Source:http://linkedlifedata.com/resource/pubmed/id/18980246
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rdf:type | |
lifeskim:mentions |
umls-concept:C0008051,
umls-concept:C0023401,
umls-concept:C0033634,
umls-concept:C0040077,
umls-concept:C0044602,
umls-concept:C0227525,
umls-concept:C0243126,
umls-concept:C0285761,
umls-concept:C0442805,
umls-concept:C1150481,
umls-concept:C1314939,
umls-concept:C1366765,
umls-concept:C1368105,
umls-concept:C1451005,
umls-concept:C1515673,
umls-concept:C1705325
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pubmed:issue |
6
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pubmed:dateCreated |
2008-11-27
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pubmed:abstractText |
This study examined how L-leucine affected DNA synthesis and cell cycle regulatory protein expression in cultured primary chicken hepatocytes. L-Leucine promoted DNA synthesis in a dose- and time-dependent manner, with concomitant increases in cyclin D1 and cyclin E expression. Phospholipase C (PLC) and protein kinase C (PKC) mediated the L-leucine-induced increases in [3H]-thymidine incorporation and cyclin D1/CDK4 and cyclin E/CDK2 expression, as U73122 (a PLC inhibitor) or bisindolylmaleimide I (a PKC blocker) inhibited these effects. L-Leucine also increased PKC phosphorylation and intracellular Ca2+ levels. L-Leucine-mediated increases in [3H]-thymidine incorporation and cyclin/CDK expression were sensitive to LY 294002 (PI3K inhibitor), Akt inhibitor, PD 98059 (MEK inhibitor). It was also observed that L-leucine-induced increases of cyclin/CDK expression were inhibited by PI3K siRNA and ERK siRNA; L-leucine increased extracellular signal-regulated kinases 1/2 (ERK1/2) and Akt phosphorylation levels. Bisindolylmaleimide I attenuated L-leucine-induced phosphorylation of ERK1/2 but did not influence Akt phosphorylation, and PI3K siRNA and LY 294002 inhibited L-leucine-induced ERK1/2 phosphorylation, suggesting some cross-talk between the PKC and ERK1/2 or PI3K/Akt and ERK1/2 pathways. L-Leucine also increased the levels of phosphorylated molecular target of rapamycin (mTOR) and two of its targets, ribosomal protein S6 kinase (p70S6K), and 4E binding protein 1 (4E-BP1); furthermore, rapamycin (an mTOR inhibitor) blocked all of the mitogenic effects of L-leucine. In addition, Akt inhibitor blocked L-leucine-induced mTOR phosphorylation. In conclusion, L-leucine stimulated DNA synthesis and promoted cell cycle progression in primary cultured chicken hepatocytes through PKC, ERK1/2, PI3K/Akt, and mTOR.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Leucine,
http://linkedlifedata.com/resource/pubmed/chemical/MTOR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidine
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1097-4644
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
105
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1410-9
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:18980246-Animals,
pubmed-meshheading:18980246-Cell Cycle,
pubmed-meshheading:18980246-Cell Proliferation,
pubmed-meshheading:18980246-Chickens,
pubmed-meshheading:18980246-Hepatocytes,
pubmed-meshheading:18980246-Leucine,
pubmed-meshheading:18980246-MAP Kinase Signaling System,
pubmed-meshheading:18980246-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:18980246-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:18980246-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:18980246-Protein Kinase C,
pubmed-meshheading:18980246-Protein Kinases,
pubmed-meshheading:18980246-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:18980246-TOR Serine-Threonine Kinases,
pubmed-meshheading:18980246-Thymidine
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pubmed:year |
2008
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pubmed:articleTitle |
L-leucine increases [3H]-thymidine incorporation in chicken hepatocytes: involvement of the PKC, PI3K/Akt, ERK1/2, and mTOR signaling pathways.
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pubmed:affiliation |
Department of Veterinary Physiology, College of Veterinary Medicine, Biotherapy Human Resources Center (BK21), Chonnam National University, Gwangju 500-757, Korea.
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pubmed:publicationType |
Journal Article
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