58 research outputs found
Impaired Regulatory Volume Decrease in Freshly Isolated Cholangiocytes from Cystic Fibrosis Mice: IMPLICATIONS FOR CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR EFFECT ON POTASSIUM CONDUCTANCE
Various K(+) and Cl(-) channels are important in cell volume regulation and biliary secretion, but the specific role of cystic fibrosis transmembrane conductance regulator in cholangiocyte cell volume regulation is not known. The goal of this research was to study regulatory volume decrease (RVD) in bile duct cell clusters (BDCCs) from normal and cystic fibrosis (CF) mouse livers. Mouse BDCCs without an enclosed lumen were prepared as described (Cho, W. K. (2002) Am. J. Physiol. 283, G1320-G1327). The isotonic solution consisted of HEPES buffer with 40% of the NaCl replaced with isomolar amounts of sucrose, whereas hypotonic solution was the same as isotonic solution without sucrose. The cell volume changes were indirectly assessed by measuring cross-sectional area (CSA) changes of the BDCCs using quantitative videomicroscopy. Exposure to hypotonic solutions increased relative CSAs of normal BDCCs to 1.20 +/- 0.01 (mean +/- S.E., n = 50) in 10 min, followed by RVD to 1.07 +/- 0.01 by 40 min. Hypotonic challenge in CF mouse BDCCs also increased relative CSA to 1.20 +/- 0.01 (n = 53) in 10 min but without significant recovery. Coadministration of the K(+)-selective ionophore valinomycin restored RVD in CF mouse BDCCs, suggesting that the impaired RVD was likely from a defect in K(+) conductance. Moreover, this valinomycin-induced RVD in CF mice was inhibited by 5-nitro-2'-(3-phenylpropylamino)-benzoate, indicating that it is not from nonspecific effects. Neither cAMP nor calcium agonists could reverse the impaired RVD seen in CF cholangiocytes. Our conclusion is that CF mouse cholangiocytes have defective RVD from an impaired K(+) efflux pathway, which could not be reversed by cAMP nor calcium agonists
TCTAP A-121 Transradial Versus Transfemoral Intervention in ST-segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention with Drug-eluting Stents
Non-Calcified Ductal Carcinoma in Situ: Ultrasound and Mammographic Findings Correlated with Histological Findings
TCTAP A-001 Twelve-month Clinical Outcomes of Transradial Coronary Artery Intervention: Comparison of the Right and Left Radial Artery Approach
Comparison of 2-year mortality according to obesity in stabilized patients with type 2 diabetes mellitus after acute myocardial infarction: results from the DIAMOND prospective cohort registry
An Essential Regulatory Role of Downstream of Kinase-1 in the Ovalbumin-Induced Murine Model of Asthma
The downstream of kinase (DOK)-1 is involved in the protein tyrosine kinase (PTK) pathway in mast cells, but the role of DOK-1 in the pathogenesis of asthma has not been defined. In this study, we have demonstrated a novel regulatory role of DOK-1 in airway inflammation and physiologic responses in a murine model of asthma using lentiviral vector containing DOK-1 cDNA or DOK-1-specific ShRNA. The OVA-induced inflammatory cells, airway hyperresponsiveness, Th2 cytokine expression, and mucus response were significantly reduced in DOK-1 overexpressing mice compared to OVA-challenged control mice. The transgenic introduction of DOK-1 significantly stimulated the activation and expression of STAT-4 and T-bet, while impressively inhibiting the activation and expression of STAT-6 and GATA-3 in airway epithelial cells. On the other hand, DOK-1 knockdown mice enhanced STAT-6 expression and its nuclear translocation compared to OVA-challenged control mice. When viewed in combination, our studies demonstrate DOK-1 regulates allergen-induced Th2 immune responses by selective stimulation and inhibition of STAT-4 and STAT-6 signaling pathways, respectively. These studies provide a novel insight on the regulatory role of DOK-1 in allergen-induced Th2 inflammation and airway responses, which has therapeutic potential for asthma and other allergic diseases
Correction: Comparison of 2âyear mortality according to obesity in stabilized patients with type 2 diabetes mellitus after acute myocardial infarction: results from the DIAMOND prospective cohort registry
Electrophysiological characterization of volume-activated chloride currents in mouse cholangiocyte cell line
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