Department of Physiology, Georgia Health Sciences University (formerly the Medical College of Georgia), 1120 15th Street, Augusta, GA 30912, United States.
Mol Cell Endocrinol. 2013 Feb 5;366(1):31-7. doi: 10.1016/j.mce.2012.11.008. Epub 2012 Nov 20.
The mineralocorticoid aldosterone plays an important role in regulating blood pressure, with excess causing hypertension and exacerbating cardiovascular disease. Previous studies have indicated a role for both phospholipase D (PLD) and protein kinase D (PKD) in angiotensin II (AngII)-regulated aldosterone production in adrenal glomerulosa cells. Therefore, the relationship between AngII-activated PLD and PKD was determined in two glomerulosa cell models, primary bovine zona glomerulosa (ZG) and HAC15 human adrenocortical carcinoma cells, using two inhibitors, 1-butanol and the reported PLD inhibitor, fluoro-2-indolyl des-chlorohalopemide (FIPI). FIPI was first confirmed to decrease PLD activation in response to AngII in the two glomerulosa cell models. Subsequently, it was shown that both 1-butanol and FIPI inhibited AngII-elicited PKD activation and aldosterone production. These results indicate that PKD is downstream of PLD and suggest that PKD is one of the mechanisms through which PLD promotes aldosterone production in response to AngII in adrenal glomerulosa cells.
醛固酮作为一种盐皮质激素，在调节血压方面发挥着重要作用，其过量可导致高血压，并使心血管疾病恶化。先前的研究表明，磷脂酶 D (PLD) 和蛋白激酶 D (PKD) 在血管紧张素 II (AngII) 调节肾上腺球状带细胞醛固酮生成中均发挥作用。因此，本研究在两种球状带细胞模型，即原代牛肾上腺球状带 (ZG) 和 HAC15 人肾上腺皮质癌细胞中，使用两种抑制剂，1-丁醇和报道的 PLD 抑制剂氟-2-吲哚基去氯卤派啶 (FIPI)，确定了 AngII 激活的 PLD 和 PKD 之间的关系。首先，FIPI 被证实可降低两种球状带细胞模型中 AngII 诱导的 PLD 激活。随后，结果表明 1-丁醇和 FIPI 均可抑制 AngII 诱导的 PKD 激活和醛固酮生成。这些结果表明 PKD 位于 PLD 的下游，提示 PKD 是 PLD 促进 AngII 诱导的肾上腺球状带细胞醛固酮生成的机制之一。
