a Department of Physiology , College of Medicine, Gachon University , Incheon , Republic of Korea.
b Department of Oral Biology , BK21 PLUS Project, College of Dentistry, Yonsei University , Seoul , Republic of Korea.
J Enzyme Inhib Med Chem. 2019 Dec;34(1):179-188. doi: 10.1080/14756366.2018.1540475.
Patients carrying the carbonic anhydrase12 E143K mutation showed the dry mouth phenotype. The mechanism underlying the modulation of aquaporin 5 and function in the salivary glands by carbonic anhydrase12 remains unknown. In this study, we identified the mislocalised aquaporin 5 in the salivary glands carrying the E143K. The intracellular pH of E143K cells was more acidic than that of the cells carrying wild type. To evaluate the role of carbonic anhydrase12 on the volume regulation of aquaporin 5, the submandibular gland cells were subjected to hypotonic stimuli. E143K enhanced the extent of swelling of cells on hypotonicity. Aquaporin 5 modulates water influx through ion transporters to prevent osmotic imbalance. These results suggest that the carbonic anhydrase12 E143K, including acidification or inflammation, mediates volume dysregulation by the loss of aquaporin 5. Thus, carbonic anhydrase12 may determine sensible effects on the cellular osmotic regulation by modulating aquaporin 5.
携带碳酸酐酶 12 E143K 突变的患者表现出口干表型。碳酸酐酶 12 调节水通道蛋白 5 的机制及其在唾液腺中的功能尚不清楚。在这项研究中，我们鉴定了携带 E143K 的唾液腺中定位错误的水通道蛋白 5。E143K 细胞的细胞内 pH 值比携带野生型的细胞更酸性。为了评估碳酸酐酶 12 对水通道蛋白 5 体积调节的作用，将颌下腺细胞暴露于低渗刺激下。E143K 增强了细胞在低渗时的肿胀程度。水通道蛋白 5 通过离子转运蛋白调节水流入以防止渗透失衡。这些结果表明，碳酸酐酶 12 E143K 通过丧失水通道蛋白 5 介导体积失调，包括酸化或炎症。因此，碳酸酐酶 12 可能通过调节水通道蛋白 5 对细胞渗透压调节产生敏感影响。
