目的:探讨核因子-κB(Nuclear factor kappa B,NF-κB)介导的促凋亡蛋白Bak(Bcl-2 associated K protein gene,Bak)及TNF-α的表达在溃疡性结肠炎(Ulcerative colitis,UC)发病中的作用机制。方法:选购80只清洁级SD大鼠,分为模型组和对...目的:探讨核因子-κB(Nuclear factor kappa B,NF-κB)介导的促凋亡蛋白Bak(Bcl-2 associated K protein gene,Bak)及TNF-α的表达在溃疡性结肠炎(Ulcerative colitis,UC)发病中的作用机制。方法:选购80只清洁级SD大鼠,分为模型组和对照组。UC大鼠模型制造采用"三硝基苯磺酸+乙醇"方法,模型制造成功后观察、评估结肠黏膜的大体形态及组织学变化。用免疫组织化学及RT-PCR法检测模型组与对照组中的NF-κB、Bak、TNF-α的表达水平,并分析相互之间关系。结果:UC大鼠模型制造成功率为97%。模型组固有层和黏膜层内炎性细胞浸润较对照组明显增多(P<0.01);NF-κB、TNF-α蛋白及mRNA表达水平模型组较对照组明显升高(P<0.01);Bak蛋白在模型组的炎细胞中表达明显低于对照组(P<0.01),而在结肠黏膜上皮细胞中的水平与对照组无明显差异(P>0.05)。NF-κB、TNF-α蛋白阳性细胞百分数及mRNA水平随模型组的组织学等级升高而增强,而Bak蛋白阳性细胞百分数是减弱的(P<0.05);且模型组中NF-κB与Bak蛋白的表达水平呈负相关(r=-0.793,P<0.01),NF-κB与TNF-α蛋白表达成正相关(r=0.892,P<0.01)。结论:NF-κB介导的促凋亡蛋白Bak的表达参与了UC的发生、发展。展开更多
Objective To analyze complications associated with posterior lumbar interbody fusion (PLIF) in which two Bagby and Kuslich (BAK) interbody fusion cages were implanted.Methods A total of 118 patients with spondylolyt...Objective To analyze complications associated with posterior lumbar interbody fusion (PLIF) in which two Bagby and Kuslich (BAK) interbody fusion cages were implanted.Methods A total of 118 patients with spondylolytic spondylolisthesis underwent single-level PLIF using two BAK cages filled with morselized autogenous bone. The major clinical and radiographic complications were analyzed after a follow-up with an average time of 2 years and 9 months.Results Complications were divided into intraoperative and postoperative complications. Intraoperative complications mainly included dural tear (4 patients, 3.4%), nerve root injury (3 patients, 2.5%) and suboptimal cage position (9 patients, 7.5%). No death was caused by the operation. Postoperative complications chiefly consisted of cage retropulsion (3 patients, 2.5%), cage subsidence (4 patients, 3.4%), and postlaminectomy arachnoiditis (2 patients, 1.7%). Pseudarthrosis was noted radiographically with evidence of motion between adjacent vertebra on lateral flexion-extension films and luciencies around the cages (2 patient, 1.7%), continuous posterior cage migration (2 patients, 1.7%) or continuous cage subsidence (2 patients, 1.7%). Two patients died, one from a traffic accident and the other from metastatic cancer 1 year postoperatively.Conclusions The results of this study indicate that PLIF with BAK cages is an effective but also technically difficult procedure. The relatively high incidence of complications reminds us of the importance of surgical indications and proper manipulations.展开更多
p53＇s apoptotic program consists of transcription-dependent and transcription-independent pathways. In the latter, physical interactions between mitochondrial p53 and anti- and pro-apoptotic members of the Bcl2 famil...p53＇s apoptotic program consists of transcription-dependent and transcription-independent pathways. In the latter, physical interactions between mitochondrial p53 and anti- and pro-apoptotic members of the Bcl2 family of mitochondrial permeability regulators are central. Using isogenic cell systems with defined deficiencies, we characterize in detail how mitochondrial p53 contributes to mitochondrial permeabilization, to what extent its action depends on other key Bcl2 family members and define its release activity. We show that mitochondrial p53 is highly efficient in inducing the release of soluble and insoluble apoptogenic factors by severely disrupting outer and inner mitochondrial membrane integrity. This action is associated with wild-type p53-induced oligomerization of Bax, Bak and VDAC and the formation of a stress-induced endogenous complex between p53 and cyclophilin D, normally located at the inner membrane. Tumor-derived p53 mutants are deficient in activating the Bax/Bak lipid pore. These actions are independent of Puma and Bax. Importantly, the latter distinguishes the mitochondrial from the cytosolic p53 death pathway.展开更多
Bcl-2家族蛋白质在细胞凋亡过程中起着重要的调控作用,Bax(Bcl-2-associated X proten)和Bak(Bcl-2 homologous antago-nist/killer)作为该家族中多结构域促凋亡蛋白,是线粒体外膜通透性改变的关键蛋白质,其发生的一系列分子事件在凋亡...Bcl-2家族蛋白质在细胞凋亡过程中起着重要的调控作用,Bax(Bcl-2-associated X proten)和Bak(Bcl-2 homologous antago-nist/killer)作为该家族中多结构域促凋亡蛋白,是线粒体外膜通透性改变的关键蛋白质,其发生的一系列分子事件在凋亡通路中发挥着重要的作用。目前对其作用的具体机制提出了两种主要的激活模型,即直接激活模型和间接激活模型。本文主要介绍Bax和Bak在接受凋亡信号后的激活与构象变化,并详细闸述了它们在凋亡通路中的激活模型。展开更多
文摘目的:探讨核因子-κB(Nuclear factor kappa B,NF-κB)介导的促凋亡蛋白Bak(Bcl-2 associated K protein gene,Bak)及TNF-α的表达在溃疡性结肠炎(Ulcerative colitis,UC)发病中的作用机制。方法:选购80只清洁级SD大鼠,分为模型组和对照组。UC大鼠模型制造采用"三硝基苯磺酸+乙醇"方法,模型制造成功后观察、评估结肠黏膜的大体形态及组织学变化。用免疫组织化学及RT-PCR法检测模型组与对照组中的NF-κB、Bak、TNF-α的表达水平,并分析相互之间关系。结果:UC大鼠模型制造成功率为97%。模型组固有层和黏膜层内炎性细胞浸润较对照组明显增多(P<0.01);NF-κB、TNF-α蛋白及mRNA表达水平模型组较对照组明显升高(P<0.01);Bak蛋白在模型组的炎细胞中表达明显低于对照组(P<0.01),而在结肠黏膜上皮细胞中的水平与对照组无明显差异(P>0.05)。NF-κB、TNF-α蛋白阳性细胞百分数及mRNA水平随模型组的组织学等级升高而增强,而Bak蛋白阳性细胞百分数是减弱的(P<0.05);且模型组中NF-κB与Bak蛋白的表达水平呈负相关(r=-0.793,P<0.01),NF-κB与TNF-α蛋白表达成正相关(r=0.892,P<0.01)。结论:NF-κB介导的促凋亡蛋白Bak的表达参与了UC的发生、发展。
文摘Objective To analyze complications associated with posterior lumbar interbody fusion (PLIF) in which two Bagby and Kuslich (BAK) interbody fusion cages were implanted.Methods A total of 118 patients with spondylolytic spondylolisthesis underwent single-level PLIF using two BAK cages filled with morselized autogenous bone. The major clinical and radiographic complications were analyzed after a follow-up with an average time of 2 years and 9 months.Results Complications were divided into intraoperative and postoperative complications. Intraoperative complications mainly included dural tear (4 patients, 3.4%), nerve root injury (3 patients, 2.5%) and suboptimal cage position (9 patients, 7.5%). No death was caused by the operation. Postoperative complications chiefly consisted of cage retropulsion (3 patients, 2.5%), cage subsidence (4 patients, 3.4%), and postlaminectomy arachnoiditis (2 patients, 1.7%). Pseudarthrosis was noted radiographically with evidence of motion between adjacent vertebra on lateral flexion-extension films and luciencies around the cages (2 patient, 1.7%), continuous posterior cage migration (2 patients, 1.7%) or continuous cage subsidence (2 patients, 1.7%). Two patients died, one from a traffic accident and the other from metastatic cancer 1 year postoperatively.Conclusions The results of this study indicate that PLIF with BAK cages is an effective but also technically difficult procedure. The relatively high incidence of complications reminds us of the importance of surgical indications and proper manipulations.
文摘p53＇s apoptotic program consists of transcription-dependent and transcription-independent pathways. In the latter, physical interactions between mitochondrial p53 and anti- and pro-apoptotic members of the Bcl2 family of mitochondrial permeability regulators are central. Using isogenic cell systems with defined deficiencies, we characterize in detail how mitochondrial p53 contributes to mitochondrial permeabilization, to what extent its action depends on other key Bcl2 family members and define its release activity. We show that mitochondrial p53 is highly efficient in inducing the release of soluble and insoluble apoptogenic factors by severely disrupting outer and inner mitochondrial membrane integrity. This action is associated with wild-type p53-induced oligomerization of Bax, Bak and VDAC and the formation of a stress-induced endogenous complex between p53 and cyclophilin D, normally located at the inner membrane. Tumor-derived p53 mutants are deficient in activating the Bax/Bak lipid pore. These actions are independent of Puma and Bax. Importantly, the latter distinguishes the mitochondrial from the cytosolic p53 death pathway.
文摘Bcl-2家族蛋白质在细胞凋亡过程中起着重要的调控作用,Bax(Bcl-2-associated X proten)和Bak(Bcl-2 homologous antago-nist/killer)作为该家族中多结构域促凋亡蛋白,是线粒体外膜通透性改变的关键蛋白质,其发生的一系列分子事件在凋亡通路中发挥着重要的作用。目前对其作用的具体机制提出了两种主要的激活模型,即直接激活模型和间接激活模型。本文主要介绍Bax和Bak在接受凋亡信号后的激活与构象变化,并详细闸述了它们在凋亡通路中的激活模型。
