Brain-derived neurotrophic factor was utilized in the present study to treat cell injury models induced by aggregated β-amyloid（25 35）. Methylthiazolyldiphenyl-tetrazolium bromide assay and western blot analysis sh...Brain-derived neurotrophic factor was utilized in the present study to treat cell injury models induced by aggregated β-amyloid（25 35）. Methylthiazolyldiphenyl-tetrazolium bromide assay and western blot analysis showed that brain-derived neurotrophic factor provided neuroprotection against cellular apoptosis by suppressing the decline in β-amyloid（25 35）-induced cell activity and the increasing ratio of Bax/Bcl-2. After treating pheochromocytoma cells with tyrosine kinase receptor B receptor inhibitor K252a, brain-derived neurotrophic factor reverses the above- mentioned changes. The experimental findings suggested that brain-derived neurotrophic factor prevented β-amyloid peptide-induced cellular apoptosis by modulating Bax/Bcl-2 expression, and this effect was associated with binding to the specific tyrosine kinase receptor B receptor.展开更多
OBJECTIVE To investigate whether nimesulide can suppress tumor growth and induce apoptosis in SGC-7901 gastric cancer cells and to explore the molecular mechanism involved. METHODS SGC-7901 cells were cultured in RPMI...OBJECTIVE To investigate whether nimesulide can suppress tumor growth and induce apoptosis in SGC-7901 gastric cancer cells and to explore the molecular mechanism involved. METHODS SGC-7901 cells were cultured in RPMI 1640 medium containing different concentrations of nimesulide （0,12.5, 50, 100, 200, 400 μmol/L）. The MTT assay, morphological observation, electron microscopy （EM）, immunohistochemical analysis and Western blot analysis were employed to investigate the effects of nimesulide on the SGC-7901 cells and to explore possible related molecular mechanisms. RESULTS Nimesulide inhibited the growth of SGC-7901 cells and elicited typical apoptotic morphologic changes. Nimesulide also decreased NF-κB and Bcl-2 expression, but increased the level of the Bax protein. The positive rate of Bcl-2 protein expression at 0, 50, 100 and 200 μmol/L of nimesulide was 58.3±14.0%, 50.2±9.9%, 32.8±5.0% and 22.7±5.5% respectively based on immunohistochemical staining. The positive rate of Bax protein expression was 22.0±5.7%, 29.2±6.5%, 42.7±5.9% and 74.5±9.1% and the NF-κB expression was 74.2±10.9%, 61.8±7.6%, 36.7±10.9% and 17.5±12.3%, Significant differences were found between so μmol/L and 100 μmol/L and 200μmol/L. Western blot analysis also showed that the expression of NF-κB was decreased. CONCLUSION Nimesulide suppresses tumor growth and induces apoptosis by inhibiting NF-κB expression, which may be related to the overexpression of Bax relative to Bcl-2 expression.展开更多
Objectives To administrated proteasome inhibitor-MG-132 prior to reperfusion in rat myocardial ischemia-reperfusion model to determine whether MG-132 could reduce myocytic apoptosis. Methods and results MG-132 （0. ...Objectives To administrated proteasome inhibitor-MG-132 prior to reperfusion in rat myocardial ischemia-reperfusion model to determine whether MG-132 could reduce myocytic apoptosis. Methods and results MG-132 （0. 75 mg/kg in 2 ml DMSO） injection 5 min prior to reperfusion resulted significant reduction of myocardial reperfusion injury. This effect was accompanied by reduced polymorphonuclear neutrophils （PMN） infiltration in myocardial region surrounding the myocardial infarct, reduced apoptosis in cardiac myocytes, reduced NF-κB activation, as determined by electron microscopy, histology, immunohistochemistry, the terminal deoxynucleotidyl transferase-mediated nick endlabeling （TUNEL） method, reverse transcription-polymerase chain reaction. Functional effects of MG-132 on PMN accumulation, activation of nuclear factor kappa B （p65 mRNA and protein levels ）, and apoptosis were characterized in rat myocardial tissue. MG132 time-dependently inhibited myocardial p65 mRNA expression and reduced myocardial apoptotic index （AI） after reperfusion for 2 h, 6 h and 24 h （ P 〈 0. 01 ）. Moreover, MG-132 time-dependently decreased Bax protein levels, while increased Bcl-2 protein levels in ischemic and reperfused myocardium （ P 〈 0. 05 ）, its effect peaked after reperfusion for 24 h. Conclusions Our results demonstrate that MG-132 reduced myocardial reperfusion injury by inhibiting myosytic apoptotic cell death and blocking activation of NF-κB, down-regulating Bax expression and up-regulating Bcl-2 expression as well as el evating Bcl-2/Bax ratio.展开更多
Objective： To explore the protective effect of sodium tanshinone ⅡA sulfonate （STS） on small intestine injury in rats with sepsis and its possible mechanism. Methods： According to a random number table, 24 Tats w...Objective： To explore the protective effect of sodium tanshinone ⅡA sulfonate （STS） on small intestine injury in rats with sepsis and its possible mechanism. Methods： According to a random number table, 24 Tats were randomly divided into 3 groups： sham operation group （sham group）, sepsis model group （model group） and STS treatment group （STS group）, with 8 Tats in each group. A rat model of sepsis was induced by cecal ligation and puncture （CLP） for 5 h. STS （1 mg/kg） was slowly injected through the right external jugular vein after CLP. The histopathologic changes in the intestine tissue were observed under a light microscope, and the intestinal epithelial cell apoptosis was evaluated by terminal deoxynucleoddyl transferase （TdT）-mediated dUTP nick-end labeling （TUNEL） method. The expressions of Bcl-2, Bax and nuclear factor κB （NF- κ B） p65 in the intestinal tissue was determined by Western blot. The levels of tumor necrosis factor α （TNF-α） and interleukin 6 （IL-6） in the intestinal tissue were determined using enzyme-linked immuno-sorbent assay （ELISA）. Results： Obvious injuries were observed in the intestinal tissue in the CLP group compared with the sham group. The expression of NF- K B p65 and the levels of TNF- α and IL-6 were up-regulated after CLP, the apoptosis of intestinal epithelial cells was increased after CLP, and the ratio of Bcl-2 to Bax was decreased. STS post- treatment could attenuate the injury on the intestinal tissue induced by CLP, decrease the apoptosis of intestinal epithelial cells and the levels of NF- κ B p65, TNF-α and IL-6, and increase the ratio of Bcl-2 to Bax. Conclusion： STS can protect the small intestine in rats with sepsis, and the mechanism may be associated with the inhibition of intestinal epithelial apoptosis and the reduction of activation of inflammatory cytokines.展开更多
文摘Brain-derived neurotrophic factor was utilized in the present study to treat cell injury models induced by aggregated β-amyloid（25 35）. Methylthiazolyldiphenyl-tetrazolium bromide assay and western blot analysis showed that brain-derived neurotrophic factor provided neuroprotection against cellular apoptosis by suppressing the decline in β-amyloid（25 35）-induced cell activity and the increasing ratio of Bax/Bcl-2. After treating pheochromocytoma cells with tyrosine kinase receptor B receptor inhibitor K252a, brain-derived neurotrophic factor reverses the above- mentioned changes. The experimental findings suggested that brain-derived neurotrophic factor prevented β-amyloid peptide-induced cellular apoptosis by modulating Bax/Bcl-2 expression, and this effect was associated with binding to the specific tyrosine kinase receptor B receptor.
基金This work was supported by the grant form the Natural Science Foundation of the Education Department of Jiangsu Province of China (No. 05KJD320234 and 01KJB320011).
文摘OBJECTIVE To investigate whether nimesulide can suppress tumor growth and induce apoptosis in SGC-7901 gastric cancer cells and to explore the molecular mechanism involved. METHODS SGC-7901 cells were cultured in RPMI 1640 medium containing different concentrations of nimesulide （0,12.5, 50, 100, 200, 400 μmol/L）. The MTT assay, morphological observation, electron microscopy （EM）, immunohistochemical analysis and Western blot analysis were employed to investigate the effects of nimesulide on the SGC-7901 cells and to explore possible related molecular mechanisms. RESULTS Nimesulide inhibited the growth of SGC-7901 cells and elicited typical apoptotic morphologic changes. Nimesulide also decreased NF-κB and Bcl-2 expression, but increased the level of the Bax protein. The positive rate of Bcl-2 protein expression at 0, 50, 100 and 200 μmol/L of nimesulide was 58.3±14.0%, 50.2±9.9%, 32.8±5.0% and 22.7±5.5% respectively based on immunohistochemical staining. The positive rate of Bax protein expression was 22.0±5.7%, 29.2±6.5%, 42.7±5.9% and 74.5±9.1% and the NF-κB expression was 74.2±10.9%, 61.8±7.6%, 36.7±10.9% and 17.5±12.3%, Significant differences were found between so μmol/L and 100 μmol/L and 200μmol/L. Western blot analysis also showed that the expression of NF-κB was decreased. CONCLUSION Nimesulide suppresses tumor growth and induces apoptosis by inhibiting NF-κB expression, which may be related to the overexpression of Bax relative to Bcl-2 expression.
文摘Objectives To administrated proteasome inhibitor-MG-132 prior to reperfusion in rat myocardial ischemia-reperfusion model to determine whether MG-132 could reduce myocytic apoptosis. Methods and results MG-132 （0. 75 mg/kg in 2 ml DMSO） injection 5 min prior to reperfusion resulted significant reduction of myocardial reperfusion injury. This effect was accompanied by reduced polymorphonuclear neutrophils （PMN） infiltration in myocardial region surrounding the myocardial infarct, reduced apoptosis in cardiac myocytes, reduced NF-κB activation, as determined by electron microscopy, histology, immunohistochemistry, the terminal deoxynucleotidyl transferase-mediated nick endlabeling （TUNEL） method, reverse transcription-polymerase chain reaction. Functional effects of MG-132 on PMN accumulation, activation of nuclear factor kappa B （p65 mRNA and protein levels ）, and apoptosis were characterized in rat myocardial tissue. MG132 time-dependently inhibited myocardial p65 mRNA expression and reduced myocardial apoptotic index （AI） after reperfusion for 2 h, 6 h and 24 h （ P 〈 0. 01 ）. Moreover, MG-132 time-dependently decreased Bax protein levels, while increased Bcl-2 protein levels in ischemic and reperfused myocardium （ P 〈 0. 05 ）, its effect peaked after reperfusion for 24 h. Conclusions Our results demonstrate that MG-132 reduced myocardial reperfusion injury by inhibiting myosytic apoptotic cell death and blocking activation of NF-κB, down-regulating Bax expression and up-regulating Bcl-2 expression as well as el evating Bcl-2/Bax ratio.
基金Supported by a Grant from Hubei Province Science and Technique Foundation(No.2009CDB371)
文摘Objective： To explore the protective effect of sodium tanshinone ⅡA sulfonate （STS） on small intestine injury in rats with sepsis and its possible mechanism. Methods： According to a random number table, 24 Tats were randomly divided into 3 groups： sham operation group （sham group）, sepsis model group （model group） and STS treatment group （STS group）, with 8 Tats in each group. A rat model of sepsis was induced by cecal ligation and puncture （CLP） for 5 h. STS （1 mg/kg） was slowly injected through the right external jugular vein after CLP. The histopathologic changes in the intestine tissue were observed under a light microscope, and the intestinal epithelial cell apoptosis was evaluated by terminal deoxynucleoddyl transferase （TdT）-mediated dUTP nick-end labeling （TUNEL） method. The expressions of Bcl-2, Bax and nuclear factor κB （NF- κ B） p65 in the intestinal tissue was determined by Western blot. The levels of tumor necrosis factor α （TNF-α） and interleukin 6 （IL-6） in the intestinal tissue were determined using enzyme-linked immuno-sorbent assay （ELISA）. Results： Obvious injuries were observed in the intestinal tissue in the CLP group compared with the sham group. The expression of NF- K B p65 and the levels of TNF- α and IL-6 were up-regulated after CLP, the apoptosis of intestinal epithelial cells was increased after CLP, and the ratio of Bcl-2 to Bax was decreased. STS post- treatment could attenuate the injury on the intestinal tissue induced by CLP, decrease the apoptosis of intestinal epithelial cells and the levels of NF- κ B p65, TNF-α and IL-6, and increase the ratio of Bcl-2 to Bax. Conclusion： STS can protect the small intestine in rats with sepsis, and the mechanism may be associated with the inhibition of intestinal epithelial apoptosis and the reduction of activation of inflammatory cytokines.
