Annexin A2, a multifunctional tumor associated protein, promotes nuclear factor-kappa B (NF-κB) activation by interacting with NF-κB p50 subunit and facilitating its nuclear translocation. Here we demonstrated that two ginsenosides Rg5 (G-Rg5) and Rk1 (G-Rk1), with similar structure, directly bound to Annexin A2 by molecular docking and cellular thermal shift assay. Both Rg5 and Rk1 inhibited the interaction between Annexin A2 and NF-κB p50 subunit, their translocation to nuclear and NF-κB activation. Inhibition of NF-κB by these two ginsenosides decreased the expression of inhibitor of apoptosis proteins (IAPs), leading to caspase activation and apoptosis. Over expression of K302A Annexin A2, a mutant version of Annexin A2, which fails to interact with G-Rg5 and G-Rk1, effectively reduced the NF-κB inhibitory effect and apoptosis induced by G-Rg5 and G-Rk1. In addition, the knockdown of Annexin A2 largely enhanced NF-κB activation and apoptosis induced by the two molecules, indicating that the effects of G-Rg5 and G-Rk1 on NF-κB were mainly mediated by Annexin A2. Taken together, this study for the first time demonstrated that G-Rg5 and G-Rk1 inhibit tumor cell growth by targeting Annexin A2 and NF-κB pathway, and G-Rg5 and G-Rk1 might be promising natural compounds for targeted cancer therapy.
Active Transport, Cell Nucleus ; drug effects ; Annexin A2 ; chemistry ; deficiency ; genetics ; metabolism ; Antineoplastic Agents ; chemistry ; metabolism ; pharmacology ; Apoptosis ; drug effects ; Biological Products ; chemistry ; metabolism ; pharmacology ; Cell Nucleus ; drug effects ; metabolism ; Down-Regulation ; drug effects ; Drug Discovery ; Gene Knockdown Techniques ; Ginsenosides ; chemistry ; Hep G2 Cells ; Humans ; Molecular Docking Simulation ; Molecular Targeted Therapy ; NF-kappa B p50 Subunit ; metabolism ; Protein Conformation

Iodide uptake across the membranes of thyroid follicular cells and cancer cells occurs through an active transport process mediated by the sodium-iodide symporter (NIS). The rat and human NIS-coding genes were cloned and identified in 1996. Evaluation of NIS gene and protein expression is critical for the management of thyroid cancer, and several approaches to increase NIS levels have been tried. Identification of the NIS gene has provided a means of expanding its role in radionuclide therapy and molecular target-specific theragnosis (therapy and diagnosis using the same molecular target). In this article, we describe the relationship between NIS expression and the thyroid carcinoma treatment using I-131 and alternative therapeutic approaches.
Animals ; Biological Transport, Active ; Clone Cells ; Diagnosis ; Humans ; Ion Transport ; Membranes ; Rats ; Thyroid Gland ; Thyroid Neoplasms*

The effect of Carteolol hydrocholride on the Na-K ATPase of anterior capsule and epithelium of cattle lens has been investigated. The experiments were also designed to determine the action of Carteolol hydrochloride on the Na-K ATPase activity in anterior capsule and epithelium of cattle lens. The following results were observed. 1. The predominent location of Na-K ATPase was located in the epithelim and NaK ATPase was closely related with active trasport system of sodium and potassium in the lens epithelium. 2. The activity of Na-K ATPase of cattle lens epithelium was alomst totally inhibited by Ouabain. 3. Beta-adrenergic blocking agent(Carteolol hydrochloride) in the epithelium of cattle lens was shown to be actively transported by the ATPase. 4. The Na-K ATPase activity of cattle lens epithelium was inhibited by Carteolol hydrochloride.
Adenosine Triphosphatases* ; Animals ; Biological Transport, Active ; Carteolol* ; Cattle* ; Epithelial Cells* ; Epithelium ; Membranes* ; Ouabain ; Potassium ; Sodium

Time delay between medial contact and treatment in symptomatic patients with acute myocardial infarction (AMI) is the most important factor in the prediction of short and long-term mortality. The incidences of AMI has been increased in Korea rapidly. According to Korea Acute Myocardial Infarction Registry (KAMIR), pre-hospital delay is longer in Korean patients compared with Western patients, especially in patients with non-ST elevation myocardial infarction and in elderly female patients. Prompt seeking medical care in patients with suspected symptom of AMI can be achieved through patient and patient's family education, active transportation system of ambulance, and good cooperations of regional emergency centers. Shortening time delay in treatment of AMI will save patient's life and reduce medical costs in the future, especially in Korea.
Aged ; Ambulances ; Biological Transport, Active ; Emergencies ; Female ; Humans ; Incidence ; Korea ; Myocardial Infarction

Congenital chloridorrhea is a rare autosomal recessive disease and results from impairment of active transport of chloride in the ileum and colon. Absence of the Cl-/HCO3-, exchange pump causes polyhydramnios, distended bowel loop and absence of meconium before birth. Prenatal ultrasound examination shows a great number of circular anechoic area in the fetal abdomen, as well as polyhydramnios. Massive watery diarrhea is apparent from the first days of life. This fluid loss, with its attendant impairment of electrolyte homeostasis, is life threatening. Exact replacement of water, NaCl and KCl can prevent the growth and psychomotor retardation and the development of progressive renal damage. We experienced one case of congenital chloridorrhea and present it with brief review of literatures.
Abdomen ; Biological Transport, Active ; Colon ; Diarrhea ; Homeostasis ; Ileum ; Meconium ; Parturition ; Polyhydramnios ; Ultrasonography ; Water

Animals ; Biological Transport, Active/physiology* ; Centrioles/metabolism* ; Cilia/metabolism* ; Mice ; Mice, Mutant Strains ; N-Acetylglucosaminyltransferases/metabolism*

Normally the cornea has a water content varying between 76-78%, a state of relative dehydration maintained through its own metabolism by the active transport of water and ions across its limiting membrane, the epithelium and endothelium. If the metabolism is grossly disturbed or if the effectivity of the limiting membrane is impaired, the living cornea will swell by the absorption of the fluid. Corneal edema are developed due to trauma, inflammation, glaucoma, degeneration, and neuropathic and metabolic conditions. Essential corneal edema are encountered for which no cause can be found, the condition apparantly occuring without other ocular pathology. A 29 years old Korean lady has been found to have bilateral essential edema of the cornea.
Absorption ; Adult ; Biological Transport, Active ; Cornea ; Corneal Edema* ; Dehydration ; Edema ; Endothelium ; Epithelium ; Glaucoma ; Humans ; Inflammation ; Ions ; Membranes ; Metabolism ; Pathology ; Water

PURPOSE: alpha-Ketoglutarate (alphaKG), a Krebs cycle intermediate, is extensively used in the kidney as a fuel substrate and as a counter anion for organic acid secretion. It is known to be taken up by the proximal tubule cells via the brush-border as well as basolateral membranes. We explored biochemical characteristics of the brush-border and basolateral alphaKG transport systems in pars convoluta and pars recta of the proximal tubule, respectively. METHODS: Brush-border and basolateral membrane vesicles (BBMV and BLMV) were isolated from rabbit renal outer cortex and outer medulla by Percoll gradient centrifugation. Vesicular uptake of alphaKG was determined by rapid Millipore filtration method using alpha-14[C]KG as a substrate. RESULTS: Both BBMV and BLMV showed a Na-gradient dependent uphill transport of alphaKG. The systems in both membranes were similarly inhibited by Li and activated by Na (Hill coefficient of 1.4). Kinetic analyses indicated that the Na-alphaKG cotransporters in the BBMV had a lower substrate affinity as compared with those in the BLMV. The transport systems in BLMVs showed a similar Km but different Vmax between the outer cortex (Km: 34 uM, Vmax: 3.3 nmol/mg protein/10s) and outer medulla (Km: 37, Vmax: 1.8). On the other hand, the systems in BBMVs were different in both Km and Vmax between the outer cortex (Km: 194, Vmax: 3.3) and outer medulla (Km: 89, Vmax: 1.7). CONCLUSION: The findings suggest that both axial and apical to basolateral heterogeneity of the Na-alphaKG cotransport system in proximal tubules may be due to a physiological adaptation to efficiently utilize alphaKG in the kidney.
Adaptation, Physiological ; Biological Transport, Active ; Centrifugation ; Citric Acid Cycle ; Filtration ; Hand ; Ketoglutaric Acids ; Kidney Tubules ; Kidney* ; Membranes ; Population Characteristics ; Symporters

BACKGROUND: Airway secretions partly arise from the interstitial fluid and partly from the secretory activities of respiratory epithelium and submucosal gland. The flow of water across the tracheobronchial epithelium is likely to be an important determinant of the efficiency of mucociliary clearance. Water movement across the epithelium is thought to follow active ion transport passively by means of the osmotic gradients created. OBJECTIVES: The aim of this study was to determine whether Na, K, and Cl are transported actively by the epithelium of nasal mucosa and to evaluate an effect of the tracheostomy on changes of pH and electrolytes in nasal secretum. MATERIALS AND METHODS: pH and Na, K, and Cl values were estimated in 35 samples (20 tracheostomized patients and 15 normal persons) of nasal secretum and plasma. RESULTS: On 15 normal persons, Mean pH value was 7.43, Na 143.2, K 4.2 and Cl 109.1(mEq/L) in plasma and Mean pH value was 7.81, Na 139.7, K 11.5 and Cl 127.5(mEq/L) in nasal secretion. On 20 tracheostomized patients, pH 7.49, Na 140.2, K 3.8, and Cl 108.7(mEq/L) in plasma were estimated, and pH 7.88, Na 128.5, K 12.0, and Cl 121.5(mEq/L) were estimated in nasal secretum. In nasal secretum pH, K, and Cl were higher than in plasma by +0.39, +8.2 and +12.8(mEq/L) respectively, while Na was lower -11.6(mEq/L). We had the same result on normal persons as on tracheostomized patients. The results show that pH, K and Cl were higher in nasal secretion and Na was lower than in plasma. CONCLUSION: Significant difference of pH and electrolyte values in nasal secretion was not observed between normal person and tracheostomized patient.
Biological Transport, Active ; Electrolytes ; Epithelium ; Extracellular Fluid ; Humans ; Hydrogen-Ion Concentration* ; Ion Transport ; Mucociliary Clearance ; Nasal Mucosa ; Plasma ; Respiratory Mucosa ; Tracheostomy ; Water Movements

Effects of cadmium (Cd) intoxication on renal endosomal accumulation of organic cations (OC ) were studied in rats using 14C-tetraethylammnium (TEA) as a substrate. Cd intoxication was induced by s.c. injections of 2 mg Cd/kg/day for 2-3 weeks. Renal cortical endosomes were isolated and the endosomal acidification (acridine orange fluorescence change) and TEA uptake (Millipore filtration technique) were assessed. The TEA uptake was an uphill transport mediated by H /OC antiporter driven by the pH gradient established by H -ATPase. In endosomes of Cd-intoxicated rats, the ATP-dependent TEA uptake was markedly attenuated due to inhibition of endosomal acidification as well as H /TEA antiport. In kinetic analysis of H /TEA antiport, Vmax was reduced and Km was increased in the Cd group. Inhibition of H /TEA antiport was also observed in normal endosomes directly exposed to free Cd (but not Cd-metallothionein complex, CdMt) in vitro. These data suggest that during chronic Cd exposure, free Cd ions liberated by lysosomal degradation of CdMt in proximal tubule cells may impair the endosomal accumulation of OC by directly inhibiting the H /OC antiporter activity and indirectly by reducing the intravesicular acidification, the driving force for H /OC exchange.
Animals ; Biological Transport, Active ; Cadmium ; Cations ; Citrus sinensis ; Endosomes* ; Filtration ; Fluorescence ; Ion Transport ; Ions ; Kidney ; Proton-Motive Force ; Rats* ; Tea ; Tetraethylammonium*