García Celina, Nuñez-Anita Rosa Elvira, Thebault Stéphanie, Arredondo Zamarripa David, Jeziorsky Michael C, Martínez de la Escalera Gonzalo, Clapp Carmen
Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM-Juriquilla, 76230, Querétaro, QRO, Mexico.
Endocrine. 2014 Mar;45(2):263-70. doi: 10.1007/s12020-013-9964-4. Epub 2013 May 3.
Endothelial nitric oxide synthase (eNOS)-derived nitric oxide is a major vasorelaxing factor and a mediator of vasopermeability and angiogenesis. Vasoinhibins, a family of antiangiogenic prolactin fragments that include 16 K prolactin, block most eNOS-mediated vascular effects. Vasoinhibins activate protein phosphatase 2A, causing eNOS inactivation through dephosphorylation of eNOS at serine residue 1179 in bovine endothelial cells and thereby blocking vascular permeability. In this study, we examined whether human eNOS phosphorylation at S1177 (analogous to bovine S1179) influences other actions of vasoinhibins. Bovine umbilical vein endothelial cells were stably transfected with human wild-type eNOS (WT) or with phospho-mimetic (S1177D) or non-phosphorylatable (S1177A) eNOS mutants. Vasoinhibins inhibited the increases in eNOS activity, migration, and proliferation following the overexpression of WT eNOS but did not affect these responses in cells expressing S1177D and S1177A eNOS mutants. We conclude that eNOS inhibition by dephosphorylation of S1177 is fundamental for the inhibition of endothelial cell migration and proliferation by vasoinhibins.
内皮型一氧化氮合酶（eNOS）衍生的一氧化氮是一种主要的血管舒张因子，也是血管通透性和血管生成的介质。血管抑制素是一类抗血管生成的催乳素片段家族，包括16K催乳素，可阻断大多数eNOS介导的血管效应。血管抑制素激活蛋白磷酸酶2A，通过使牛内皮细胞中eNOS的丝氨酸残基1179去磷酸化导致eNOS失活，从而阻断血管通透性。在本研究中，我们检测了人eNOS在S1177（类似于牛的S1179）处的磷酸化是否会影响血管抑制素的其他作用。用人类野生型eNOS（WT）或磷酸模拟物（S1177D）或不可磷酸化（S1177A）的eNOS突变体稳定转染牛脐静脉内皮细胞。血管抑制素抑制WT eNOS过表达后eNOS活性、迁移和增殖的增加，但不影响表达S1177D和S1177A eNOS突变体的细胞中的这些反应。我们得出结论，S1177去磷酸化对eNOS的抑制作用是血管抑制素抑制内皮细胞迁移和增殖的基础。
