Extracellular taurine induces angiogenesis by activating ERK-, Akt-, and FAK-dependent signal pathways

• Published in: European journal of pharmacology 2012-01, Vol.674 (2-3), p.188-199
• Main Authors: Baek, Yi-Yong, Cho, Dong Hui, Choe, Jongseon, Lee, Hansoo, Jeoung, Dooil, Ha, Kwon-Soo, Won, Moo-Ho, Kwon, Young-Guen, Kim, Young-Myeong
• Format: Article
• Language: English
• Subjects: Akt; Angiogenesis; Cell cycle; Cell Cycle - drug effects; cell movement; Cell Movement - drug effects; cell proliferation; Cell Proliferation - drug effects; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; cyclins; Cyclins - metabolism; endothelial cells; ERK; Extracellular Signal-Regulated MAP Kinases - metabolism; Extracellular Space - drug effects; Extracellular Space - enzymology; Extracellular Space - metabolism; Focal Adhesion Protein-Tyrosine Kinases - metabolism; Gene Expression Regulation - drug effects; Gene Knockdown Techniques; human diseases; Human Umbilical Vein Endothelial Cells - cytology; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - enzymology; Human Umbilical Vein Endothelial Cells - metabolism; Humans; inflammation; mitogen-activated protein kinase; Neovascularization, Physiologic - drug effects; permeability; pharmacology; phosphatidylinositol 3-kinase; Phosphatidylinositol 3-Kinases - metabolism; phosphorylation; Phosphorylation - drug effects; Protein Transport - drug effects; Proto-Oncogene Proteins c-akt - deficiency; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; signal transduction; Signal Transduction - drug effects; src-Family Kinases - metabolism; Taurine; Taurine - pharmacology; Taurine - therapeutic use; Vascular Diseases - drug therapy
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2011.11.022

Taurine, a non essential sulfur-containing amino acid, plays a critical role in cardiovascular functions. We here examined the effect of taurine on angiogenesis and its underlying signal pathway. Taurine treatment increased angiogenesis in vitro and in vivo, which was followed by activation of the phosphatidylinositol 3-kinase (PI3K)/Akt, MEK/ERK, and Src/FAK signaling pathways. Further, taurine promoted endothelial cell cycle progression to the S and G2/M phases by up-regulating the positive cell cycle proteins, particularly cyclins D1 and B, as well as down-regulating the negative cell cycle proteins, p53 and p21WAF1/CIP1, resulting in Rb phosphorylation. This angiogenic event was inhibited by inhibitors of PI3K and MEK. In addition, a PI3K inhibitor blocked the activation of Akt and ERK, while Akt knockdown did not affect taurine-induced ERK activation, indicating that PI3K is an upstream mediator of both MEK and Akt. Taurine-induced endothelial cell migration was suppressed by Src inhibitor, but not by other inhibitors, suggesting that the increase in cell migration is regulated by Src-dependent pathway. Moreover, inhibition of cellular taurine uptake by β-alanine and taurine transporter knockdown promoted taurine-induced cell proliferation, ERK and Akt activation, and in vivo angiogenesis, suggesting that extracellular taurine induces angiogenesis. However, taurine did not induce vascular inflammation and permeability in vitro and in vivo. These data demonstrate that extracellular taurine promotes angiogenesis by Akt- and ERK-dependent cell cycle progression and Src/FAK-mediated cell migration without inducing vascular inflammation, indicating that it is potential use for the treatment of vascular dysfunction-associated human diseases.