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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-8-9
pubmed:abstractText
We previously demonstrated that the neuropeptide cocaine- and amphetamine-regulated transcript (CART) is protective against focal cerebral ischemia in vivo and against neuronal cell death in culture induced by oxygen-glucose deprivation (OGD). The mechanism of neuroprotection by CART is unknown, in part due to lack of knowledge regarding its putative receptor. Using a yeast two-hybrid system with CART's carboxy-terminal to screen a mouse brain cDNA library, we uncovered a potential direct interaction between CART and subunit B of the mitochondrial enzyme succinate dehydrogenase (SDHB). We confirmed CART/SDHB binding using in vitro pull-down assay, and tested the effects of CART peptide on SDH activity, Complex II (CII) activity and ATP production in primary cultured cortical neurons under basal conditions and after OGD. At concentrations between 0.2 and 4 nM, CART significantly increased SDH function, CII activity and ATP generation in purified mitochondria and intact neurons under baseline conditions. Furthermore, pretreatment with CART enhanced mitochondrial mechanisms of neuronal survival and prevented the decline in SDH and CII activities and ATP production after OGD. The findings suggest that CART's neuroprotective mechanism of action may be linked to preservation of mitochondrial function and prevention of energy failure after ischemia-reperfusion injury.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-10508238, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-10567018, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-10900261, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-11522684, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-11567037, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-11677274, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-11711504, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-11850744, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-12082502, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-12374491, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-12560550, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-12588509, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-12665464, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-12914986, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-12933358, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-12958177, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-14622127, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-14759497, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-15183071, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-15908120, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-16024766, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-16146347, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-16179521, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-16309793, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-16443761, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-16713658, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-16762453, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-16822586, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-16842741, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-16971488, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-17025271, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-17035515, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-17083736, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-17178711, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-2547163, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-7891182, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-9192388, http://linkedlifedata.com/resource/pubmed/commentcorrection/17634068-9590691
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0953-816X
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
624-32
pubmed:dateRevised
2011-4-11
pubmed:meshHeading
pubmed-meshheading:17634068-Adenosine Triphosphate, pubmed-meshheading:17634068-Animals, pubmed-meshheading:17634068-Cells, Cultured, pubmed-meshheading:17634068-Cerebral Cortex, pubmed-meshheading:17634068-Cytoprotection, pubmed-meshheading:17634068-Electron Transport Complex II, pubmed-meshheading:17634068-Energy Metabolism, pubmed-meshheading:17634068-Hypoxia-Ischemia, Brain, pubmed-meshheading:17634068-Iron-Sulfur Proteins, pubmed-meshheading:17634068-Mitochondria, pubmed-meshheading:17634068-Nerve Tissue Proteins, pubmed-meshheading:17634068-Neurons, pubmed-meshheading:17634068-Neuroprotective Agents, pubmed-meshheading:17634068-Protein Binding, pubmed-meshheading:17634068-Rats, pubmed-meshheading:17634068-Reperfusion Injury, pubmed-meshheading:17634068-Succinate Dehydrogenase, pubmed-meshheading:17634068-Two-Hybrid System Techniques
pubmed:year
2007
pubmed:articleTitle
Mitochondrial mechanism of neuroprotection by CART.
pubmed:affiliation
Department of Public Health & Preventive Medicine, Oregon Health & Science University, Portland, OR 97239-3098, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't
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