Zheng Xiangjian, Bollag Wendy B
Institute of Molecular Medicine and Genetics/CB-2803, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912-2630, USA.
Mol Cell Endocrinol. 2003 Aug 29;206(1-2):113-22. doi: 10.1016/s0303-7207(03)00211-9.
In this report we demonstrate that in human adrenocortical carcinoma NCI H295R cells, a model for adrenal glomerulosa cells, PLD was activated both by AngII and protein kinase C (PKC)-activating phorbol 12-myristate 13-acetate (PMA). However, while PMA triggered sustained PLD activation, AngII induced transient PLD activation, in contrast to results in bovine glomerulosa cells in primary culture. Despite the transient effect of AngII on PLD activity, PLD-derived lipid signals were required for maximal AngII-elicited aldosterone secretion. AngII-induced PLD activation was inhibited by PKC inhibitors, but not by tyrosine kinase or calcium/calmodulin-dependent kinase inhibitors or a calmodulin antagonist. Both AngII- and PMA-stimulated PLD activity was enhanced by phosphoinositide 3-kinase (PI3K) inhibitors. Akt, a downstream protein kinase activated by the products of PI3K, was constitutively active in H295R cells, and this activity was blocked by PI3K inhibitors. These results suggested that in H295R adrenocortical carcinoma cells, AngII-induced PLD activation was promoted by PKC and inhibited by the constitutively active PI3K pathway.
在本报告中，我们证明，在肾上腺球状带细胞模型——人肾上腺皮质癌NCI H295R细胞中，磷脂酶D（PLD）可被血管紧张素II（AngII）和激活蛋白激酶C（PKC）的佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）激活。然而，与原代培养的牛球状带细胞的结果相反，PMA触发了持续的PLD激活，而AngII诱导了短暂的PLD激活。尽管AngII对PLD活性有短暂影响，但最大程度的AngII诱导的醛固酮分泌需要PLD衍生的脂质信号。AngII诱导的PLD激活被PKC抑制剂抑制，但不被酪氨酸激酶、钙/钙调蛋白依赖性激酶抑制剂或钙调蛋白拮抗剂抑制。磷脂酰肌醇3 - 激酶（PI3K）抑制剂增强了AngII和PMA刺激的PLD活性。Akt是一种由PI3K产物激活的下游蛋白激酶，在H295R细胞中组成性激活，且该活性被PI3K抑制剂阻断。这些结果表明，在H295R肾上腺皮质癌细胞中，AngII诱导的PLD激活由PKC促进，并被组成性激活的PI3K途径抑制。
