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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2003-11-19
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pubmed:abstractText |
We investigated the effect of diazoxide on neuronal survival in primary cultures of rat cortical neurons against oxygen-glucose deprivation (OGD). Diazoxide pre-treatment induced delayed pre-conditioning and almost entirely attenuated the OGD-induced neuronal death. Diazoxide inhibited succinate dehydrogenase and induced mitochondrial depolarization, free radical production and protein kinase C activation. The putative mitochondrial ATP-sensitive potassium channel blocker 5-hydroxydecanoate abolished the protective effect of diazoxide while the non-selective KATP channel blocker glibenclamide did not. The non-selective KATP channel openers nicorandil and cromakalim did not improve viability. Superoxide dismutase mimetic, M40401, or protein kinase C inhibitor, chelerythrine, prevented the neuroprotective effect of diazoxide. Diazoxide did not increase reduced glutathione and manganese-superoxide dismutase levels but we found significantly higher reduced glutathione levels in diazoxide-pre-conditioned neurons after OGD. In pre-conditioned neurons free radical production was reduced upon glutamate stimulation. The succinate dehydrogenase inhibitor 3-nitropropionic acid also induced pre-conditioning and free radical production in neurons. Here, we provide the first evidence that diazoxide induces delayed pre-conditioning in neurons via acute generation of superoxide anion and activation of protein kinases and subsequent attenuation of oxidant stress following OGD. The succinate dehydrogenase-inhibiting effect of diazoxide is more likely to be involved in this neuroprotection than the opening of mitochondrial ATP-sensitive potassium channels.
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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/3-nitropropionic acid,
http://linkedlifedata.com/resource/pubmed/chemical/5-hydroxydecanoic acid,
http://linkedlifedata.com/resource/pubmed/chemical/Cromakalim,
http://linkedlifedata.com/resource/pubmed/chemical/Decanoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Diazoxide,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Glyburide,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxy Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Nicorandil,
http://linkedlifedata.com/resource/pubmed/chemical/Nitro Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Propionic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Succinate Dehydrogenase,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxides
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0022-3042
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
87
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
969-80
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:14622127-Animals,
pubmed-meshheading:14622127-Cell Death,
pubmed-meshheading:14622127-Cell Hypoxia,
pubmed-meshheading:14622127-Cell Survival,
pubmed-meshheading:14622127-Cells, Cultured,
pubmed-meshheading:14622127-Cerebral Cortex,
pubmed-meshheading:14622127-Cromakalim,
pubmed-meshheading:14622127-Decanoic Acids,
pubmed-meshheading:14622127-Diazoxide,
pubmed-meshheading:14622127-Enzyme Activation,
pubmed-meshheading:14622127-Enzyme Inhibitors,
pubmed-meshheading:14622127-Glucose,
pubmed-meshheading:14622127-Glyburide,
pubmed-meshheading:14622127-Hydroxy Acids,
pubmed-meshheading:14622127-Ischemic Preconditioning,
pubmed-meshheading:14622127-Mitochondria,
pubmed-meshheading:14622127-Neurons,
pubmed-meshheading:14622127-Neuroprotective Agents,
pubmed-meshheading:14622127-Nicorandil,
pubmed-meshheading:14622127-Nitro Compounds,
pubmed-meshheading:14622127-Oxidative Stress,
pubmed-meshheading:14622127-Propionic Acids,
pubmed-meshheading:14622127-Rats,
pubmed-meshheading:14622127-Rats, Wistar,
pubmed-meshheading:14622127-Succinate Dehydrogenase,
pubmed-meshheading:14622127-Superoxides,
pubmed-meshheading:14622127-Time Factors
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pubmed:year |
2003
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pubmed:articleTitle |
Diazoxide induces delayed pre-conditioning in cultured rat cortical neurons.
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pubmed:affiliation |
Department of Physiology and Pharmacology, Wake Forest University, Winston-Salem, North Carolina 27157, USA. bkis@wfubmc.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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