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rdf:type |
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lifeskim:mentions |
umls-concept:C0010749,
umls-concept:C0021289,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0044602,
umls-concept:C0162638,
umls-concept:C0242184,
umls-concept:C0285761,
umls-concept:C0392756,
umls-concept:C0442805,
umls-concept:C1150481,
umls-concept:C1368105,
umls-concept:C1383501,
umls-concept:C1451005,
umls-concept:C1519355,
umls-concept:C1705325,
umls-concept:C1882598
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pubmed:issue |
1
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pubmed:dateCreated |
2004-4-19
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pubmed:abstractText |
Acute hypoxia can deplete ATP and induce mitochondrial release of cytochrome c (cyt c) to initiate or enhance apoptosis, a process delayed or overcome with sufficient ATP and phosphorylation (activation) of survival factors such as Akt (also known as Protein Kinase B). We used an ex vivo brain slice model to investigate associations between levels of phosphorylated Akt (phospho-Akt) and the extent of intrinsic pathway apoptosis. Additionally, phosphorylation (inactivation) was measured of Bad, which is known to promote mitochondrial release of cyt c. Superfused cerebrocortical slices from 7-day-old rats underwent 30-min hypoxia followed by 4-h reoxygenation. At end-hypoxia, Western blots of phospho-Akt became nearly undetectable but returned immediately during recovery and increased thereafter. Cyt c behaved oppositely, being greatest at end-hypoxia and continually decreasing during recovery. Continuous inhibition of phosphoinositide 3-kinase (PI3K) with 10 microM LY294002 suppressed post-hypoxic phospho-Akt levels, prevented post-hypoxic cytosolic cyt c reductions, and increased apoptosis evaluated by TUNEL staining and DNA fragmentation. Western blot analysis demonstrated enhanced Bad translocation from cytosol to mitochondria in the LY294002 group. Phospho-Akt/phospho-Bad double staining revealed colocalization. Parallel (31)P NMR studies showed no effects on NTP production by LY294002. The data support prominent roles for Bad phosphorylation in phospho-Akt's reduction of cyt c apoptosis, and possible apoptotic roles at mitochondrial targets of Bad.
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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/2-(4-morpholinyl)-8-phenyl-4H-1-benz...,
http://linkedlifedata.com/resource/pubmed/chemical/Akt1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Bad protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Chaperonin 60,
http://linkedlifedata.com/resource/pubmed/chemical/Chromones,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochromes c,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphorus Isotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-Associated Death Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0169-328X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
29
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pubmed:volume |
124
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
51-61
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pubmed:dateRevised |
2011-8-1
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pubmed:meshHeading |
pubmed-meshheading:15093685-Animals,
pubmed-meshheading:15093685-Animals, Newborn,
pubmed-meshheading:15093685-Anoxia,
pubmed-meshheading:15093685-Apoptosis,
pubmed-meshheading:15093685-Brain,
pubmed-meshheading:15093685-Carrier Proteins,
pubmed-meshheading:15093685-Chaperonin 60,
pubmed-meshheading:15093685-Chromones,
pubmed-meshheading:15093685-Cytochromes c,
pubmed-meshheading:15093685-Cytosol,
pubmed-meshheading:15093685-DNA Fragmentation,
pubmed-meshheading:15093685-Enzyme Inhibitors,
pubmed-meshheading:15093685-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:15093685-Fluorescent Antibody Technique,
pubmed-meshheading:15093685-In Situ Nick-End Labeling,
pubmed-meshheading:15093685-Magnetic Resonance Imaging,
pubmed-meshheading:15093685-Mitochondria,
pubmed-meshheading:15093685-Morpholines,
pubmed-meshheading:15093685-Neural Inhibition,
pubmed-meshheading:15093685-Neurons,
pubmed-meshheading:15093685-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:15093685-Phosphorus Isotopes,
pubmed-meshheading:15093685-Phosphorylation,
pubmed-meshheading:15093685-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15093685-Proto-Oncogene Proteins,
pubmed-meshheading:15093685-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15093685-Rats,
pubmed-meshheading:15093685-Rats, Sprague-Dawley,
pubmed-meshheading:15093685-Serine,
pubmed-meshheading:15093685-Staining and Labeling,
pubmed-meshheading:15093685-Time Factors,
pubmed-meshheading:15093685-bcl-Associated Death Protein
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pubmed:year |
2004
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pubmed:articleTitle |
PI3K inhibition in neonatal rat brain slices during and after hypoxia reduces phospho-Akt and increases cytosolic cytochrome c and apoptosis.
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pubmed:affiliation |
Department of Anesthesia, University of California, San Francisco, 521 Parnassus Avenue, Room C455, San Francisco, CA 94143-0648, USA.
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pubmed:publicationType |
Journal Article
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