Tsai Ying-Ying, Rainey William E, Johnson Maribeth H, Bollag Wendy B
Department of Physiology, Medical College of Georgia at Augusta University, 1120 15th Street, Augusta, GA, 30912, United States.
Department of Biostatistics and Epidemiology, Medical College of Georgia at Augusta University, 1120 15th Street, Augusta, GA, 30912, United States.
Mol Cell Endocrinol. 2016 Sep 15;433:138-46. doi: 10.1016/j.mce.2016.05.018. Epub 2016 May 21.
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.
醛固酮在调节离子和体液平衡进而调节血压方面发挥着重要作用，而醛固酮增多症会导致高血压。肥胖也会引发高血压，且肥胖还与包括心血管疾病在内的其他健康风险相关。肥胖个体的血清极低密度脂蛋白（VLDL）水平较高，已证实其可刺激醛固酮的产生；然而，VLDL诱导醛固酮产生的潜在机制仍不清楚。在此，我们在人肾上腺皮质癌细胞（HAC15）中证明，亚最大浓度的血管紧张素II和VLDL以相加的方式刺激醛固酮的产生，提示可能存在共同的作用机制。我们使用抑制剂表明，VLDL诱导的醛固酮产生是由PLC/IP3/PKC信号通路介导的。我们的结果表明，蛋白激酶C（PKC）位于先前观察到的由VLDL激活的细胞外信号调节激酶（ERK）的上游。对介导VLDL诱导醛固酮产生机制的了解可能为治疗肥胖相关高血压的疗法提供思路。
