Two intracellular singaling pathways for activation of protein kinase C are involved in oxidized low-density lipoprotein-induced macrophage growth 酸化低密度リポ蛋白質によるマクロファージ増殖には,2つの経路を介するプロテインキナーゼCの活性化が関与する
Two intracellular singaling pathways for activation of protein kinase C are involved in oxidized low-density lipoprotein-induced macrophage growth
Recent studies demonstrated that oxidized LDL(Ox-LDL) induces macrophage growth in vitro. The present study was undertaken to elucidate the intracellular signalingpathways for macrophage growth. Ox-LDL initiated a rapid and transient rise in intracellular free calcium ion and inducedactivation of membrane protein kinase C (PKC). Pertussis toxin completely inhibited the Ox-LDL-induced rise in free calcium ion and significantly inhibited macrophage growth by 50%. Moreover, PKC inhibitors calphostin C and H-7 significantly inhibited Ox-LDL-induced macrophage growth by 80%.On the other hand, phospholipase A2-treated acetylated LDL did not induce a rise in calcium but significantly activated PKC and led to significant macrophage growth that was significantly inhibited by calphostin C by 90%. These results suggest thepresence of two intracellular signaling pathways for activation of PKC, a rise in calcium that was mediated by pertussistoxin-sensitive G protein and the internalization of lysophosphatidylcholinethrough the scavenger receptors. These twopathways may play an important role in Ox-LDL-induced macrophage growth.