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L-leucine increases [3H]-thymidine incorporation in chicken hepatocytes: Involvement of the PKC, PI3K/Akt, ERK1/2, and mTOR signaling pathways
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Min Young | - |
dc.contributor.author | Jo, Sung Duk | - |
dc.contributor.author | Lee, Jang-Hern | - |
dc.contributor.author | Han, Ho Jae | - |
dc.date.accessioned | 2009-08-31T23:33:54Z | - |
dc.date.available | 2009-08-31T23:33:54Z | - |
dc.date.issued | 2008-11-03 | - |
dc.identifier.citation | J Cell Biochem 105(6): 1410–1419 | en |
dc.identifier.issn | 0730-2312 | - |
dc.identifier.uri | https://hdl.handle.net/10371/8288 | - |
dc.description.abstract | 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. LLeucine also increased PKC phosphorylation and intracellular Ca2þ 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 Lleucine- induced increases of cyclin/CDK expression were inhibited by PI3K siRNA and ERK siRNA; L-leucine increased extracellular signalregulated 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. | en |
dc.language.iso | en | en |
dc.publisher | Wiley-Blackwell | en |
dc.subject | L-leucine | en |
dc.subject | [3H]-thymidine incorporation | en |
dc.subject | Chicken hepatocytes | en |
dc.title | L-leucine increases [3H]-thymidine incorporation in chicken hepatocytes: Involvement of the PKC, PI3K/Akt, ERK1/2, and mTOR signaling pathways | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 이민영 | - |
dc.contributor.AlternativeAuthor | 조성덕 | - |
dc.contributor.AlternativeAuthor | 이장헌 | - |
dc.contributor.AlternativeAuthor | 한호재 | - |
dc.identifier.doi | 10.1002/jcb.21959 | - |
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