A Possible Role for Phospholipase D2 in Aldosterone Production In Vivo

Presentation Number: SUN 533
Date of Presentation: April 2nd, 2017

Wendy B Bollag*1, Vivek Choudhary2, Lawrence Ogweno Olala2 and Ismail Kaddour-Djebbar1
1Charlie Norwood VA Medical Center, Augusta, GA, 2Augusta University, Augusta, GA


Aldosterone is a mineralocorticoid produced by the adrenal gland and responsible for sodium retention by the kidney. Although this hormone is important for physiological regulation of blood volume and thus pressure, under conditions of a high-salt Western diet, excess aldosterone can result in hypertension and exacerbate congestive heart failure, renal disease and other pathologic disorders. We have previously shown that the lipid-metabolizing enzyme phospholipase D (PLD), and in particular PLD2, mediates aldosterone production in vitro in response to angiotensin II (AngII), the primary physiological regulator of aldosterone secretion. To determine the role of PLD2 in vivo, we compared the adrenal expression of CYP11B2, the gene encoding aldosterone synthase, in PLD2 knockout mice versus wild-type mice of the same strain background. PLD2 knockout and C57BL/6 wild-type mice were fed for one week with a normal or sodium-deficient diet. Adrenal glands were harvested, RNA isolated and CYP11B2 mRNA levels determined by quantitative RT-PCR. In approximately 27-week-old male mice, there was no difference in expression on the normal-salt (1% NaCl) diet. However, a sodium-deficient diet significantly increased CYP11B2 expression, and this increase was blunted in the PLD2 knockout mice by about 30% (n=3-5 per group). Similar results were observed in 11-week-old female mice, in which PLD2 gene knockout resulted in an increase in CYP11B2 expression in mice fed a sodium-deficient diet that was only about 60% of that observed in wild-type mice (n=5-6 per group). However, in about 19-week-old male mice there was no significant difference in the response to low-salt diet in wild-type versus PLD2 knockout mice (n=5-6 per group). Therefore, although PLD may play a role in aldosterone production in vivo, its exact contribution may depend on age and/or sex, and additional studies are obviously warranted. In addition, the mechanism by which PLD acts to regulate aldosterone production is unclear as PLD can produce multiple lipid signaling molecules. Diacylglycerol, a lipid signal known to activate protein kinase C and other enzymes, can be produced by the combined action of PLD and lipins. Lipin1, 2 and 3 have been found to be expressed in the H295R human adrenocarcinoma cell line; we examined the effect of AngII on lipin1 expression in the HAC15 cell line, an H295R clone. A 60-minute treatment with 10 nM AngII significantly increased lipin1 mRNA levels by about 7.6- ± 2.7-fold over the control. These results suggest the possibility that diacylglycerol is the lipid signal produced by PLD (in collaboration with lipin) to mediate, at least in part, the enzyme’s ability to promote aldosterone production.


Nothing to Disclose: WBB, VC, LOO, IK