MOMP in the absence of BH3-only proteins

The minimum requirement for mitochondrial apoptosis has been controversial ever since the discovery of BCL-2 as a cell death regulator. In this issue of Genes & Development, O''Neill and colleagues (pp. 973–988) end a long-standing debate by creating a cellular system free of BCL-2 family proteins, thereby identifying the outer mitochondrial membrane rather than BH3-only proteins as the only requirement for BAX/BAK activation and mitochondrial outer membrane permeabilization (MOMP).     

Cardioprotective effects of rutin in rats exposed to pirarubicin toxicity

We established both an acute and chronic cardiac toxicity rat model, which showed pretreatment with rutin attenuated pirarubicin-induced myocardial histopathological injury, electrocardiogram abnormalities, and cardiac dysfunction. Rutin also significantly reduced serum levels of MDA, BNP, CK-MB, CTnT, and LDH and increased serum SOD levels. Treatment with rutin and dexrazoxane resulted in an increase in Bcl-2/Bax ratio (p < 0.05) and reduction in JNK and Caspase-3 protein levels, compared to the pirarubicin group (all p < 0.05). Furthermore, rutin at a dose of 50 mg/kg significantly attenuated the above-mentioned alterations. Our study suggests the antioxidant and anti-apoptotic properties of rutin may be responsible for the cardioprotective effects observed.     

肺腺癌survivin表达与紫杉醇化疗疗效的关系

目的探讨抗凋亡蛋白survivin在肺腺癌组织中的表达及其与紫杉醇（PTX）化疗疗效的关系。方法应用免疫组化方法，对40例接受PTX化疗的肺腺癌患者survivin表达水平进行检测，分析其与PTX化疗疗效的关系。结果survivin在肺腺癌患者阳性率为65％（26／40）；survivin表达阳性率在化疗有效组（CR4例，PR6例）、稳定组（23例）、进展组（7例）分别为50．0％（5／10）、65．2％（15／23）、85．7％（6／7），有效组与进展组之间有显著性差异（P〈0．05）；survivin阳性组化疗有效率为12．0％（3／25），明显低：Fsurvivin表达阴性组46．7％（7／15）（P〈0．05）。结论survivin表达水平与PTX对肺腺癌化疗疗效呈显著负相关，survivin高表达者PTX化疗效果差，survivin可能作为一项预测PTX疗效、筛选肺腺癌化疗药物、指导制定合理治疗方案的新指标。     

强直性脊柱炎患者外周血T细胞凋亡及凋亡相关蛋白的表达

目的 探讨强直性脊柱炎患者外周血T细胞凋亡相关蛋白的表达以及T细胞凋亡状况,分析其在疾病免疫发病机制的作用.方法 CT检查患者骶髂关节并分级.尼龙棉柱法分离患者外周血T细胞,PI染色结合流式细胞术检测T细胞凋亡率.免疫组化法检测T细胞促凋亡蛋白FADD、Caspase-3、Caspase-8和抗凋亡蛋白FLIP表达.结果 与健康对照相比,强直性脊柱炎患者外周血T细胞凋亡率明显降低(P<0.05);促凋亡蛋白FADD、Caspase-3、Caspase-8百分率均明显降低(P<0.05),抗凋亡蛋白FLIP百分率明显升高(P<0.05).结论 强直性脊柱炎患者外周血T细胞凋亡蛋白及抗凋亡蛋白表达异常和T细胞凋亡不足与患者免疫学发病机制相关.     

白藜芦醇对乳腺癌MDA-MB-231细胞凋亡及Bcl-2蛋白表达的影响

目的探讨白藜芦醇(resveratrol,Res)对人乳腺癌MDA-MB-231细胞凋亡及相关蛋白Bcl-2表达的影响。方法不同浓度白藜芦醇处理人乳腺癌MDA-MB-231细胞,MTT法检测白藜芦醇对细胞增殖抑制率,流失细胞技术检测细胞凋亡,Western blot法检测细胞凋亡相关蛋白Bcl-2、Bcl-xl、Mcl-1和Caspase-3的表达。结果白藜芦醇25、50、100、200μmol/L处理细胞,增殖抑制率分别为(24.22±1.66)%、(30.79±1.60)%、(45.72±1.25)%和(53.31±1.94)%。白藜芦醇0、50、100、200μmol/L处理细胞,凋亡率分别为(3.53±0.25)%、(28.80±1.34)%、(38.78±1.19)%和(58.96±1.26)%。Western blot结果显示,白藜芦醇处理细胞后,Caspase-3蛋白裂解片段表达增加,凋亡相关蛋白Bcl-2和Bcl-xl的表达减低。结论白藜芦醇能诱导MDA-MB-231细胞凋亡增加,这可能与白藜芦醇激活Caspase-3蛋白同时抑制凋亡相关蛋白Bcl-2和Bcl-xl表达有关。     

颐和春口服液对肾阳虚大鼠肾损伤的保护作用

目的观察颐和春口服液对肾阳虚大鼠肾功能的保护作用,并初步探讨其机制。方法用腺嘌呤灌胃制备肾阳虚大鼠模型。实验分为正常对照组、肾阳虚模型组、肾阳虚阳性药物治疗组和肾阳虚颐和春治疗组。给药10d后观察颐和春口服液对肾阳虚大鼠体重、肾指数、肾功能及肾形态学改变,并从凋亡和抗氧化方面探讨其保护机制。HE染色观察肾形态学改变、生化法测定血清谷胱甘肽过氧化物酶（GSH-PX）、血尿素氮（BUN）和肌酐（Cr）,末端标记法测定肾组织凋亡。结果颐和春可改善肾阳虚引起的大鼠体重下降,使肾指数增加,降低血清肌酐（Cr）和尿素氮（BUN）水平,改善肾形态学表现,减轻肾小管上皮细胞凋亡,提高血清谷胱甘肽过氧化酶（GSH-PX）活性。结论颐和春口服液对肾阳虚大鼠肾功能有明显的保护作用,可能与提高抗凋亡和抗氧化能力有关。     

STI571/doxorubicin concentration-dependent switch for diverse caspase actions in CML cell line K562

We examined the response of the apoptosis-reluctant CML cell line K562 to doxorubicin alone or in combination with the tyrosine kinase inhibitor STI571. We found that at clinically relevant concentrations, doxorubicin induced differentiation and senescence, but did not induce apoptosis. Doxorubicin induced G(2)/M arrest and mitochondrial transmembrane potential dissipation. Interestingly, drug-induced differentiation could be diminished by caspase inhibitors. STI571 caused a graded response characterized by differentiation at low concentrations and apoptosis at higher. STI571 was not observed to induce senescence. Combination of STI571 and caspase inhibitors protected cells from apoptosis but did not influence differentiation. The diverse mode of action of both drugs contributed to the response observed during combination treatment. An additive effect on proliferation was obtained. The mechanisms contributing to inhibition of cellular proliferation were complex and strongly dependent on the applied drug concentrations. Differentiation or apoptosis were enhanced by combined treatment only in narrow ranges of concentrations. Conclusion: DOX and STI571 along diverse mechanisms contributed to elevated levels of activated caspases which might be then responsible for a switch from differentiation to apoptosis.     

Mcl-1小分子抑制剂在肿瘤治疗中的应用进展

目的阐述近年来Mcl-1小分子抑制剂的结构及在肿瘤治疗中的应用。方法归纳国内外的最新研究进展报道,按照分子结构类型,对主要的、具有发展潜力的重要分子抑制剂进行综述。结果采用计算机分子模拟、对接、活性预测,进一步通过毒性和活性测定,各种分子具有大小不等的抑制活性,并在肿瘤治疗中取得了较好的效果。结论 Mcl-1有望作为一种开发前景广阔的肿瘤治疗靶点。