Department of Physiological Sciences, Center for Environmental and Human Toxicology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA.
Department of Chemistry, Federal University of Lavras (UFLA), Lavras 37200-000, MG, Brazil.
Biomolecules. 2024 Aug 9;14(8):974. doi: 10.3390/biom14080974.
An over-active renin-angiotensin system (RAS) is characterized by elevated angiotensin II (Ang II). While Ang II can promote metabolic and mitochondrial dysfunction in tissues, little is known about its role in the gastrointestinal system (GI). Here, we treated rat primary colonic epithelial cells with Ang II (1-5000 nM) to better define their role in the GI. We hypothesized that Ang II would negatively affect mitochondrial bioenergetics as these organelles express Ang II receptors. Ang II increased cellular ATP production but reduced the mitochondrial membrane potential (MMP) of colonocytes. However, cells maintained mitochondrial oxidative phosphorylation and glycolysis with treatment, reflecting metabolic compensation with impaired MMP. To determine whether lipid dysregulation was evident, untargeted lipidomics were conducted. A total of 1949 lipids were detected in colonocytes spanning 55 distinct (sub)classes. Ang II (1 nM) altered the abundance of some sphingosines [So(d16:1)], ceramides [Cer-AP(t18:0/24:0)], and phosphatidylcholines [OxPC(16:0_20:5(2O)], while 100 nM Ang II altered some triglycerides and phosphatidylserines [PS(19:0_22:1). Ang II did not alter the relative expression of several enzymes in lipid metabolism; however, the expression of pyruvate dehydrogenase kinase 2 () was increased, and can be protective against dyslipidemia. This study is the first to investigate the role of Ang II in colonic epithelial cell metabolism.
肾素-血管紧张素系统（RAS）过度活跃的特征是血管紧张素 II（Ang II）水平升高。虽然 Ang II 可促进组织中的代谢和线粒体功能障碍，但人们对其在胃肠道（GI）中的作用知之甚少。在这里，我们用 Ang II（1-5000 nM）处理大鼠原代结肠上皮细胞，以更好地定义其在 GI 中的作用。我们假设 Ang II 会对线粒体生物能产生负面影响，因为这些细胞器表达 Ang II 受体。Ang II 增加了细胞内的 ATP 产生，但降低了结肠细胞的线粒体膜电位（MMP）。然而，在用 Ang II 处理后，细胞仍能维持线粒体氧化磷酸化和糖酵解，反映出 MMP 受损时的代谢代偿。为了确定脂质失调是否明显，我们进行了非靶向脂质组学分析。在结肠细胞中检测到 1949 种脂质，跨越 55 种不同的（亚）类。Ang II（1 nM）改变了一些神经酰胺 [So(d16:1)]、神经鞘脂 [Cer-AP(t18:0/24:0)] 和磷脂酰胆碱 [OxPC(16:0_20:5(2O)] 的丰度，而 100 nM Ang II 改变了一些甘油三酯和磷脂酰丝氨酸 [PS(19:0_22:1)] 的丰度。Ang II 并未改变脂质代谢中几种酶的相对表达，但丙酮酸脱氢酶激酶 2 () 的表达增加，而 可能对脂代谢紊乱具有保护作用。这项研究首次调查了 Ang II 在结肠上皮细胞代谢中的作用。
