Biomedical subjects

Qunying Hong

Publications and source records attributed to Qunying Hong.

3 recordsLinked to original sources

PubMed2007

Conformationally altered hyaluronan restricts complement classical pathway activation by binding to C1q, C1r, C1s, C2, C5 and C9, and suppresses WOX1 expression in prostate DU145 cells.

Linear non-sulfated hyaluronan (HA) does not bind complement proteins yet inhibits their hemolytic function. We have previously induced the complement inhibitory function of HA by heat treatment. However, heated HA readily loses its anti-complementary activity probably due to instantaneous interchain re-association. Here, HA solutions were heated and then freeze-dried. Compared to native HA, heated/freeze-dried HA stably restricted serum complement-mediated hemolysis via the classical pathway, in which serum C1 hemolytic function and C3 activation were blocked. Also, treated HA had a significantly increased binding of component C1q, C1r, C1s, C2, C5, C9, P, D and H. Further, when HA was gel-fractionated by electrophoresis and then freeze-dried, its anti-complementary activity was stably induced. Both native and heated/freeze-dried HA stimulated ERK phosphorylation in prostate DU145 cells. However, treated HA suppressed the expression of tumor suppressors WOX1 and WOX2. Together, HA with an altered conformation stabilizes its inhibition and binding of complement proteins. It may recognize cell surface receptors differently from native HA, thereby differentially regulating the expression of cellular proteins.

Cell Line, Tumor↗

PubMed2005

WOX1 is essential for tumor necrosis factor-, UV light-, staurosporine-, and p53-mediated cell death, and its tyrosine 33-phosphorylated form binds and stabilizes serine 46-phosphorylated p53.

WW domain-containing oxidoreductase WOX1, also named WWOX or FOR, undergoes Tyr33 phosphorylation at its first N-terminal WW domain and subsequent nuclear translocation in response to sex steroid hormones and stress stimuli. The activated WOX1 binds tumor suppressor p53, and both proteins may induce apoptosis synergistically. Functional suppression of WOX1 by antisense mRNA or a dominant negative abolishes p53-mediated apoptosis. Here, we determined that UV light, anisomycin, etoposide, and hypoxic stress rapidly induced phosphorylation of p53 at Ser46 and WOX1 at Tyr33 (phospho-WOX1) and their binding interactions in several tested cancer cells. Mapping by yeast two-hybrid analysis and co-immunoprecipitation showed that phospho-WOX1 physically interacted with Ser46-phosphorylated p53. Knockdown of WOX1 protein expression by small interfering RNA resulted in L929 fibroblast resistance to apoptosis by tumor necrosis factor, staurosporine, UV light, and ectopic p53, indicating an essential role of WOX1 in stress stimuli-induced apoptosis. Notably, UV light could not induce p53 protein expression in these WOX1 knockdown cells, although p53 mRNA levels were not reduced. Suppression of WOX1 by dominant negative WOX1 (to block Tyr33 phosphorylation) also abolished UV light-induced p53 protein expression. Time course analysis showed that the stability of ectopic wild type p53, tagged with DsRed, was decreased in WOX1 knockdown cells. Inhibition of MDM2 by nutlin-3 increased the binding of p53 and WOX1 and stability of p53. Together, our data show that WOX1 plays a critical role in conferring cellular sensitivity to apoptotic stress and that Tyr33 phosphorylation in WOX1 is essential for binding and stabilizing Ser46-phosphorylated p53.

Active Transport, Cell Nucleus↗

PubMed2003

Effect of continuous hemofiltration on hemodynamics, lung inflammation and pulmonary edema in a canine model of acute lung injury.

OBJECTIVE: This study examined whether continuous hemofiltration favorably affects cardiopulmonary variables, lung inflammation, and lung fluid balance in a canine model of oleic acid induced acute lung injury. METHODS: Eleven pentobarbital-anesthetized dogs were randomly divided into a control (mechanical ventilation, MV) group (n=6) and a MV plus hemofiltration (HF) group (n=5). All animals received an intravenous injection of oleic acid (0.09 ml/kg) to induce acute lung injury. Continuous arterial-venous hemofiltration (blood flow 100 ml/min, ultrafiltration rate at 50-65 ml kg(-1) h(-1)) was started after establishment of oleic acid induced acute lung injury and continued for 4 h. Hemodynamics, lung mechanics, gas exchange, lung fluid balance, lung histology, and the level of plasma cytokines were assessed. RESULTS: After 240 min of HF treatment there was a significant increase in cardiac output, reduction in pulmonary arterial pressure, and improvement in both oxygenation and lung mechanics. Also, in the HF group the lung wet-to-dry weight ratio was significantly reduced. Histologically, HF reduced edema and inflammatory cell infiltration in the lung. There was also a significantly greater decrease in plasma IL-6 and IL-8 levels in the HF group than in group receiving MV alone. CONCLUSIONS: In a canine model of acute lung injury continuous HF improved cardiopulmonary function, reduced pulmonary edema, decreased lung permeability and inflammation, and decreased the plasma concentration of proinflammatory cytokines.

Albumins↗