A novel marine active polypeptide （PCF）, isolated from the gonochoric Chinese scallop, Chlamys farreri, has potential antioxidant and anti-apoptotic activity against ultraviolet irradiation. We investigated whether ...A novel marine active polypeptide （PCF）, isolated from the gonochoric Chinese scallop, Chlamys farreri, has potential antioxidant and anti-apoptotic activity against ultraviolet irradiation. We investigated whether UVB-induced HaCaT cell apoptosis occurs via the mitochondrial pathways Apaf-1/caspase-9 and Smac/XIAP/caspase-3. We then investigated the molecular mechanisms controlling the anti-apoptotic effect of PCE Pre-treatment with PCF and caspase-9 inhibitor significantly inhibited UVB-induced apoptosis in HaCaT cells based on a DNA fragmentation assay and Hoechst 33258 staining The expression of Apaf-1 and the cleavage of procaspase-9 were dose-dependently reduced by 1.42-5.96 mmol/L PCF pretreatment in UVB-irradiated HaCaT cells. This was followed by inhibition of cleavage of procaspase-3, whose activation induced cell apoptosis. Meanwhile, PCF significantly and dose-dependently enhanced the activation of ATPase. Furthermore, we demonstrated that PCF strongly inhibited the release of Smac from the mitochondria to cytosol by reducing the degradation of XIAP dose-dependently. We conclude that the protective effect of PCF against UVB irradiation in HaCaT cells may be attributed to the inhibition of the Apaf-1/caspase-9 and Smac/XIAP/caspase-3 apoptotic signaling pathways.展开更多
目的:检测凋亡蛋白酶活化因子-1(Apaf-1)、细胞凋亡蛋白酶-9(Caspase-9)和Bcl-2相关X蛋白(Bcl-2-associated X protein,Bax)在基底细胞样乳腺癌(BLBC)中的表达,分析Apaf-1、Caspase-9和Bax与BLBC临床病理特征的关系。方法:采用免疫组化...目的:检测凋亡蛋白酶活化因子-1(Apaf-1)、细胞凋亡蛋白酶-9(Caspase-9)和Bcl-2相关X蛋白(Bcl-2-associated X protein,Bax)在基底细胞样乳腺癌(BLBC)中的表达,分析Apaf-1、Caspase-9和Bax与BLBC临床病理特征的关系。方法:采用免疫组化方法检测43例基底细胞样乳腺癌(BLBC)、57例non-BLBC(非基底细胞样乳腺癌)和60例癌旁正常乳腺组织中Apaf-1、Caspase-9和Bax蛋白的表达。结果 :免疫组化检测结果显示,BLBC及non-BLBC中Apaf-1、Caspase-9和Bax的表达水平都明显低于癌旁正常乳腺组织,差异均有统计学意义(P<0.05);Apaf-1在BLBC中的表达率与患者年龄无关,与肿瘤大小、淋巴结转移情况及临床分期相关,Caspase-9和Bax的表达水平和患者年龄及肿瘤大小无关,与BLBC淋巴结转移及临床分期相关(P<0.05)。结论:BLBC组织低表达Apaf-1、Caspase-9和Bax,三者表达分别呈正相关(P<0.01),Apaf-1、Caspase-9和Bax可能与BLBC的发生、发展密切相关。展开更多
基金Supported by the National Natural Science Foundation of China (No 30471458)the Natural Science Foundation of Shandong Province,China (No Z2007c09)
文摘A novel marine active polypeptide （PCF）, isolated from the gonochoric Chinese scallop, Chlamys farreri, has potential antioxidant and anti-apoptotic activity against ultraviolet irradiation. We investigated whether UVB-induced HaCaT cell apoptosis occurs via the mitochondrial pathways Apaf-1/caspase-9 and Smac/XIAP/caspase-3. We then investigated the molecular mechanisms controlling the anti-apoptotic effect of PCE Pre-treatment with PCF and caspase-9 inhibitor significantly inhibited UVB-induced apoptosis in HaCaT cells based on a DNA fragmentation assay and Hoechst 33258 staining The expression of Apaf-1 and the cleavage of procaspase-9 were dose-dependently reduced by 1.42-5.96 mmol/L PCF pretreatment in UVB-irradiated HaCaT cells. This was followed by inhibition of cleavage of procaspase-3, whose activation induced cell apoptosis. Meanwhile, PCF significantly and dose-dependently enhanced the activation of ATPase. Furthermore, we demonstrated that PCF strongly inhibited the release of Smac from the mitochondria to cytosol by reducing the degradation of XIAP dose-dependently. We conclude that the protective effect of PCF against UVB irradiation in HaCaT cells may be attributed to the inhibition of the Apaf-1/caspase-9 and Smac/XIAP/caspase-3 apoptotic signaling pathways.
文摘目的:检测凋亡蛋白酶活化因子-1(Apaf-1)、细胞凋亡蛋白酶-9(Caspase-9)和Bcl-2相关X蛋白(Bcl-2-associated X protein,Bax)在基底细胞样乳腺癌(BLBC)中的表达,分析Apaf-1、Caspase-9和Bax与BLBC临床病理特征的关系。方法:采用免疫组化方法检测43例基底细胞样乳腺癌(BLBC)、57例non-BLBC(非基底细胞样乳腺癌)和60例癌旁正常乳腺组织中Apaf-1、Caspase-9和Bax蛋白的表达。结果 :免疫组化检测结果显示,BLBC及non-BLBC中Apaf-1、Caspase-9和Bax的表达水平都明显低于癌旁正常乳腺组织,差异均有统计学意义(P<0.05);Apaf-1在BLBC中的表达率与患者年龄无关,与肿瘤大小、淋巴结转移情况及临床分期相关,Caspase-9和Bax的表达水平和患者年龄及肿瘤大小无关,与BLBC淋巴结转移及临床分期相关(P<0.05)。结论:BLBC组织低表达Apaf-1、Caspase-9和Bax,三者表达分别呈正相关(P<0.01),Apaf-1、Caspase-9和Bax可能与BLBC的发生、发展密切相关。
