induction and the membrane translocation of NADPH oxidase by zinc. Supporting the role for NADPH oxidase in zinc-triggered oxidative injury, NADPH oxidase inhibitors attenuated ROS production and cortical neuronal death induced by zinc. In addition, Cu/Zn-superoxide dismutase and catalase attenuated zinc-induced cortical neuronal death. Our results have demonstrated that zinc overload induces and activates NADPH oxidase in cortical neurons and astrocytes in a PKC-dependent manner. Thus, NADPH oxidase may be an enzyme contributing to ROS generation in zinc-overloaded cortical neurons and astrocytes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
RC111
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11090611-Animals, pubmed-meshheading:11090611-Astrocytes, pubmed-meshheading:11090611-Catalase, pubmed-meshheading:11090611-Cell Death, pubmed-meshheading:11090611-Cell Membrane, pubmed-meshheading:11090611-Cells, Cultured, pubmed-meshheading:11090611-Cerebral Cortex, pubmed-meshheading:11090611-Coculture Techniques, pubmed-meshheading:11090611-Enzyme Activation, pubmed-meshheading:11090611-Enzyme Induction, pubmed-meshheading:11090611-Enzyme Inhibitors, pubmed-meshheading:11090611-Mice, pubmed-meshheading:11090611-NADPH Oxidase, pubmed-meshheading:11090611-Neurons, pubmed-meshheading:11090611-Oxidative Stress, pubmed-meshheading:11090611-Phosphoproteins, pubmed-meshheading:11090611-Protein Kinase C, pubmed-meshheading:11090611-Protein Subunits, pubmed-meshheading:11090611-Protein Transport, pubmed-meshheading:11090611-Reactive Oxygen Species, pubmed-meshheading:11090611-Superoxide Dismutase, pubmed-meshheading:11090611-Zinc
pubmed:year
2000
pubmed:articleTitle
Induction and activation by zinc of NADPH oxidase in cultured cortical neurons and astrocytes.
pubmed:affiliation
National Creative Research Initiative Center for the Study of CNS Zinc and Department of Neurology, University of Ulsan College of Medicine, Seoul 138-736, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't