5(S)-hydroxyeicosatetraenoic acid stimulates DNA synthesis in human microvascular endothelial cells via activation of Jak/STAT and phosphatidylinositol 3-kinase/Akt signaling, leading to induction of expression of basic fibroblast growth factor 2.
作者： Zhao-Zhu Zeng , Chandrahasa R. Yellaturu , Indira Neeli , Gadiparthi N. Rao
关键词:
摘要: To understand the role of eicosanoids in angiogenesis, we have studied effect lipoxygenase metabolites arachidonic acid on human microvascular endothelial cell (HMVEC) DNA synthesis. Among various tested, 5(S)-hydroxyeicosatetraenoic (5(S)-HETE) induced synthesis HMVEC. 5(S)-HETE also stimulated Jak-2, STAT-1, and STAT-3 tyrosine phosphorylation STAT-3-DNA binding activity. Tyrphostin AG490, a specific inhibitor significantly reduced activity by 5(S)-HETE. In addition, phosphatidylinositol 3-kinase (PI3-kinase) its downstream targets Akt, p70S6K, 4E-BP1 their effector molecules ribosomal protein S6 eIF4E. LY294002 rapamycin, potent inhibitors PI3-kinase mTOR, respectively, blocked Interestingly, AG490 attenuated 5(S)-HETE-induced S6, 4E-BP1, expression basic fibroblast growth factor 2 (bFGF-2) Jak-2- PI3-kinase-dependent manner. neutralizing anti-bFGF-2 antibody completely Together these results suggest that stimulates HMVEC via induction bFGF-2. These findings reveal cross-talk between Jak-2 response to
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