AIM： To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-y （PPART） ligand, on the development of acute pancreatitis （AP） and on the expression of heat shock protein 70 ...AIM： To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-y （PPART） ligand, on the development of acute pancreatitis （AP） and on the expression of heat shock protein 70 （HSP70） in the pancreas. METHODS： AP was induced in rats by subcutaneous infusion of ceruw was measured by laser Dopplein for 5 h. Pancreatic blood floler flowmetry. Plasma lipase activity, intedeukin-1β （IL-1β） and IL-10 were determined. Pancreatic weight and histology were evaluated and pancreatic DNA synthesis and blood flow as well as pancreatic mRNA for IL-1β and HSP70 were assessed in rats treated with pioglitazone alone or in combination with cerulein. RESULTS： Pioglitazone administered （10-100 mg/kg i.g.） 30 min before cerulein, attenuated dose-dependently the pancreatic tissue damage in cerulein-induced pancreatitis （tiP） as demonstrated by the improvement of pancreatic histology, reduction in plasma lipase activity, plasma concentration of pro-inflammatory IL-1β and its gene expression in the pancreas and attenuation of the pancreatitis-evoked fall in pancreatic blood flow. CIP increased pancreatic HSP70 mRNA and protein expression in the pancreas and this effect was enhanced by pioglitazone treatment. CONCLUSION： Pioglitazone attenuates CIP and the beneficial effect of this pioglitazone is multifactorial probably due to its anti-infiammatory activities, to the suppression of IL-1β and to the overexpression of HSP70. PPART ligands could represent a new therapeutic optionin the treatment of AP.展开更多
AIM： To investigate the effect of ceramide on the cell cycle in human hepatocarcinoma Bel7402 cells. Possible molecular mechanisms were explored. METHODS： [3- （4, 5）-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium ...AIM： To investigate the effect of ceramide on the cell cycle in human hepatocarcinoma Bel7402 cells. Possible molecular mechanisms were explored. METHODS： [3- （4, 5）-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide （MTT） assay, plasmid transfection, reporter assay, FACS and Western blotting analyses were employed to investigate the effect and the related molecular mechanisms of C2-ceramide on the cell cycle of Bel7402 cells. RESULTS： C2-ceramide was found to inhibit the growth of Bel7402 cells by indudng cell cycle arrest. During the process, the expression of p21 protein increased, while that of cyclinD1, phospho-ERKl/2 and c-myc decreased. Furthermore, the level of CDK7 was downregulated, while the transcriptional activity of PPARy was upregulated. Addition of GW9662, which is a PPARy specific antagonist, could reserve the modulation action on CDK7. CONCLUSION： Our results support the hypothesis that cell cycle arrest induced by C2-ceramide may be mediated via accumulation of p21 and reduction of cyclinD1 and CDK7, at least partly, through PPARy activation. The ERK signaling pathway was involved in this process.展开更多
Objective： To investigate the effect of activation of peroxisome proliferator-activated receptor gamma （PPARy） on cell cycle arrest of gastric carcinoma cell line MGC803. Methods： The inhibitory of pioglitazone （...Objective： To investigate the effect of activation of peroxisome proliferator-activated receptor gamma （PPARy） on cell cycle arrest of gastric carcinoma cell line MGC803. Methods： The inhibitory of pioglitazone （PGZ） on proliferation of MGC803 cells was analyzed by MTT assay. Cell cycle was detected by flow cytometry （FCM）. The expressions of PPARy, cyclin D1 and cell cycle protein-dependent kinase CDK4 in MGC803 cells were detected by reverse transcriptase-polymerase chain reaction （RT-PCR）. Results： Treatment with 0.1-10 μmol/L PGZ for 96 h significantly inhibited cell proliferation. The proportion of MGC803 cells at G1 phase was significantly increased when treated with 10 μmol/L PGZ for 48, 72 and 96 h, and showed an apparent G1 phase arrest. The expression of PPARy was at a low level in MGC803 cells and significantly up-regulated when treated with 10 μmol/L PGZ for 48 h （P〈0.01）. The expression of CDK4 in MGC803 cells was remarkably down-regulated when treated with 10 μmol/L PGZ for 48 h and the expression of cyclin D1 was slightly down-regulated （P 〈 0.01）. Conclusion： Activation of PPARy significantly induced G1 phase arrest, which was associated with down-regulation of the expressions of CDK4 and cyclin DI.展开更多
The present study was undertaken to evaluate the influence of the methanolic fruit extract of Momordica cymbalaria （MFMC） on PPARγ, （Peroxisome Proliferator Activated Receptor gamma） and GLUT-4 （Glucose transpor...The present study was undertaken to evaluate the influence of the methanolic fruit extract of Momordica cymbalaria （MFMC） on PPARγ, （Peroxisome Proliferator Activated Receptor gamma） and GLUT-4 （Glucose transporter-4） with respect to glucose transport. Various concentrations of MFMC ranging from 62.5 to 500 μg·mL^-1 were evaluated for glucose uptake activity in vitro using L6 myotubes, rosiglitazone was used as a reference standard. The MFMC showed significant and dose-dependent increase in glucose uptake at the tested concentrations, further, the glucose uptake activity of MFMC （500 μg·mL^-1） was comparable with rosigilitazone. Furthermore, MFMC has shown up-regulation of GLUT-4 and PPARy gene expressions in L6 myotubes. In addition, the MFMC when incubated along with cycloheximide （CHX）, which is a protein synthesis inhibitor, has shown complete blockade of glucose uptake. This indicates that new protein synthesis is required for increased GLUT-4 translocation. In conclusion, these findings suggest that MFMC is enhancing the glucose uptake significantly and dose dependently through the enhanced expression of PPARμ and GLUT-4 in vitro.展开更多
文摘AIM： To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-y （PPART） ligand, on the development of acute pancreatitis （AP） and on the expression of heat shock protein 70 （HSP70） in the pancreas. METHODS： AP was induced in rats by subcutaneous infusion of ceruw was measured by laser Dopplein for 5 h. Pancreatic blood floler flowmetry. Plasma lipase activity, intedeukin-1β （IL-1β） and IL-10 were determined. Pancreatic weight and histology were evaluated and pancreatic DNA synthesis and blood flow as well as pancreatic mRNA for IL-1β and HSP70 were assessed in rats treated with pioglitazone alone or in combination with cerulein. RESULTS： Pioglitazone administered （10-100 mg/kg i.g.） 30 min before cerulein, attenuated dose-dependently the pancreatic tissue damage in cerulein-induced pancreatitis （tiP） as demonstrated by the improvement of pancreatic histology, reduction in plasma lipase activity, plasma concentration of pro-inflammatory IL-1β and its gene expression in the pancreas and attenuation of the pancreatitis-evoked fall in pancreatic blood flow. CIP increased pancreatic HSP70 mRNA and protein expression in the pancreas and this effect was enhanced by pioglitazone treatment. CONCLUSION： Pioglitazone attenuates CIP and the beneficial effect of this pioglitazone is multifactorial probably due to its anti-infiammatory activities, to the suppression of IL-1β and to the overexpression of HSP70. PPART ligands could represent a new therapeutic optionin the treatment of AP.
文摘AIM： To investigate the effect of ceramide on the cell cycle in human hepatocarcinoma Bel7402 cells. Possible molecular mechanisms were explored. METHODS： [3- （4, 5）-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide （MTT） assay, plasmid transfection, reporter assay, FACS and Western blotting analyses were employed to investigate the effect and the related molecular mechanisms of C2-ceramide on the cell cycle of Bel7402 cells. RESULTS： C2-ceramide was found to inhibit the growth of Bel7402 cells by indudng cell cycle arrest. During the process, the expression of p21 protein increased, while that of cyclinD1, phospho-ERKl/2 and c-myc decreased. Furthermore, the level of CDK7 was downregulated, while the transcriptional activity of PPARy was upregulated. Addition of GW9662, which is a PPARy specific antagonist, could reserve the modulation action on CDK7. CONCLUSION： Our results support the hypothesis that cell cycle arrest induced by C2-ceramide may be mediated via accumulation of p21 and reduction of cyclinD1 and CDK7, at least partly, through PPARy activation. The ERK signaling pathway was involved in this process.
文摘Objective： To investigate the effect of activation of peroxisome proliferator-activated receptor gamma （PPARy） on cell cycle arrest of gastric carcinoma cell line MGC803. Methods： The inhibitory of pioglitazone （PGZ） on proliferation of MGC803 cells was analyzed by MTT assay. Cell cycle was detected by flow cytometry （FCM）. The expressions of PPARy, cyclin D1 and cell cycle protein-dependent kinase CDK4 in MGC803 cells were detected by reverse transcriptase-polymerase chain reaction （RT-PCR）. Results： Treatment with 0.1-10 μmol/L PGZ for 96 h significantly inhibited cell proliferation. The proportion of MGC803 cells at G1 phase was significantly increased when treated with 10 μmol/L PGZ for 48, 72 and 96 h, and showed an apparent G1 phase arrest. The expression of PPARy was at a low level in MGC803 cells and significantly up-regulated when treated with 10 μmol/L PGZ for 48 h （P〈0.01）. The expression of CDK4 in MGC803 cells was remarkably down-regulated when treated with 10 μmol/L PGZ for 48 h and the expression of cyclin D1 was slightly down-regulated （P 〈 0.01）. Conclusion： Activation of PPARy significantly induced G1 phase arrest, which was associated with down-regulation of the expressions of CDK4 and cyclin DI.
基金supported by Padmashree Institute of Information Sciences,Bangalore
文摘The present study was undertaken to evaluate the influence of the methanolic fruit extract of Momordica cymbalaria （MFMC） on PPARγ, （Peroxisome Proliferator Activated Receptor gamma） and GLUT-4 （Glucose transporter-4） with respect to glucose transport. Various concentrations of MFMC ranging from 62.5 to 500 μg·mL^-1 were evaluated for glucose uptake activity in vitro using L6 myotubes, rosiglitazone was used as a reference standard. The MFMC showed significant and dose-dependent increase in glucose uptake at the tested concentrations, further, the glucose uptake activity of MFMC （500 μg·mL^-1） was comparable with rosigilitazone. Furthermore, MFMC has shown up-regulation of GLUT-4 and PPARy gene expressions in L6 myotubes. In addition, the MFMC when incubated along with cycloheximide （CHX）, which is a protein synthesis inhibitor, has shown complete blockade of glucose uptake. This indicates that new protein synthesis is required for increased GLUT-4 translocation. In conclusion, these findings suggest that MFMC is enhancing the glucose uptake significantly and dose dependently through the enhanced expression of PPARμ and GLUT-4 in vitro.
