title: VLDL-activated cell signaling pathways that stimulate adrenal cell aldosterone production.
abstract: Aldosterone plays an important role in regulating ion and fluid homeostasis and thus blood pressure, and hyperaldosteronism results in hypertension. Hypertension is also observed with obesity, which is associated with additional health risks, including cardiovascular disease. Obese individuals have high serum levels of very low-density lipoprotein (VLDL), which has been shown to stimulate aldosterone production; however, the mechanisms underlying VLDL-induced aldosterone production are still unclear. Here we demonstrate in human adrenocortical carcinoma (HAC15) cells that submaximal concentrations of angiotensin II and VLDL stimulate aldosterone production in an additive fashion, suggesting the possibility of common mechanisms of action. We show using inhibitors that VLDL-induced aldosterone production is mediated by the PLC/IP3/PKC signaling pathway. Our results suggest that PKC is upstream of the extracellular signal-regulated kinase (ERK) activation previously observed with VLDL. An understanding of the mechanisms mediating VLDL-induced aldosterone production may provide insights into therapies to treat obesity-associated hypertension.
authors.affiliation: Department of Physiology, Medical College of Georgia at Augusta University, 1120 15th Street, Augusta, GA, 30912, United States.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Tsai
authors.affiliation: Department of Physiology, Medical College of Georgia at Augusta University, 1120 15th Street, Augusta, GA, 30912, United States.
authors.forename: William E
authors.initials: WE
authors.lastname: Rainey
authors.affiliation: Department of Biostatistics and Epidemiology, Medical College of Georgia at Augusta University, 1120 15th Street, Augusta, GA, 30912, United States.
authors.forename: Maribeth H
authors.initials: MH
authors.lastname: Johnson
authors.affiliation: Charlie Norwood VA Medical Center, One Freedom Way, Augusta, GA, 30904, United States; Department of Physiology, Medical College of Georgia at Augusta University, 1120 15th Street, Augusta, GA, 30912, United States. Electronic address: wbollag@augusta.edu.
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Bollag
mesh_terms: D018268:Adrenocortical Carcinoma / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D008079:Lipoproteins, VLDL; D000804:Angiotensin II; D000450:Aldosterone; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Adrenal cortex; Aldosterone; Obesity; Phospholipase C; Protein kinase C; VLDL; Zona glomerulosa