De Souza Aloa Machado, de Carvalho Thaís Louise Gurjão, Lara Lucienne da Silva, Gomes-Quintana Elaine, Lopes Anibal Gil, Caruso-Neves Celso
Instituto Federal de Educação Ciência e Tecnologia do Rio de Janeiro, Lúcio Tavares 1045, 26350-060 Centro, Nilópolis, Rio de Janeiro, Brazil.
Biochim Biophys Acta. 2010 Mar;1798(3):354-9. doi: 10.1016/j.bbamem.2009.11.014. Epub 2009 Dec 1.
Angiotensin II (Ang II) stimulates the proximal tubule Na(+)-ATPase through the AT(1) receptor/phosphoinositide phospholipase Cbeta (PI-PLCbeta)/protein kinase C (PKC) pathway. However, this pathway alone does not explain the sustained effect of Ang II on Na(+)-ATPase activity for 30 min. The aim of the present work was to elucidate the molecular mechanisms involved in the sustained effect of Ang II on Na(+)-ATPase activity. Ang II induced fast and correlated activation of Na(+)-ATPase and PKC activities with the maximal effect (115%) observed at 1 min and sustained for 30 min, indicating a pivotal role of PKC in the modulation of Na(+)-ATPase by Ang II. We observed that the sustained activation of PKC by Ang II depended on the sequential activation of phospholipase D and Ca(2+)-insensitive phospholipase A(2), forming phosphatidic acid and lysophosphatidic acid, respectively. The results indicate that PKC could be the final target and an integrator molecule of different signaling pathways triggered by Ang II, which could explain the sustained activation of Na(+)-ATPase by Ang II.
血管紧张素II（Ang II）通过AT(1)受体/磷酸肌醇磷脂酶Cβ（PI-PLCβ）/蛋白激酶C（PKC）途径刺激近端小管Na(+)-ATP酶。然而，仅这一途径并不能解释Ang II对Na(+)-ATP酶活性长达30分钟的持续作用。本研究的目的是阐明Ang II对Na(+)-ATP酶活性持续作用所涉及的分子机制。Ang II诱导Na(+)-ATP酶和PKC活性快速且相关的激活，在1分钟时观察到最大效应（115%）并持续30分钟，表明PKC在Ang II调节Na(+)-ATP酶中起关键作用。我们观察到Ang II对PKC的持续激活依赖于磷脂酶D和钙不敏感磷脂酶A(2)的顺序激活，分别形成磷脂酸和溶血磷脂酸。结果表明，PKC可能是Ang II触发的不同信号通路的最终靶点和整合分子，这可以解释Ang II对Na(+)-ATP酶的持续激活。
