Airway Ciliary Beating Affected by the Dose-Dependent [Ca] Increase in Down Syndrome Mice, Ts1Rhr.

In Ts1Rhr, a Down syndrome model mouse, the airway ciliary beatings are impaired; that is, decreases in ciliary beat frequency (CBF) and ciliary bend angle (CBA, an index of ciliary beat amplitude)). A resumption to two copies of the gene on the Ts1Rhr trisomic segment (Ts1Rhr:) rescues the decreases in CBF and CBA that occur in Ts1Rhr. In airway cilia, upon stimulation with procaterol (a β-agonist), the CBF increase is slower over the time course than the CBA increase because of cAMP degradation by Ca/calmodulin-dependent phosphodiesterase 1 (PDE1) existing in the metabolon regulating CBF.

Enhancement of ciliary beat amplitude by carbocisteine in ciliated human nasal epithelial cells.

Objective: Carbocisteine (CCis), a mucoactive agent, is used to improve the symptoms of sinonasal diseases. However, the effect of CCis on nasal ciliary beating remains uncertain. We examined the effects of CCis on ciliary beat distance (CBD, an index of amplitude), and ciliary beat frequency (CBF) in ciliated human nasal epithelial cells (cHNECs) in primary culture.

Ciliary beating amplitude controlled by intracellular Cl and a high rate of CO production in ciliated human nasal epithelial cells.

The ciliary transport is controlled by two parameters of the ciliary beating, frequency (CBF) and amplitude. In this study, we developed a novel method to measure both CBF and ciliary bend distance (CBD, an index of ciliary beating amplitude) in ciliated human nasal epithelial cells (cHNECs) in primary culture, which are prepared from patients contracting allergic rhinitis and chronic sinusitis. An application of Cl-free NO solution or bumetanide (an inhibitor of Na/K/2Cl cotransport), which decreases intracellular Cl concentration ([Cl]), increased CBD, not CBF, at 37 °C; however, it increased both CBD and CBF at 25 °C.

Daidzein-Stimulated Increase in the Ciliary Beating Amplitude via an [Cl] Decrease in Ciliated Human Nasal Epithelial Cells.

The effects of the isoflavone daidzein on the ciliary beat distance (CBD, which is a parameter assessing the amplitude of ciliary beating) and the ciliary beat frequency (CBF) were examined in ciliated human nasal epithelial cells (cHNECs) in primary culture. Daidzein decreased [Cl] and enhanced CBD in cHNECs. The CBD increase that was stimulated by daidzein was mimicked by Cl-free NO₃ solution and bumetanide (an inhibitor of Na⁺/K⁺/2Cl cotransport), both of which decreased [Cl] Moreover, the CBD increase was inhibited by 5-Nitro-2-(3-phenylpropylamino)benzoic acid (NPPB, a Cl channel blocker), which increased [Cl].

Spontaneous oscillation of the ciliary beat frequency regulated by release of Ca from intracellular stores in mouse nasal epithelia.

Ciliary beating frequency (CBF) was investigated in ciliated nasal epithelial cells (cMNECs) isolated from mice using video microscopy equipped with a high-speed camera. In cMNECs, a spontaneous CBF oscillation was observed. The CBF oscillation was abolished by BAPTA-AM but not by Ca-free solution.

Carbocisteine stimulated an increase in ciliary bend angle via a decrease in [Cl] in mouse airway cilia.

Carbocisteine (CCis), a mucoactive agent, is widely used to improve respiratory diseases. This study demonstrated that CCis increases ciliary bend angle (CBA) by 30% and ciliary beat frequency (CBF) by 10% in mouse airway ciliary cells. These increases were induced by an elevation in intracellular pH (pH; the pH pathway) and a decrease in the intracellular Cl concentration ([Cl]; the Cl pathway) stimulated by CCis.

Translin modulates mesenchymal cell proliferation and differentiation in mice.

Translin, a highly conserved DNA/RNA binding protein that forms a hetero-octamer together with Translin-associated factor X (TRAX), possesses a broad variety of functions, including RNA processing and DNA repair. Recent studies have reported that Translin is involved in mesenchymal cell physiology. Thus, here we analyzed the intrinsic role of Translin in mesenchymal cell proliferation and differentiation.

Seihai-to (TJ-90)-Induced Activation of Airway Ciliary Beatings of Mice: Ca Modulation of cAMP-Stimulated Ciliary Beatings via PDE1.

Sei-hai-to (TJ-90, Qing Fei Tang), a Chinese traditional medicine, increases ciliary beat frequency (CBF) and ciliary bend angle (CBA) mediated via cAMP (3',5'-cyclic adenosine monophosphate) accumulation modulated by Ca-activated phosphodiesterase 1 (PDE1A). A high concentration of TJ-90 (≥40 μg/mL) induced two types of CBF increases, a transient increase (an initial increase, followed by a decrease) and a sustained increase without any decline, while it only sustained the CBA increase. Upon inhibiting increases in intracellular Ca concentration ([Ca]) by 10 μM BAPTA-AM (Ca-chelator, 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) or Ca/calmodulin-dependent PDE1 by 8MmIBMX (a selective PDE1 inhibitor), TJ-90 (400 μg/mL) induced only the sustained CBF increase without any transient CBF increase.

Measurement of [Cl] unaffected by the cell volume change using MQAE-based two-photon microscopy in airway ciliary cells of mice.

MQAE is a 'non-ratiometric' chloride ion (Cl)-quenched fluorescent indicator that is used to determine intracellular Cl concentration ([Cl]). MQAE-based two-photon microscopy is reported to be a useful method to measure [Cl], but it is still controversial because a change in cell volume may alter the MQAE concentration, leading to a change in the fluorescence intensity without any change in [Cl]. In an attempt to elucidate the effect or lack of effect of cell volume on MQAE concentration, we studied the effects of changes in cell volume, achieved by applying different levels of osmotic stress, on the intensity of MQAE fluorescence in airway ciliary cells.

[Ca ] modulation of cAMP-stimulated ciliary beat frequency via PDE1 in airway ciliary cells of mice.

What is the central question of this study? The ciliary beat frequency (CBF) of the airway is controlled by [Ca ] . However, the effects of a reduction in [Ca ] on CBF are still controversial (an increase, a decrease or no change). What is the main finding and its importance? This study demonstrated that [Ca ] directly regulates CBF (direct action) and also indirectly regulates CBF via cAMP accumulation controlled by Ca -dependent PDE1 activity (indirect action).

A low [Ca]-induced enhancement of cAMP-activated ciliary beating by PDE1A inhibition in mouse airway cilia.

This study demonstrated that PDE1 (phosphodiesterase 1) existing in the ciliary beat frequency (CBF)-regulating metabolon regulates CBF in procaterol-stimulated lung airway ciliary cells of mouse. Procaterol (an β-agonist) increased the ciliary bend angle (CBA) and CBF via cAMP accumulation in the ciliary cells of mice: interestingly, the time course of CBF increase was slower than that of CBA increase. However, IBMX (3-isobutyl-1-methylxanthine, an inhibitor of PDE) increased CBA and CBF in an identical time course.

Quercetin is a Useful Medicinal Compound Showing Various Actions Including Control of Blood Pressure, Neurite Elongation and Epithelial Ion Transport.

Quercetin has multiple potential to control various cell function keeping our body condition healthy. In this review article, we describe the molecular mechanism on how quercetin exerts its action on blood pressure, neurite elongation and epithelial ion transport based from a viewpoint of cytosolic Cl- environments, which is recently recognized as an important signaling factor in various types of cells. Recent studies show various roles of cytosolic Cl- in regulation of blood pressure and neurite elongation, and prevention from bacterial and viral infection.