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rdf:type |
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lifeskim:mentions |
umls-concept:C0011065,
umls-concept:C0020616,
umls-concept:C0028128,
umls-concept:C0030685,
umls-concept:C0038836,
umls-concept:C0043491,
umls-concept:C0391871,
umls-concept:C0521390,
umls-concept:C0680255,
umls-concept:C1283071,
umls-concept:C1705294,
umls-concept:C1963578
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pubmed:issue |
10
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pubmed:dateCreated |
2008-9-24
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pubmed:abstractText |
Oxidative stress and zinc release are both known to contribute to neuronal death after hypoglycemia; however, the cause-effect relationships between these events are not established. Here we found, using a rat model of profound hypoglycemia, that the neuronal zinc release and translocation that occur immediately after hypoglycemia are prevented by the nitric oxide synthase inhibitor 7-nitroindazole but not by overexpression of superoxide dismutase-1 (SOD-1). However, overexpression of SOD-1 prevented activation of poly(ADP-ribose) polymerase-1 (PARP-1) and neuronal death, suggesting that zinc release is upstream of superoxide production. Accordingly, zinc-induced superoxide production was blocked in neuronal cultures by the NADPH oxidase inhibitor apocynin and by genetic deficiency in the p47(phox) subunit of NADPH oxidase. A key role for the vesicular zinc pool in this process was suggested by reduced superoxide formation and neuronal death in mice deficient in zinc transporter 3. Together, these findings suggest a series of events in which nitric oxide production triggers vesicular zinc release, which in turn activates NADPH oxidase and PARP-1. This sequence may also occur in other central nervous system disorders in which zinc, nitric oxide, and oxidative stress have been linked.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adprt protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cation Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases,
http://linkedlifedata.com/resource/pubmed/chemical/Slc30a3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxides,
http://linkedlifedata.com/resource/pubmed/chemical/Zinc,
http://linkedlifedata.com/resource/pubmed/chemical/neutrophil cytosolic factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/poly(ADP-ribose)polymerase-1, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/superoxide dismutase 1,
http://linkedlifedata.com/resource/pubmed/chemical/zinc transporter 3, rat
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1559-7016
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
28
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1697-706
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pubmed:meshHeading |
pubmed-meshheading:18545258-Animals,
pubmed-meshheading:18545258-Animals, Genetically Modified,
pubmed-meshheading:18545258-Carrier Proteins,
pubmed-meshheading:18545258-Cation Transport Proteins,
pubmed-meshheading:18545258-Cell Death,
pubmed-meshheading:18545258-Cells, Cultured,
pubmed-meshheading:18545258-Enzyme Inhibitors,
pubmed-meshheading:18545258-Glucose,
pubmed-meshheading:18545258-Hypoglycemia,
pubmed-meshheading:18545258-Membrane Proteins,
pubmed-meshheading:18545258-Mice,
pubmed-meshheading:18545258-Mice, Inbred C57BL,
pubmed-meshheading:18545258-Mice, Mutant Strains,
pubmed-meshheading:18545258-NADPH Oxidase,
pubmed-meshheading:18545258-Neurons,
pubmed-meshheading:18545258-Nitric Oxide,
pubmed-meshheading:18545258-Nitric Oxide Synthase,
pubmed-meshheading:18545258-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:18545258-Rats,
pubmed-meshheading:18545258-Rats, Sprague-Dawley,
pubmed-meshheading:18545258-Superoxide Dismutase,
pubmed-meshheading:18545258-Superoxides,
pubmed-meshheading:18545258-Zinc
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pubmed:year |
2008
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pubmed:articleTitle |
Sequential release of nitric oxide, zinc, and superoxide in hypoglycemic neuronal death.
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pubmed:affiliation |
Department of Neurology, Veterans Affairs Medical Center, University of California, San Francisco, California 94121, USA. sang.suh@ucsf.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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