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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Lee, Min Young; Jo, Sung Duk; Lee, Jang-Hern; Han, Ho Jae
Issue Date
J Cell Biochem 105(6): 1410–1419
L-leucine[3H]-thymidine incorporationChicken hepatocytes
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.
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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