碳酸酐酶 IV 升高细胞 pH 值后，人鼻黏膜纤毛上皮细胞中 CO/HCO-自由溶液可降低纤毛运动。

Ciliary Motility Decreased by a CO/HCO-Free Solution in Ciliated Human Nasal Epithelial Cells Having a pH Elevated by Carbonic Anhydrase IV.

机构信息

Research Laboratory for Epithelial Physiology, Research Organization of Science and Technology, Ritsumeikan University BKC, Kusatsu 525-8577, Japan.

Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

出版信息

Int J Mol Sci. 2024 Aug 21;25(16):9069. doi: 10.3390/ijms25169069.

DOI:10.3390/ijms25169069

PMID:39201753

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11354224/

Abstract

An application of CO/HCO-free solution (Zero-CO) did not increase intracellular pH (pH) in ciliated human nasal epithelial cells (c-hNECs), leading to no increase in frequency (CBF) or amplitude (CBA) of the ciliary beating. This study demonstrated that the pH of c-hNECs expressing carbonic anhydrase IV (CAIV) is high (7.64), while the pH of ciliated human bronchial epithelial cells (c-hBECs) expressing no CAIV is low (7.10). An extremely high pH of c-hNECs caused pH, CBF and CBA to decrease upon Zero-CO application, while a low pH of c-hBECs caused them to increase. An extremely high pH was generated by a high rate of HCO influx via interactions between CAIV and Na/HCO cotransport (NBC) in c-hNECs. An NBC inhibitor (S0859) decreased pH, CBF and CBA and increased CBF and CBA in c-hNECs upon Zero-CO application. In conclusion, the interactions of CAIV and NBC maximize HCO influx to increase pH in c-hNECs. This novel mechanism causes pH to decrease, leading to no increase in CBF and CBA in c-hNECs upon Zero-CO application, and appears to play a crucial role in maintaining pH, CBF and CBA in c-hNECs periodically exposed to air (0.04% CO) with respiration.

摘要

CO/HCO 自由溶液（零 CO）的应用并未增加纤毛人鼻上皮细胞（c-hNEC）中的细胞内 pH（pH），导致纤毛摆动的频率（CBF）或幅度（CBA）没有增加。本研究表明，表达碳酸酐酶 IV（CAIV）的 c-hNEC 的 pH 值较高（7.64），而不表达 CAIV 的纤毛人支气管上皮细胞（c-hBEC）的 pH 值较低（7.10）。c-hNEC 中的极高 pH 值导致 pH、CBF 和 CBA 在应用零 CO 后降低，而 c-hBEC 中的低 pH 值导致它们增加。极高的 pH 值是由 CAIV 与 c-hNEC 中的 Na/HCO 共转运蛋白（NBC）之间的相互作用导致 HCO 内流率高而产生的。NBC 抑制剂（S0859）降低了 pH、CBF 和 CBA，并增加了 c-hNEC 中 Zero-CO 应用后的 CBF 和 CBA。总之，CAIV 和 NBC 的相互作用最大限度地增加了 HCO 的内流，从而增加了 c-hNEC 中的 pH 值。这种新的机制导致 pH 值下降，导致 c-hNEC 中 Zero-CO 应用后 CBF 和 CBA 没有增加，并且似乎在周期性暴露于呼吸空气中（0.04% CO）的 c-hNEC 中维持 pH、CBF 和 CBA 方面发挥着关键作用。