Orth H Noreen, Pirkwieser Philip, Benthin Julia, Koehler Melanie, Sterneder Sonja, Parlar Etkin, Schaudy Erika, Lietard Jory, Michel Timm, Boger Valerie, Dunkel Andreas, Somoza Mark M, Somoza Veronika
Graduate School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.
Leibniz-Institute for Food Systems Biology, Technical University of Munich, 85354 Freising, Germany.
Int J Mol Sci. 2025 Jun 23;26(13):6017. doi: 10.3390/ijms26136017.
The essential micronutrient zinc is known to inhibit gastric acid secretion (GAS), where its homeostasis is strictly regulated. We hypothesized that the gastric bitter taste receptors, TAS2Rs, regulate the following: (i) zinc-modulated proton secretory activity (PSA) as a key mechanism of GAS and (ii) zinc homeostasis in immortalized parietal cells. To confirm this hypothesis, human gastric tumor cells (HGT-1) were exposed to 100-1000 µM of zinc salts for 30 min in order to quantitate their TAS2R-dependent PSA and intracellular zinc concentration using a fluorescence-based pH sensor and ICP-MS, respectively. Thereby, we identified TAS2R43 as a key player in parietal cell PSA and zinc homeostasis, with both conclusions being verified by a CRISPR-Cas9 knockout approach. Moreover, by regulating the zinc importer protein ZIP14, TAS2R43 proved to perform a protective role against excessive zinc accumulation in immortalized parietal cells.
必需微量元素锌已知可抑制胃酸分泌（GAS），其体内平衡受到严格调节。我们假设胃苦味受体TAS2Rs可调节以下方面：（i）锌调节的质子分泌活性（PSA）作为胃酸分泌的关键机制，以及（ii）永生化壁细胞中的锌稳态。为了证实这一假设，将人胃肿瘤细胞（HGT-1）暴露于100 - 1000 µM的锌盐中30分钟，以便分别使用基于荧光的pH传感器和电感耦合等离子体质谱法（ICP-MS）来定量其依赖TAS2R的PSA和细胞内锌浓度。由此，我们确定TAS2R43是壁细胞PSA和锌稳态的关键参与者，这两个结论均通过CRISPR-Cas9基因敲除方法得到验证。此外，通过调节锌转运蛋白ZIP14，TAS2R43被证明对永生化壁细胞中过量锌积累具有保护作用。
