Phosphatidylinositol 3-kinase is required for growth factor-induced amino acid uptake by vascular smooth muscle cells
Phosphatidylinositol 3-kinase is required for growth factor-induced amino acid uptake by vascular smooth muscle cells
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DOI：
10.1161/01.atv.19.9.2127
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发表时间：
1999-09-01
影响因子：
8.7
通讯作者：
Shimokado, K
中科院分区：
文献类型：
--
作者：
Higaki, M;Shimokado, K
尽管越来越多的证据表明，磷脂酰肌醇3-激酶（PI3K）是生长因子诱导的细胞摄取氨基酸的常见信号分子，但在相同的条件下，PI3K在不同氨基酸摄取中的作用尚未得到测试。在本研究中，我们研究了PI3K是否介导血小板衍生生长因子（platelet-derived growth factor， PDGF）刺激对大鼠血管平滑肌细胞和其他细胞类型中表达的3种主要氨基酸转运体所摄取的不同氨基酸的摄取，以及PI3K是否介导不同生长因子和血管活性物质刺激的氨基酸摄取。PDGF增加了[H-3]亮氨酸，[H-3]脯氨酸和[H-3]精氨酸的摄取，并呈剂量和时间依赖性。两种不同的PI3K抑制剂wortmannin （100 μ mol/L）和LY294002 （10 μ mol/L）完全抑制PDGF刺激的氨基酸摄取。在PDGF刺激下，同时表达PDCF受体- β和显性阴性PI3K的中国仓鼠卵巢细胞不增加亮氨酸的摄取，而仅表达PDGF受体- β的相同细胞则增加了亮氨酸的摄取。转化生长因子- β，以及胰岛素样生长因子- i和血管紧张素II，增加了血管平滑肌细胞对亮氨酸的摄取。Wortmannin和LY294002抑制了这种增加。我们还发现，转化生长因子- β刺激PI3K活性和PI3K下游信号分子Akt的磷酸化。在Swiss 3T3细胞中观察到PI3K抑制剂对氨基酸摄取的类似作用。我们得出结论，PI3K介导血管平滑肌细胞和其他鳗鱼类型在多种生长因子（包括转化生长因子- β）刺激下对不同氨基酸的摄取，我们的研究结果表明，PI3K可能通过调节氨基酸摄取在血管病理生理中发挥重要作用。
Although accumulating evidence suggests that phosphatidylinositol 3-kinase (PI3K) is a common signaling molecule for growth factor-induced amino acid uptake by the cell, the role of PI3K in the uptake of different amino acids was not tested under the same conditions. In this study, we asked whether PI3K mediates platelet-derived growth factor (PDGF) -stimulated uptake of different amino acids that are taken up through 3 major amino acid transporters expressed in rat vascular smooth muscle cells and other cell types and whether PI3K mediates amino acid uptake stimulated with different growth factors and vasoactive substances. PDGF increased the uptake of [H-3]leucine, [H-3]proline, and [H-3]arginine in a dose- and time-dependent fashion. Two different PI3K inhibitors, wortmannin (100 nmol/L) and LY294002 (10 mu mol/L), completely inhibited the amino acid uptake stimulated by PDGF. Chinese hamster ovary cells expressing both PDCF receptor-beta and a dominant-negative PI3K did not increase their leucine uptake when stimulated with PDGF, whereas the same cells expressing only PDGF receptor-beta did. Transforming growth factor-beta, as well as insulin-like growth factor-I and angiotensin II, increased leucine uptake by vascular smooth muscle cells. Wortmannin and LY294002 inhibited this increase. We also found that transforming growth factor-beta stimulated PI3K activity and the phosphorylation of Akt, a downstream signaling molecule of PI3K. A similar effect of PI3K inhibitors on amino acid uptake was observed in Swiss 3T3 cells. We conclude that PI3K mediates the uptake of different amino acids by vascular smooth muscle cells and other eel types stimulated with a variety of growth factors, including transforming growth factor-beta, Our findings suggest that PI3K may play an important role in vascular pathophysiology by regulating amino acid uptake.