Mamedova Esmira, Árting Lív Bech, Rekling Jens C
Department of Neuroscience, University of Copenhagen, Panum - 24.4, Blegdamsvej 3, DK-2200, Copenhagen N, Denmark.
Biochem Biophys Rep. 2022 May 31;31:101288. doi: 10.1016/j.bbrep.2022.101288. eCollection 2022 Sep.
Bile acids (BAs) play an important role in the digestion of dietary fats and act as signaling molecules. However, due to their solubilizing properties, high concentrations in the gut may negatively affect gut epithelium and possibly afferent fibers innervating the gastrointestinal tract (GI). To determine the effect of BAs on intracellular Ca and membrane permeabilization we tested a range of concentrations of two BAs on vagal nodose ganglion (NG) neurons, Chinese Hamster Ovary (CHO), and PC12 cell lines. NG explants from mice were drop-transduced with the genetically encoded Ca indicator AAV9-Syn-jGCaMP7s and used to measure Ca changes upon application of deoxycholic acid (DCA) and taurocholic acid (TCA). We found that both BAs induced a Ca increase in NG neurons in a dose-dependent manner. The DCA-induced Ca increase was dependent on intracellular Ca stores. NG explants, with an intact peripheral part of the vagus nerve, showed excitation of NG neurons in nerve field recordings upon exposure to DCA. The viability of NG neurons at different BA concentrations was determined, and compared to CHO and PC12 cells lines using propidium iodide labeling, showing threshold concentrations of BA-induced cell death at 400-500 μM. These observations suggest that BAs act as Ca-inducing signaling molecules in vagal sensory neurons at low concentrations, but induce cell death at higher concentrations, which may occur during inflammatory bowel diseases.
胆汁酸（BAs）在膳食脂肪消化中起重要作用，并作为信号分子发挥作用。然而，由于其溶解特性，肠道中高浓度的胆汁酸可能对肠道上皮产生负面影响，并可能影响支配胃肠道（GI）的传入纤维。为了确定胆汁酸对细胞内钙和膜通透性的影响，我们在迷走神经节（NG）神经元、中国仓鼠卵巢（CHO）细胞系和PC12细胞系上测试了一系列浓度的两种胆汁酸。从小鼠获取的NG外植体用基因编码的钙指示剂AAV9-Syn-jGCaMP7s进行滴注转导，并用于测量在应用脱氧胆酸（DCA）和牛磺胆酸（TCA）时的钙变化。我们发现两种胆汁酸均以剂量依赖性方式诱导NG神经元中的钙增加。DCA诱导的钙增加依赖于细胞内钙库。具有完整迷走神经外周部分的NG外植体在暴露于DCA时，在神经场记录中显示出NG神经元的兴奋。使用碘化丙啶标记确定了不同胆汁酸浓度下NG神经元的活力，并与CHO和PC12细胞系进行比较，结果显示胆汁酸诱导细胞死亡的阈值浓度为400 - 500μM。这些观察结果表明，低浓度时胆汁酸在迷走感觉神经元中作为钙诱导信号分子起作用，但在高浓度时诱导细胞死亡，这可能在炎症性肠病期间发生。
