title: Phospholipase D activity underlies very-low-density lipoprotein (VLDL)-induced aldosterone production in adrenal glomerulosa cells.
abstract: Aldosterone is the mineralocorticoid responsible for sodium retention, thus increased blood volume and pressure. Excessive production of aldosterone results in high blood pressure as well as renal disease, stroke, and visual loss via both direct effects and effects on blood pressure. Weight gain is often associated with increased blood pressure, but it remains unclear how obesity increases blood pressure. Obese patients typically have higher lipoprotein levels; moreover, some studies have suggested that aldosterone levels are also elevated and represent a link between obesity and hypertension. Very-low-density lipoprotein (VLDL) functions to transport triglycerides from the liver to peripheral tissues. Although previous studies have demonstrated that VLDL can stimulate aldosterone production, the mechanisms underlying this effect are largely unclear. Here we show for the first time that phospholipase D (PLD) is involved in VLDL-induced aldosterone production in both a human adrenocortical cell line (HAC15) and primary cultures of bovine zona glomerulosa cells. Our data also reveal that PLD mediates steroidogenic acute regulatory (StAR) protein and aldosterone synthase (CYP11B2) expression via increasing the phosphorylation (activation) of their regulatory transcription factors. Finally, by using selective PLD inhibitors, our studies suggest that both PLD1 and PLD2 isoforms play an important role in VLDL-induced aldosterone production.
authors: Charlie Norwood VA Medical Center (V.C., W.B.B.), Augusta, Georgia 30904; Department of Physiology (Y.-Y.T., W.E.R., Z.P., V.C., W.B.B.), Medical College of Georgia at Georgia Regents University, Augusta, Georgia 30912; and Department of Pharmacology and Center for Developmental Genetics (M.A.F.), Stony Brook University, Stony Brook, New York 11794.
authors: Ying-Ying
authors: YY
authors: Tsai
authors: William E
authors: WE
authors: Rainey
authors: Zhi-qiang
authors: ZQ
authors: Pan
authors: Michael A
authors: MA
authors: Frohman
authors: Vivek
authors: V
authors: Choudhary
authors: Wendy B
authors: WB
authors: Bollag
mesh_terms: D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism*; D015384:Zona Glomerulosa / Q000201:enzymology* / Q000378:metabolism
chemical_list: D008079:Lipoproteins, VLDL; D000450:Aldosterone; C105606:phospholipase D2; D010739:Phospholipase D; C106801:phospholipase D1