Matsunaga Nozomu, Shimazawa Masamitsu, Otsubo Kazumasa, Hara Hideaki
Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
J Pharmacol Sci. 2008 Jan;106(1):128-35. doi: 10.1254/jphs.fp0071166. Epub 2008 Jan 11.
Phosphatidylinositol (PI), a phospholipid in component of cell membranes, is widely distributed in animals, plants, and microorganisms. Here, we examined in vitro whether PI inhibits the angiogenesis induced by vascular endothelial growth factor-A (VEGF-A). PI concentration-relatedly and significantly (at 10 and 30 microg/ml) inhibited VEGF-A-induced tube formation in a co-culture of human umbilical vein endothelial cells (HUVECs) and fibroblasts. PI also inhibited the migration, but not proliferation, induced in HUVECs by VEGF-A. Furthermore, PI at 30 microg/ml inhibited the VEGF-A-induced phosphorylation of serine/threonine protein kinase family protein kinase B (Akt) and p38 mitogen activate kinase (p38MAPK), key molecules in cell migration, but not phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), a key molecule in cell proliferation. These findings indicate that PI inhibits VEGF-induced angiogenesis by inhibiting HUVECs migration and that inhibition of phosphorylated-Akt and -p38MAPK may be involved in the mechanism. Therefore, PI may be expected to prevent some diseases caused by angiogenesis.
磷脂酰肌醇（PI）是细胞膜的一种磷脂成分，广泛分布于动物、植物和微生物中。在此，我们在体外检测了PI是否能抑制血管内皮生长因子-A（VEGF-A）诱导的血管生成。PI以浓度相关的方式显著抑制（在10和30微克/毫升时）人脐静脉内皮细胞（HUVECs）与成纤维细胞共培养体系中VEGF-A诱导的管腔形成。PI还抑制VEGF-A诱导的HUVECs迁移，但不抑制其增殖。此外，30微克/毫升的PI抑制VEGF-A诱导的丝氨酸/苏氨酸蛋白激酶家族蛋白激酶B（Akt）和p38丝裂原活化激酶（p38MAPK）的磷酸化，这两种分子是细胞迁移中的关键分子，但不抑制细胞增殖中的关键分子细胞外信号调节激酶1/2（ERK1/2）的磷酸化。这些发现表明，PI通过抑制HUVECs迁移来抑制VEGF诱导的血管生成，并且对磷酸化Akt和p38MAPK的抑制可能参与了该机制。因此，PI有望预防一些由血管生成引起的疾病。
