Hiraoka E, Kawashima S, Takahashi T, Rikitake Y, Kitamura T, Ogawa W, Yokoyama M
First Department of Internal Medicine, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Am J Physiol Heart Circ Physiol. 2001 Apr;280(4):H1861-8. doi: 10.1152/ajpheart.2001.280.4.H1861.
The activation of phosphatidylinositol (PI) 3-kinase and Akt/protein kinase B (PKB) by tumor necrosis factor (TNF)-alpha and their roles on stimulation of protein synthesis were investigated in cultured neonatal rat cardiac myocytes. Treatment of cells with TNF-alpha resulted in enlargement of cell surface area and stimulation of protein synthesis without affecting myocyte viability. TNF-alpha induced marked activation of PI3-kinase and Akt/PKB, and the activation of PI3-kinase and Akt/PKB was rapid (maximal at 10 and 15 min, respectively) and concentration dependent. Akt/PKB activation by TNF-alpha was inhibited by a PI3-kinase-specific inhibitor LY-294002 and adenovirus-mediated expression of a dominant negative mutant of PI3-kinase, indicating that TNF-alpha activates Akt/PKB through PI3-kinase activation. Furthermore, TNF-alpha-induced protein synthesis was inhibited by pretreatment with LY-294002 and expression of a dominant negative mutant of PI3-kinase or Akt/PKB. These results indicate that activation of the PI3-kinase-Akt/PKB pathway plays an essential role in protein synthesis induced by TNF-alpha in cardiac myocytes.
在培养的新生大鼠心肌细胞中，研究了肿瘤坏死因子（TNF）-α对磷脂酰肌醇（PI）3激酶和Akt/蛋白激酶B（PKB）的激活作用及其对蛋白质合成刺激的作用。用TNF-α处理细胞导致细胞表面积增大和蛋白质合成受到刺激，而不影响心肌细胞活力。TNF-α诱导PI3激酶和Akt/PKB显著激活，且PI3激酶和Akt/PKB的激活迅速（分别在10分钟和15分钟时达到最大值）且呈浓度依赖性。PI3激酶特异性抑制剂LY-294002和腺病毒介导的PI3激酶显性负突变体的表达可抑制TNF-α对Akt/PKB的激活，表明TNF-α通过激活PI3激酶来激活Akt/PKB。此外，LY-294002预处理以及PI3激酶或Akt/PKB显性负突变体的表达可抑制TNF-α诱导的蛋白质合成。这些结果表明，PI3激酶-Akt/PKB途径的激活在TNF-α诱导的心肌细胞蛋白质合成中起重要作用。
