Cystic fibrosis（CF） is a severe genetic disease caused by the gene mutation of the cystic fibrosis transmembrane conductance regulator（CFTR） chloride channel. The most common point mutation AF508, which leads to i...Cystic fibrosis（CF） is a severe genetic disease caused by the gene mutation of the cystic fibrosis transmembrane conductance regulator（CFTR） chloride channel. The most common point mutation AF508, which leads to impaired intracellular processing and channel gating of CFTR, appears in about 90% CF patients. The natural compound curcumin was reported to correct the processing defect of AF508-CFTR and proposed as a potential therapeutic drug to cure CF. In the present study, we analyzed the effect of curcumin on AF508-CFTR and demonstrated that curcumin can restore the impaired chloride conductance of AF508 mutant CFTR. The activity is rapid, reversible and cAMP-dependent. However, we couldn＇t reproduce the previously reported correction of the defective membrane trafficking of AF508-CFTR by curcumin. Therefore, curcumin may not be a superior lead compound for developing anti-CF drugs.展开更多
Previous studies reported that capsaicin potentiates AF508 mutant cystic fibrosis transmembrane conductance regulator（CFTR） channel gating defect by transfected cell-based assays. It has been postulated that orally ...Previous studies reported that capsaicin potentiates AF508 mutant cystic fibrosis transmembrane conductance regulator（CFTR） channel gating defect by transfected cell-based assays. It has been postulated that orally ingested capsaicin may conceptually be used to develop a therapeutic strategy to treat gastrointestinal disorders in CF patients. We tried to reproduce and extend those pre-clinical data of previous studies. Cell-based fluorescence func- tional measurements in Fischer thyroid epithelial cells（FRT） expressing CFTR showed no effect of capsaicin on potentiating AF508-CFTR, while genistein showed a strongly positive activity. Studies show that capsaicin and dihy- drocapsaicin activated cAMP-prestimulated wild-type CFTR in a dose-dependent manner with a maximal response of 70% of that activated by genistein, thus gave an apparent EC50 of （40.4±6.8）μmol/L and （150.2±7.4） μtmol/L respectively. Preliminary study shows that the binding sites for capsaicin and dihydrocapsaicin may be probably partially overlapped with that for genistein because the maximal activation of wild-type CFTR with genistein is partially blocked by caosaicin and dihydrocapsaicin.展开更多
Theophylline has been widely used in the＇treatment of airway disease but molecular mechanism has not been clearly elucidated. Previous studies have manifested that theophylline increases intracellular cAMP concentra-...Theophylline has been widely used in the＇treatment of airway disease but molecular mechanism has not been clearly elucidated. Previous studies have manifested that theophylline increases intracellular cAMP concentra- tion. Because cystic fibrosis transmembrane conductance regulator（CFTR） is a cAMP-dependent Cl- channel that plays key roles in fluid secretion in vivo, we postulated that theophylline activates CFTR channel gating. We found （1） theophylline stimulated CFTR-mediated anion transport in a concentration-dependent manner, and CFTR specific blocker completely reversed the effect; （2） theophylline had no effect on △F508 or G551D mutant CFTR chloride channel activity; （3） theophylline had additive effect with forskolin（FSK） and 3-isobutyl-xanthin（IBMX）, thus a direct binding activation mechanism was suggested. In conclusion, the results may provide a clue to elucidating the molecular mechanism of theophylline activities and theophylline may present a novel lead drug in treating CFTR-related disease.展开更多
Recent studies on the inhibition of tumor growth by Se-containing polysaccharide were reviewed.Meanwhile,the possible molecular mechanisms of the inhibition of tumor cell growth through antioxidation,induction of tumo...Recent studies on the inhibition of tumor growth by Se-containing polysaccharide were reviewed.Meanwhile,the possible molecular mechanisms of the inhibition of tumor cell growth through antioxidation,induction of tumor cell apoptosis,blockade of cell cycle,and enhancement of immunity by Se-containing polysaccharide were proposed.In the end,the potential application of Se-containing polysaccharide in the prevention and treatment of tumor was elucidated.展开更多
基金Supported by the National Natural Science Foundation for Distinguished Young Scholars(No30325011)National Natural Science Foundation of China(Nos30570864 and 30670477)Program for New Century Excellent Talents in University(No NCET-07-0406)
文摘Cystic fibrosis（CF） is a severe genetic disease caused by the gene mutation of the cystic fibrosis transmembrane conductance regulator（CFTR） chloride channel. The most common point mutation AF508, which leads to impaired intracellular processing and channel gating of CFTR, appears in about 90% CF patients. The natural compound curcumin was reported to correct the processing defect of AF508-CFTR and proposed as a potential therapeutic drug to cure CF. In the present study, we analyzed the effect of curcumin on AF508-CFTR and demonstrated that curcumin can restore the impaired chloride conductance of AF508 mutant CFTR. The activity is rapid, reversible and cAMP-dependent. However, we couldn＇t reproduce the previously reported correction of the defective membrane trafficking of AF508-CFTR by curcumin. Therefore, curcumin may not be a superior lead compound for developing anti-CF drugs.
基金Supported by New Century Excellent Talents Program in University(No.NCET-07-0406)Liaoning Excellent Talents Pro-gram in University(No.2006R33)+1 种基金Dalian Municipal Science and Technology Fund(No.2006J23JH018)Science and Tech-nology Fund from the Education Department of Liaoning Province, China(No.20060492).
文摘Previous studies reported that capsaicin potentiates AF508 mutant cystic fibrosis transmembrane conductance regulator（CFTR） channel gating defect by transfected cell-based assays. It has been postulated that orally ingested capsaicin may conceptually be used to develop a therapeutic strategy to treat gastrointestinal disorders in CF patients. We tried to reproduce and extend those pre-clinical data of previous studies. Cell-based fluorescence func- tional measurements in Fischer thyroid epithelial cells（FRT） expressing CFTR showed no effect of capsaicin on potentiating AF508-CFTR, while genistein showed a strongly positive activity. Studies show that capsaicin and dihy- drocapsaicin activated cAMP-prestimulated wild-type CFTR in a dose-dependent manner with a maximal response of 70% of that activated by genistein, thus gave an apparent EC50 of （40.4±6.8）μmol/L and （150.2±7.4） μtmol/L respectively. Preliminary study shows that the binding sites for capsaicin and dihydrocapsaicin may be probably partially overlapped with that for genistein because the maximal activation of wild-type CFTR with genistein is partially blocked by caosaicin and dihydrocapsaicin.
基金Supported by the Program for New Century Excellent Talents in University of China(No.NCET-07-0406)the Program for Excellent Talents in University of Liaoning Province,China(No.2006R33)+1 种基金Changchun Municipal Science and Technology Fund (No.2007sf19)Project of General Administration of Quality Supervision of China(No.2006IK145)
文摘Theophylline has been widely used in the＇treatment of airway disease but molecular mechanism has not been clearly elucidated. Previous studies have manifested that theophylline increases intracellular cAMP concentra- tion. Because cystic fibrosis transmembrane conductance regulator（CFTR） is a cAMP-dependent Cl- channel that plays key roles in fluid secretion in vivo, we postulated that theophylline activates CFTR channel gating. We found （1） theophylline stimulated CFTR-mediated anion transport in a concentration-dependent manner, and CFTR specific blocker completely reversed the effect; （2） theophylline had no effect on △F508 or G551D mutant CFTR chloride channel activity; （3） theophylline had additive effect with forskolin（FSK） and 3-isobutyl-xanthin（IBMX）, thus a direct binding activation mechanism was suggested. In conclusion, the results may provide a clue to elucidating the molecular mechanism of theophylline activities and theophylline may present a novel lead drug in treating CFTR-related disease.
基金supported by the National Natural Science Foundation of China(Grant No.30770276).
文摘Recent studies on the inhibition of tumor growth by Se-containing polysaccharide were reviewed.Meanwhile,the possible molecular mechanisms of the inhibition of tumor cell growth through antioxidation,induction of tumor cell apoptosis,blockade of cell cycle,and enhancement of immunity by Se-containing polysaccharide were proposed.In the end,the potential application of Se-containing polysaccharide in the prevention and treatment of tumor was elucidated.
