TNF-α induces protein synthesis through PI3-kinase-Akt/PKB pathway in cardiac myocytes

Eiji Hiraoka, Seinosuke Kawashima, Tomosaburo Takahashi, Yoshiyuki Rikitake, Tadahiro Kitamura, Wataru Ogawa, Mitsuhiro Yokoyama
2001 American Journal of Physiology. Heart and Circulatory Physiology  
TNF-␣ induces protein synthesis through PI3-kinase-Akt/PKB pathway in cardiac myocytes. Am J Physiol Heart Circ Physiol 280: H1861-H1868, 2001.-The activation of phosphatidylinositol (PI) 3-kinase and Akt/protein kinase B (PKB) by tumor necrosis factor (TNF)-␣ and their roles on stimulation of protein synthesis were investigated in cultured neonatal rat cardiac myocytes. Treatment of cells with TNF-␣ resulted in enlargement of cell surface area and stimulation of protein synthesis without
more » ... ing myocyte viability. TNF-␣ 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-␣ was inhibited by a PI3-kinasespecific inhibitor LY-294002 and adenovirus-mediated expression of a dominant negative mutant of PI3-kinase, indicating that TNF-␣ activates Akt/PKB through PI3-kinase activation. Furthermore, TNF-␣-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 PI3kinase-Akt/PKB pathway plays an essential role in protein synthesis induced by TNF-␣ in cardiac myocytes. cardiac hypertrophy; signal transduction; tumor necrosis factor-␣; phosphatidylinositol 3-kinase; protein kinase B Address for reprint requests and other correspondence: S. Kawashima, First
doi:10.1152/ajpheart.2001.280.4.h1861 pmid:11247802 fatcat:idvlqg6nzzccjnzu27vfbpjfi4