Fas Signaling Induces Akt Activation and Upregulation of Endothelial Nitric Oxide Synthase Expression
Fas Signaling Induces Akt Activation and Upregulation of Endothelial Nitric Oxide Synthase Expression
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DOI：
10.1161/01.hyp.0000120124.27641.03
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发表时间：
2004-04
期刊：
影响因子：
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通讯作者：
Y. Takemura;K. Fukuo;O. Yasuda;Takahito Inoue;N. Inomata;T. Yokoi;H. Kawamoto;T. Suhara;T. Ogihara
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文献类型：
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作者：
Y. Takemura;K. Fukuo;O. Yasuda;Takahito Inoue;N. Inomata;T. Yokoi;H. Kawamoto;T. Suhara;T. Ogihara
摘要-越来越多的证据表明，Fas，死亡受体，介导的阿尔茨海默病无关的生物学效应。在这里，我们报告，Fas与Fas配体参与诱导Akt的激活和上调内皮型一氧化氮合酶的表达，而不诱导细胞凋亡。在磷脂酰肌醇3-激酶抑制剂渥曼青霉素，Fas配体的存在下，然而，诱导细胞凋亡，而不是上调内皮型一氧化氮合酶的表达。在体内，与野生型小鼠相比，细胞表面Fas表达降低的突变小鼠（lpr小鼠）的收缩压略高。此外，慢性抑制一氧化氮合成的NG-硝基-L-精氨酸诱导的野生型小鼠的血压水平的逐步增加，而没有进一步增加的血压水平在lpr小鼠中观察到。此外，与野生型小鼠相比，乙酰胆碱引起lpr小鼠条的内皮依赖性舒张作用较小，尽管苯丙氨酸的血管收缩效力在两组之间没有差异。这些结果表明，Fas信号可能通过调节内皮细胞一氧化氮合酶的表达，Akt信号依赖的方式在调节内皮功能和血压的作用。
Abstract—A growing body of evidence has shown that Fas, a death receptor, mediates apoptosis-unrelated biological effects. Here, we report that Fas engagement with Fas ligand induced activation of Akt and upregulation of endothelial nitric oxide synthase expression without induction of apoptosis. In the presence of the phosphatidylinositol 3-kinase inhibitor wortmannin, Fas ligand, however, induced apoptosis instead of upregulation of endothelial nitric oxide synthase expression. In vivo, systolic blood pressure was slightly higher in mutant mice with decreased cell surface Fas expression (lpr mice) compared with wild-type mice. In addition, chronic inhibition of nitric oxide synthesis by NG-nitro-l-arginine induced a progressive increase in the levels of blood pressure in wild-type mice, whereas no further increase in the levels of blood pressure was observed in lpr mice. Furthermore, acetylcholine caused a lesser endothelium-dependent relaxation of the strips from lpr mice compared with wild-type mice, although the vasoconstrictor potency of phenylephrine was not different between the two groups. These findings indicate that Fas signaling may have a role in the regulation of endothelial function and blood pressure through modulating endothelial nitric oxide synthase expression in the Akt signal-dependent manner.