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Signal transduction mediated by Bid,a pro-death Bcl-2 family proteins, connects the death receptor and mitochondria apoptosis pathways 被引量:25
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作者 YIN XIAO-MING (Department of Pathology, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15261, USA) 《Cell Research》 SCIE CAS CSCD 2000年第3期161-167,共7页
Two major apoptosis pathways have been defined in mammalian cells, the Fas/TNF-R1 death receptor pathway and the mitochondria pathway. The Bcl-2 family proteins consist of both anti-apoptosis and pro- apoptosis member... Two major apoptosis pathways have been defined in mammalian cells, the Fas/TNF-R1 death receptor pathway and the mitochondria pathway. The Bcl-2 family proteins consist of both anti-apoptosis and pro- apoptosis members that regulate apoptosis, mainly by controlling the release of cytochrome c and other mitochondrial apoptotic events. However, death signals mediated by Fas/TNF-R1 receptors can usually activate caspases directly, bypassing the need for mitochondria and escaping the regulation by Bcl-2 family proteins. Bid is a novel pro-apoptosis Bcl-2 family protein that is activated by caspase 8 in response to Fas/TNF-R1 death receptor signals. Activated Bid is translocated to mitochondria and induces cytochrome c release, which in turn activates downstream caspases. Such a connection between the two apoptosis pathways could be important for induction of apoptosis in certain types of cells and responsible for the pathogenesis of a number of human diseases. 展开更多
关键词 Apoptosis bcl-2 family proteins BID FAS TNF.
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Regulatory Effect of Bcl-2 Family Proteins in CPB-induced Cardiomyocyte Apoptosis in Dog Hearts 被引量:1
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作者 SUN Zongquan(孙宗全) +4 位作者 ZHANG Shunye(张顺业) LIU LIxin(刘立新) Hasichaolu(哈斯朝鲁) 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2002年第2期103-106,共4页
Summary: Whether conventional hypothermic CPB induces myocyte apoptosis in dog hearts and modulation of bcl-2, bcl-xl, bax, bad, and caspase-3 pathways in this setting was investigated. Ten healthy adult dogs were ra... Summary: Whether conventional hypothermic CPB induces myocyte apoptosis in dog hearts and modulation of bcl-2, bcl-xl, bax, bad, and caspase-3 pathways in this setting was investigated. Ten healthy adult dogs were randomized into sham-operated and CPB groups. Samples of left ventricle were obtained before, during and 3 h after CPB. In situ TUNEL was used to detect apoptotic myocytes. Immunohistochemistry and flow cytometry were employed for detection of expressions of bcl-2, bcl-xl, bax and bad proteins. Z-DEVD-AMC substrate cleavage and TBARS methods were used to measure the activity of caspase-3 and the content of lipid peroxide in LV myocardium, respectively. After CPB, the number of apoptotic myocytes in CPB group was significantly increased. The results of immunohistichemistry demonstrated that bcl-2, bcl-xl, bax and bad proteins were constitutionally present on the sarcolemma of the LV myocytes. FACS results showed that, after CPB, expressions of bax and bad in CPB group were significantly upregulated, while the expressions of bcl-2 and bcl-xl were not significantly changed in both groups. The activity of caspase-3 and the content of lipid peroxide in LV myocardium in CPB group were also significantly increased after CPB. The present study shows that there exists myocardiocyte apoptosis in dog hearts undergoing conventional hypothermic CPB and the myocyte apoptosis is initiated by ischemia and performed during reperfusion. Moreover, the CPB-induced myocyte apoptosis was associated with upregulation of expressions of bax and bad proteins, activation of caspase-3 and increase of oxidative stress. 展开更多
关键词 cardiopulmonary bypass APOPTOSIS CASPASE-3 bcl-2 family proteins oxidative stress
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Response of the Ginseng C_(2)H_(2)-Type Zinc Finger Protein Family PgZFPs Gene to Methyl Jasmonate Regulation
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作者 Yue Jiang Lingyu Liu +7 位作者 Kangyu Wang Mingzhu Zhao Ping Chen Jun Lei Yanfang Wang Meiping Zhang Yi Wang Guang Chen 《Phyton-International Journal of Experimental Botany》 SCIE 2024年第11期3055-3071,共17页
The main active components of ginseng are ginsenosides,which play significant roles in treating cardiovascular diseases,cancer,and providing antioxidant effects.Ginsenosides are primarily synthesized through the mevalo... The main active components of ginseng are ginsenosides,which play significant roles in treating cardiovascular diseases,cancer,and providing antioxidant effects.Ginsenosides are primarily synthesized through the mevalo-nate pathway and the methylerythritol phosphate pathway.Many key enzyme genes involved in this biosynthetic process have been cloned and validated,yet the regulatory functions of transcription factors remain unclear.The C_(2)H_(2)-type zincfinger protein family,one of the largest families of transcription factors,is crucial in plant growth and development,response to biotic and abiotic stresses,and regulation of secondary metabolism.This study,based on the ginseng transcriptome database from Jilin,conducted a correlation analysis between the expression levels of PgZFPs genes in the Jilin ginseng C_(2)H_(2)-type zincfinger protein family and ginsenoside content,a gen-ome-wide association study of PgZFPs,and co-expression analysis of PgZFPs with validated key enzyme genes.Ultimately,five candidate genes involved in ginsenoside biosynthesis were identified.The involvement of PgZFP27 and PgZFP-59-02 genes from the PgZFPs family in the biosynthesis of ginsenosides was validated through in vitro methyl jasmonate(MeJA)induction experiments.This result provides new genetic resources for the biosynthesis of ginsenosides. 展开更多
关键词 GINSENOSIDES C_(2)H_(2)-type zincfinger protein family MeJA induction functional study SIT SITIENS FLC FLACCA MVA Mevalonate MEP 2-C-methyl-D-erythritol 4-phosphate GWAS Genome-wide association studies HPLC High-performance liquid chromatography
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Dioscin-induced Apoptosis of Human LNCaP Prostate Carcinoma Cells through Activation of Caspase-3 and Modulation of Bcl-2 Protein Family 被引量:16
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作者 陈静 李辉敏 +2 位作者 张学农 熊朝梅 阮金兰 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2014年第1期125-130,共6页
Dioscin is a natural steroid saponin derived from several plants, showing potent anti-cancer effect against a variety of tumor cell lines. In the present study, we investigated the anti-cancer activity of dioscin agai... Dioscin is a natural steroid saponin derived from several plants, showing potent anti-cancer effect against a variety of tumor cell lines. In the present study, we investigated the anti-cancer activity of dioscin against human LNCaP cells, and evaluated the possible mechanism involved in its antineoplastic action. It was found that dioscin(1, 2 and 4 μmol/L) could significantly inhibit the viability of LNCaP cells in a time- and concentration-dependent manner. Flow cytometry revealed that the apoptosis rate was increased after treatment of LNCaP cells with dioscin for 24 h, indicating that apoptosis was an important mechanism by which dioscin inhibited cancer. Western blotting was employed to detect the expression of caspase-3, Bcl-2 and Bax in LNCaP cells. The expression of cleaved caspase-3 was significantly increased, and meanwhile procaspase-3 was markedly decreased. The expression of anti-apoptotic protein Bcl-2 was down-regulated, whereas the pro-apoptotic protein Bax was up-regulated. Moreover, the Bcl-2/Bax ratio was drastically decreased. These results suggested that dioscin possessed potential anti-tumor activity in human LNCaP cells through the apoptosis pathway, which might be associated with caspase-3 and Bcl-2 protein family. 展开更多
关键词 DIOSCIN LNCAP ANTI-TUMOR apoptosis pathway capsase-3 bcl-2 protein family
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Effects of Ethyl Pyruvate on Myocardial Apoptosis and Expression of Bcl-2 and Bax Proteins after Ischemia-reperfusion in Rats 被引量:26
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作者 郭家龙 张凯伦 +2 位作者 季艳梅 蒋雄刚 左顺庆 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2008年第3期281-283,共3页
In order to study the effects of ethyl pyruvate on cardiomyocyte apoptosis following ischemia/reperfusion (I/R) in vitro and the expression of Bcl-2 and Bax proteins, isolated rat hearts were perfused in a Langendor... In order to study the effects of ethyl pyruvate on cardiomyocyte apoptosis following ischemia/reperfusion (I/R) in vitro and the expression of Bcl-2 and Bax proteins, isolated rat hearts were perfused in a Langendorff model. Twenty-four rats were randomly divided into 3 groups (n=8 in each group): control group was perfused for 120 min. In the I/R group, after 30 min stabilization the injury was induced by 30 min global ischemia followed by 60 min reperfusion. Ethyl pyruvate (EP) group was set up with the same protocol as I/R group except that it was supplied with 2 mmol/L EP 15 rain before ischemia and throughout reperfusion. Myocardial malonaldehyde (MDA) content was measured. Myocardial apoptotic index (AI) was tested by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. The expression of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax in cardiac myocytes was detected by immunohistochemistry. As compared with control group, the content of MDA, myocardial AI and the expression of Bcl-2, Bax proteins were increased significantly in I/R group, but the content of MDA, myocardial AI and the expression of Bax protein were decreased obviously and the expression of Bcl-2 protein was up-regulated in EP group (P〈0.05). These results demonstrate that EP could inhibit apoptosis of cardiac myocytes possibly via alleviating oxidative stress, up-regulating Bcl-2 and down-regulating Bax proteins. 展开更多
关键词 ethyl pyruvate myocardial reperfusion injury APOPTOSIS bcl-2 protein Bax protein
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The Expression of Apoptosis-Related Genes Bcl-2 and Bax Protein and Apoptosis Positivity in Cervical Carcinoma during Irradiation
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作者 赵东利 石景森 +2 位作者 李明众 宋丽萍 王书文 《The Chinese-German Journal of Clinical Oncology》 CAS 2005年第2期105-107,共3页
To evaluate the apoptosis positivity, the expression of Bcl-2, bax proteinsin 30 patients with squamous cell cervix carcinoma before and after radiotherapy. Methods: By usingimmuno-histochemical and TDT-dUTP nick end ... To evaluate the apoptosis positivity, the expression of Bcl-2, bax proteinsin 30 patients with squamous cell cervix carcinoma before and after radiotherapy. Methods: By usingimmuno-histochemical and TDT-dUTP nick end labelling techniques, 30 cases of squamous cell cervicalcarcinoma were analyzed. Results: The apoptosis positivity before and after irradiation was 76.7%and 100% respectively, with the difference being significant (P 【 0.05); The positive rates of Bcl-2protein before and after irradiation were 73.3% and 46.7% respectively, with the difference beingsignificant (P 【 0.05); The positive rates of bax protein before and after irradiation were 86% and100% respectively, with the difference being significant (P 【 0.05). Conclusion: bax and Bcl-2protein play an important role in apoptosis induced by fractionated radiation therapy. Apoptosisinduced by irradiation is contributed to upregulation of bax protein or downregulation of Bcl-2protein. 展开更多
关键词 cervical carcinoma RADIOTHERAPY apoptosis positivity bcl-2 protein baxprotein
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新型Bcl-2小分子抑制剂的设计、合成与初步活性评价
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作者 王宇璇 杨灿 +2 位作者 苏明波 池岛乔 白海云 《沈阳药科大学学报》 CAS CSCD 2024年第7期889-899,913,共12页
目的设计并合成一系列新型Bcl-2小分子抑制剂,测试其对Bcl-2和Bcl-2 G101V(Bcl-2突变体)与BH3-only蛋白相互作用的抑制活性,初步探究其构效关系,为后续相关研究提供参考。方法以临床化合物BGB-11417为先导化合物,通过骨架跃迁等方法,设... 目的设计并合成一系列新型Bcl-2小分子抑制剂,测试其对Bcl-2和Bcl-2 G101V(Bcl-2突变体)与BH3-only蛋白相互作用的抑制活性,初步探究其构效关系,为后续相关研究提供参考。方法以临床化合物BGB-11417为先导化合物,通过骨架跃迁等方法,设计新型含螺环结构的Bcl-2小分子抑制剂。以苯甲醛为原料,通过取代、环化和偶联等反应合成目标化合物,并通过1H NMR和LC-MS进行结构确定。采用时间分辨荧光共振能量转移(TR-FRET)评价目标化合物对Bcl-2和Bcl-2 G101V(Bcl-2突变体)与BH3-only蛋白相互作用的抑制能力。结果共合成8个新型螺环Bcl-2小分子抑制剂,其中29a[IC_(50)(Bcl-2):0.8 nmol·L^(-1),IC_(50)(Bcl-2 G101V):55.41 nmol·L^(-1)],29d[IC_(50)(Bcl-2):0.27 nmol·L^(-1),IC_(50)(Bcl-2 G101V):18.65 nmol·L^(-1)]对Bcl-2和Bcl-2 G101V与BH3-only蛋白的相互作用有较好的抑制活性。结论建立了一种新型螺环Bcl-2小分子抑制剂合成方法,发现了对Bcl-2和Bcl-2 G101V(Bcl-2突变体)与BH3-only蛋白相互作用有较好抑制活性的新化合物,其中29d具有进一步研究的价值。 展开更多
关键词 细胞凋亡 bcl-2 家族 bcl-2 突变蛋白 小分子抑制剂 分子对接
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New tight junction protein 2 variant causing progressive familial intrahepatic cholestasis type 4 in adults: A case report 被引量:6
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作者 Chun-Shan Wei Naja Becher +3 位作者 Jenny Blechingberg Friis Peter Ott Ida Vogel Henning Grønbæk 《World Journal of Gastroenterology》 SCIE CAS 2020年第5期550-561,共12页
BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)encompasses a group of autosomal recessive disorders with high morbidity and mortality.Variants in the gene encoding tight junction protein-2(TJP2)have bee... BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)encompasses a group of autosomal recessive disorders with high morbidity and mortality.Variants in the gene encoding tight junction protein-2(TJP2)have been linked to PFIC type 4(PFIC4),which predominantly presents in childhood.However,there are only limited data from adults with TJP2-related PFIC4.We report a family with an autosomal recessive disorder with a novel variant in the TJP2 gene in adults with very variable expression of PFIC4.CASE SUMMARY The index patient presented at 19 years old with liver cirrhosis and variceal bleeding and was treated with endoscopic banding and beta-blockers.In 2018,he developed primary liver cancer that was treated with radiofrequency ablation followed by liver transplantation in 2019.Genetic testing revealed a novel homozygous TJP2 variant causing PFIC4(TJP2([NM_004817.3]:c.[3334C>T];[3334C>T])).The consanguineous family consists of the father and mother(both heterozygous)and their 12 children,of which five carry the variant in a homozygous state;however,these five siblings have highly variable expression of PFIC4.Two homozygous brothers had cirrhosis and portal hypertension at diagnosis at the ages of 19 and 36.Two other homozygous brothers,age 23 and 19,and the homozygous sister,age 21,have elevated liver enzymes but presently no cirrhosis,which may suggest an age-dependent penetrance.In addition,five sisters had severe and mild intrahepatic cholestasis of pregnancy and carry the TJP2 variant in a homozygous and heterozygous state,respectively.CONCLUSION This novel TJP2 variant is associated with PFIC4 causing severe liver disease with cirrhosis and primary liver cancer in adolescents/adults. 展开更多
关键词 Progressive familial intrahepatic cholestasis Tight junction protein 2 Genetic variants Liver cirrhosis Liver cancer Case report
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Influence of Tanshinone lla on heat shock protein 70,Bcl-2 and Bax expression in rats with spinal ischemia/reperfusion injury 被引量:9
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作者 Li Zhang Weidong Gan Guoyao An 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第36期2882-2888,共7页
Tanshinone lla is an effective monomer component of Danshen, which is a traditional Chinese medicine for activating blood circulation to dissipate blood stasis. Tanshinone Ila can effectively improve brain tissue isch... Tanshinone lla is an effective monomer component of Danshen, which is a traditional Chinese medicine for activating blood circulation to dissipate blood stasis. Tanshinone Ila can effectively improve brain tissue ischemia/hypoxia injury. The present study established a rat model of spinal cord ischemia/reperfusion injury and intraperitoneally injected Tanshinone lla, 0.5 hour prior to model establishment. Results showed that Tanshinone Ila promoted heat shock protein 70 and Bcl-2 protein expression, but inhibited Bax protein expression in the injured spinal cord after ischemia/reperfusion injury. Furthermore, Nissl staining indicated a reduction in nerve cell apoptosis and fewer pathological lesions in the presence of Tanshinone Ila, compared with positive control Danshen injection. 展开更多
关键词 Tanshinone Ila DANSHEN spinal ischemia/reperfusion injury heat shock protein 70 bcl-2 BAX cellapoptosis Chinese medicine neural regeneration
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Pretreatment with low-frequency repetitive transcranial magnetic stimulation may influence neuronal Bcl-2 and Fas protein expression in the CA1 region of the hippocampus: A possible anti-epilepsy mechanism in a lithium-pilocarpine-induced epileptic rat mod 被引量:2
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作者 Sha Ke Hongning Zhao +6 位作者 Xiaoming Wang Junqiang Zhang Fang Chen Yuanxu Wang Xiaoqiong Zhao Hui Huang Jianxiu Hu 《Neural Regeneration Research》 SCIE CAS CSCD 2010年第12期895-900,共6页
BAOKGROUND: Bcl-2 and Fas proteins are well known as anti-apoptotic and pro-apoptotic factors respectively. However, whether the anti-epileptic mechanism of low-frequency repetitive transcranial magnetic stimulation ... BAOKGROUND: Bcl-2 and Fas proteins are well known as anti-apoptotic and pro-apoptotic factors respectively. However, whether the anti-epileptic mechanism of low-frequency repetitive transcranial magnetic stimulation (rTMS) involves an anti-apoptotic effect via regulating Bcl-2 and Fas protein expression remains to be determined. OBJECTIVE: To verify the correlation between the anti-epileptic mechanism following pretreatment of low-frequency rTMS and anti-hippocampal apoptosis. DESIGN, TIME AND SETTING: A randomized controlled animal experiment was performed at Institute of Neurological Disorders, Affiliated Hospital of North Sichuan Medical College between September 2007 and March 2008. MATERIALS: Pilocarpine (053K13011) was provided by Sigma, USA; lithium was provided by Shanghai Biotechnology Co., Ltd., China; Dantec Maglite-r25 rTMS instrument was provided by Dundee, Denmark. METHODS: A total of 21 adult male Wistar rats were randomly divided into control (n = 6), rTMS pretreatment (n = 9), and sham-stimulation (n = 6) groups. The rTMS pretreatment group was pretreated with low-frequency rTMS (0.5 Hz, 75% threshold intensity, 20 times/bundle, and 5 bundles/day), while the sham-stimulation group was sham-stimulated with a similar sound for 7 successive days to establish lithium-pilocarpine-induced epileptic state models. MAIN OUTCOME MEASURES: Epileptic stroke latency; neuronal morphology was observed using hematoxylin and eosin staining; mean positive-reactive cell number and mean absorbance of Bcl-2 and Fas protein in the hippocampal CA1 region was observed using immunohistochemistry. RESULTS: Epileptic latency in the rTMS pretreatment group was significantly enhanced (P 〈 0.01), and a number of degenerated neurons were observed to be apoptotic. Bcl-2 protein expression increased at each time point, but Fas protein expression decreased (P 〈 0.01). CONCLUSION: Low-frequency rTMS has an anti-epileptic effect, which may be via regulation of Bcl-2 and Fas protein expression in the hippocampal region. 展开更多
关键词 transcranial magnetic stimulation epileptic state bcl-2 protein Fas protein brain injury neural regeneration
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THE EXPERIMENTAL STUDY ON THE CELL APOPTOSIS AND EXPRESSION OF BCL-2 PROTEIN IN INTRACEREBRAL HEMORRHAGE IN MODEL OF RATS 被引量:2
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作者 鲍刚 郭宁 +2 位作者 张仲林 陈伟 鲍得虎 《Journal of Pharmaceutical Analysis》 SCIE CAS 2006年第1期61-64,共4页
Objective To study whether there is the apoptosis of neural cells and the expression of Bcl-2 protein in intracerebral hemorrhage (ICH) in model of rats, for the further understanding the mechanism of the delayed dama... Objective To study whether there is the apoptosis of neural cells and the expression of Bcl-2 protein in intracerebral hemorrhage (ICH) in model of rats, for the further understanding the mechanism of the delayed damage of the neural cells around the hematoma after ICH. Methods Fifty SD rats were randomly divided into 5 groups, ten in each. With the Group A as the control, the rest 40 were used to set up intracerebral hemorrhage model. The brains were taken out at 12 th , 24 th , 48 th and 72 th hours, respectively. Apoptosis cells were detected with terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL), and the expression of Bcl-2 protein was detected with immunochemical stainging methed (SP). Results In the control group, no apoptosis cells and Bc1-2 protein were detected. In rest groups, the apoptosis cells and Bc1-2 protein were expressed in different degree. Apoptosis rates verified and corresponded with the time after ICH, with the peak at 48 th -72 th hour after hemorrhage. The peak rate of apoptosis cells was (24.50±2.69)% and Bcl-2 protein expression was (20.76±1.97)% . There was significant difference between the experimental groups and control (P<0.05), and no linear relationship between the apoptosis rate and the expression of Bcl-2 protein. Conclusion Apoptosis may be an important factor in the secondary trauma of ICH. There is a time leg after hemorrhage. All this is instructive to clinical treatment in time. Bcl-2 protein keeps increasing in a certain time after hemorrhage, but not synchronize with the cell apoptosis. This indicates that bcl-2 has the effect to reduce the apoptosis of neural cells. 展开更多
关键词 APOPTOSIS intracerebral hemorrhage bcl-2 protein RAT
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PRRT2基因突变相关疾病谱的临床特征及遗传学分析
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作者 王诗雨 唐蒙蒙 +5 位作者 刘辉 张田田 陈润泽 朱小颖 贾宇 张礼萍 《中国实用神经疾病杂志》 2025年第1期1-6,共6页
目的回顾性分析总结10例PRRT2基因突变相关疾病谱患者的临床特点及遗传学特征。方法收集2020-07—2022-08就诊于首都医科大学宣武医院儿科的10例PRRT2基因相关癫痫患儿的临床特征、脑电图、头颅磁共振检查、基因特征及治疗结果,回顾性... 目的回顾性分析总结10例PRRT2基因突变相关疾病谱患者的临床特点及遗传学特征。方法收集2020-07—2022-08就诊于首都医科大学宣武医院儿科的10例PRRT2基因相关癫痫患儿的临床特征、脑电图、头颅磁共振检查、基因特征及治疗结果,回顾性分析其特征。结果10例患儿均提示PRRT2基因杂合突变,其中3例为片段缺失,5例为移码突变,1例为剪接突变。10例患者中男5例,女5例,起病年龄4个月~10岁,其中7例诊断为自限性家族性婴儿癫痫(SFIE),1例诊断为发作性运动诱发性运动障碍(PKD),2例诊断为伴婴儿惊厥的发作性运动诱发性运动障碍(IC/PKD);5例存在PRRT2基因突变相关疾病家族史。7例口服奥卡西平治疗后发作控制,3例口服左乙拉西坦治疗后发作控制。结论PKD、SFIE及IC/PKD是一组与PRRT2基因突变相关的疾病谱,c.649dupC基因突变位点是热点突变位点。对于高度考虑SFIE、PKD及IC/PKD的患者,如全外显子测序未发现异常基因,需进一步行内含子及染色体微缺失/微重复检测,达到早期诊断及治疗的目的。 展开更多
关键词 富含脯氨酸的跨膜蛋白2 PRRT2基因突变相关疾病谱 发作性运动诱发性运动障碍 自限性家族性婴儿癫痫 伴婴儿惊厥的发作性运动诱发性运动障碍 临床特点 遗传学特征
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THE QUANTITATIVE MEASUREMENT OF BCL-2, P53 PROTEIN AND PCNA EXPRESSION IN BREAST CARCINOMA AND THEIR CORRELATION WITH PROGNOSIS
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作者 张学斌 王鸿雁 《Journal of Pharmaceutical Analysis》 CAS 1998年第2期120-124,132,共6页
To study quantitative index of bci-2, P53, Nroliferating cell nuclear antigen (PCNA),ER and PR in breast carcinoma and their correiation and their relatiousbip with prognosis, the ex expression of bcl-2, P53 and PCNA ... To study quantitative index of bci-2, P53, Nroliferating cell nuclear antigen (PCNA),ER and PR in breast carcinoma and their correiation and their relatiousbip with prognosis, the ex expression of bcl-2, P53 and PCNA were studied by immunohistochemical technique. The measurementof ER and PR used enzyme linked affinuity histochemical methods. The quantitative index was analyzed by image technique. All analyses were hased on 60 breast carcinomas. The results were as follows:the more bcl-2 protein, the lower histological graded the longer survival term and the highersurvival rate (P< 0. 05). The quautitative measurement of bcl-2, P53 and PCNA expression were ofvalue in evaluating the degree of differentiation and prognosis in breast carcinoma. The quantitativeand qualitative measurement or p53 protein expression showed a Ⅰwerful evidence in evaluatingprognosis of bcl-2 were more significant in evaluating poor prognosis of breast carcinoma. A relationship between bcl-2 and ER, PR showed a better value for response to endocrine therapy in breastcarcinoma patients. 展开更多
关键词 breast carcinoma P53 protein bcl-2 protein PCNA image analysis technique
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Bcl-2蛋白质家族调控细胞凋亡机制的研究进展 被引量:61
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作者 尹智勇 杨俊元 祁宏 《信阳师范学院学报(自然科学版)》 CAS 北大核心 2017年第2期340-344,共5页
细胞凋亡是一种受基因调控的响应凋亡刺激的细胞程序性死亡方式.通过线粒体途径引发的凋亡主要由Bcl-2(B-cell lymphoma 2)蛋白质家族成员之间复杂的相互作用进行调控,然而科学界对其具体的相互作用模式一直存在争议.首先综述了近年来Bc... 细胞凋亡是一种受基因调控的响应凋亡刺激的细胞程序性死亡方式.通过线粒体途径引发的凋亡主要由Bcl-2(B-cell lymphoma 2)蛋白质家族成员之间复杂的相互作用进行调控,然而科学界对其具体的相互作用模式一直存在争议.首先综述了近年来Bcl-2蛋白质家族成员之间相互作用的生物学机制,然后总结了细胞凋亡具有双稳性和该家族成员相互作用模式的数学模型,最后通过对目前流行的3种作用模式(即直接激活模式、间接激活模式、统一模式)进行数值模拟和分岔分析,认为统一模式是更合理的作用模式.以期能更好地理解病理细胞中可能存在的作用机制,从而为因凋亡异常引起的癌症、阿尔兹海默症等疾病的治疗和控制提供思路. 展开更多
关键词 细胞凋亡 bcl-2蛋白质家族 统一模式 双稳性 癌症治疗
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Bcl-2家族对线粒体质量控制的调控研究 被引量:13
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作者 孙秀玉 刘立亚 +1 位作者 吴宥熹 黄秀兰 《中国药理学通报》 CAS CSCD 北大核心 2015年第12期1633-1636,共4页
线粒体质量控制是维持细胞生存及生存状态的重要机制,通过对线粒体形态、数量与质量的多维调控,维持细胞内稳态。研究发现Bcl-2家族与线粒体多种功能的调控密切相关,并参与调控线粒体自噬/细胞凋亡互调节及线粒体分裂、融合的动态变化,... 线粒体质量控制是维持细胞生存及生存状态的重要机制,通过对线粒体形态、数量与质量的多维调控,维持细胞内稳态。研究发现Bcl-2家族与线粒体多种功能的调控密切相关,并参与调控线粒体自噬/细胞凋亡互调节及线粒体分裂、融合的动态变化,是线粒体质量控制的关键调控因子。该文主要综述Bcl-2家族对线粒体质量控制的影响及其主要调控机制。 展开更多
关键词 bcl-2家族蛋白 线粒体质量控制 线粒体自噬 细胞凋亡 线粒体分裂与融合 BNIP3 PINK1-Parkin通路
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Bcl-2家族蛋白和乙肝病毒x蛋白在肝癌组织中的表达和意义 被引量:2
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作者 张晓东 东楠 +9 位作者 叶丽虹 殷丽辉 汪宁 张航 尤嘉琮 王洪辉 沈中阳 孙智才 魏国红 梅兴明 《南开大学学报(自然科学版)》 CAS CSCD 北大核心 2003年第4期84-88,共5页
应用免疫组织化学方法检测了34例肝癌组织及其相对应的癌旁组织,探讨了Bcl-2家族中七种基因(包括促凋亡基因Bak、Bad、Bid、Bax和Bcl-xs及抑凋亡基因Bcl-2、Bcl-w)和乙肝病毒三种抗原(包括HBsAg、HBcAg和HBxAg)在肝癌组织中的表达及意义... 应用免疫组织化学方法检测了34例肝癌组织及其相对应的癌旁组织,探讨了Bcl-2家族中七种基因(包括促凋亡基因Bak、Bad、Bid、Bax和Bcl-xs及抑凋亡基因Bcl-2、Bcl-w)和乙肝病毒三种抗原(包括HBsAg、HBcAg和HBxAg)在肝癌组织中的表达及意义,结果显示:在肝癌组织中HBsAg、HBcAg和HBxA的阳性率分别为58.8%、26.5%和76.5%、Bcl-2七种蛋白的阳性率分别为58.8%(Bak)、55.9%(Bad)、44.1%(Bid)、41.2%(Bax)、29.4%(Bcl-xs)、35.3%(Bcl-w)和41.2%(Bcl-2)。这七种Bcl-2蛋白的表达均位于肝癌细胞的胞浆,多呈弥漫性分布,少数阳性颗粒呈散在性分布,研究发现,Bcl-2家族中抑凋亡基因Bcl-w和Bcl-2在癌组织中表达的阳性率明显高于癌旁组织(P<O.05),本结果表明,Bcl-2家族蛋白在HBV感染的肝癌组织中过量表达,参与肝细胞的凋亡调控,与肝癌的发生和发展有关, 展开更多
关键词 肝细胞肝癌 乙肝病毒X蛋白 bcl-2家族 细胞凋亡 免疫组化
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Bcl-2家族蛋白小分子抑制剂的研究进展 被引量:3
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作者 张磊 王京 +1 位作者 李文赟 姚其正 《国外医药(抗生素分册)》 CAS 2014年第5期196-200,I0002,共6页
Bcl-2家族蛋白是细胞凋亡途径中一种重要的蛋白,在肿瘤的发生及转移中起着重要的作用。由于Bcl-2家族蛋白在多种癌细胞中高度表达,因此,对其干预成为一种新型肿瘤治疗策略,Bcl-2家族蛋白也成为抗肿瘤的热门靶点之一。本文总结了近年来Bc... Bcl-2家族蛋白是细胞凋亡途径中一种重要的蛋白,在肿瘤的发生及转移中起着重要的作用。由于Bcl-2家族蛋白在多种癌细胞中高度表达,因此,对其干预成为一种新型肿瘤治疗策略,Bcl-2家族蛋白也成为抗肿瘤的热门靶点之一。本文总结了近年来Bcl-2家族蛋白小分子抑制剂的研究进展。 展开更多
关键词 bcl-2家族蛋白 小分子抑制剂 抗肿瘤
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Bcl-2家族参与β-淀粉样蛋白对PC12细胞的致凋亡作用 被引量:2
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作者 邵梅 陈生弟 +1 位作者 刘振国 刘军 《中国神经科学杂志》 CSCD 2003年第3期161-166,共6页
目的 :研究bcl 2家族 (主要是bcl xl和bax)基因及相关蛋白是否参与水溶性淀粉样蛋白对培养的大鼠嗜铬细胞瘤细胞的毒性作用。方法 :应用电镜和DNA电泳判断细胞损伤途径 ,应用RT PCR ,免疫细胞化学和免疫印迹判断bcl 2家族及其相关蛋白... 目的 :研究bcl 2家族 (主要是bcl xl和bax)基因及相关蛋白是否参与水溶性淀粉样蛋白对培养的大鼠嗜铬细胞瘤细胞的毒性作用。方法 :应用电镜和DNA电泳判断细胞损伤途径 ,应用RT PCR ,免疫细胞化学和免疫印迹判断bcl 2家族及其相关蛋白是否参与淀粉样蛋白的损伤作用。结果 :10 μmol/LAβ2 5 35作用 2 4h后 ,电镜和DNA电泳均显示Aβ2 5 35可以导致PC12细胞凋亡 ;RT PCR表明药物作用后 6h ,bcl xlmRNA表达量减少而baxmRNA表达量增加 ;免疫印迹和免疫细胞化学结果显示药物作用后 2 4h ,Bax蛋白增加而Bcl xl无明显改变。结论 :水溶性淀粉样蛋白可以导致神经细胞凋亡 ,bcl 2家族参与了作用环节 ,对阿尔茨海默病的发病起着重要的作用。 展开更多
关键词 bcl-2家族 Β-淀粉样蛋白 PC12细胞 细胞凋亡 阿尔茨海默病
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Bcl-2家族蛋白在Ad.mda-7介导HepG2细胞凋亡中的变化 被引量:1
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作者 吉文伟 薛新波 +4 位作者 郑建伟 陈堃 于愿 王从俊 胡回忆 《临床外科杂志》 2008年第3期173-175,共3页
目的观察Bcl-2家族蛋白在Ad.mda-7介导HepG2细胞凋亡中的变化,初步探讨Ad.mda-7介导肝癌细胞的凋亡机制。方法将携带人MDA-7/IL-24基因的腺病毒转染HepG2和L02,通过四甲基偶氮哩蓝染色法(MTT)及Hoechst染色观察MDA-7/IL-24对肝癌细胞He... 目的观察Bcl-2家族蛋白在Ad.mda-7介导HepG2细胞凋亡中的变化,初步探讨Ad.mda-7介导肝癌细胞的凋亡机制。方法将携带人MDA-7/IL-24基因的腺病毒转染HepG2和L02,通过四甲基偶氮哩蓝染色法(MTT)及Hoechst染色观察MDA-7/IL-24对肝癌细胞HepG2和正常肝胚细胞L02的生长抑制和杀伤作用。Annexin V和PI双染后流式细胞仪检测细胞的凋亡。蛋白免疫印迹法(Western blot)检测Bcl-2家族蛋白的变化。结果Ad.mda-7能明显抑制肝癌细胞HepG2的生长,但对正常肝胚细胞L02没有明显抑制增殖作用。Hoechst染色和流式细胞仪提示Ad.mda-7能明显诱导肝癌细胞HepG2细胞的凋亡,但对正常肝胚细胞L02没有明显毒副作用。Western blot说明抑制凋亡的蛋白Bcl-2和Bcl-xl的表达在HepG2明显下降,在L02中则没有变化;而促凋亡蛋白Bax在HepG2和L02都升高。结论Ad.mda-7转染HepG2后,促凋亡(Bax)与抑凋亡蛋白(Bcl-2和Bcl-xl)的比率发生改变,进而发生凋亡。 展开更多
关键词 Ad.mda-7 HEPG2 凋亡 bcl-2家族蛋白
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缺氧诱导因子-1α和BCL-2/腺病毒E1B19 kDa相关蛋白3在中耳胆脂瘤表达及意义 被引量:1
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作者 岑瑞祥 赵凯 +4 位作者 万浪 彭聪 曹炜 刘原宙 龚国清 《中国耳鼻咽喉头颈外科》 CSCD 2019年第11期621-623,共3页
目的探讨缺氧诱导因子-1α(hypoxia inducible factor-1,HIF-1α)和BCL-2/腺病毒E1B19KDa相关蛋白3(Bcl2/adenovirus E1B 19 kD interacting protein 3,BNIP3)在中耳胆脂瘤中的表达及胆脂瘤上皮的凋亡情况。方法采用免疫组织化学方法检... 目的探讨缺氧诱导因子-1α(hypoxia inducible factor-1,HIF-1α)和BCL-2/腺病毒E1B19KDa相关蛋白3(Bcl2/adenovirus E1B 19 kD interacting protein 3,BNIP3)在中耳胆脂瘤中的表达及胆脂瘤上皮的凋亡情况。方法采用免疫组织化学方法检测30例中耳胆脂瘤标本与18例外耳道皮肤标本中HIF-1α和BNIP3蛋白的表达情况,使用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling,Tunel)检测20例中耳胆脂瘤标本和18例外耳道皮肤标本的凋亡情况。使用Pearson相关分析检验HIF-1α和BNIP3蛋白之间的相关性。结果 HIF-1α在胆脂瘤组和对照组的平均光密度分别为0.16±0.07和0.08±0.03,两组比较差异有统计学意义(t=4.279,P<0.01);BNIP3在胆脂瘤组和对照组的平均光密度分别为0.16±0.08和0.11±0.06,两组比较差异有统计学意义(t=2.463,P=0.0185);经pearson相关分析,在胆脂瘤上皮中,HIF-1α和BNIP3之间呈正相关(r=0.418,P=0.003);Tunel染色中,凋亡指数在胆脂瘤组和对照组分别为(52.8±12.5)%和(9.99±2.97)%,两组比较差异有统计学意义(t=14.166,P<0.01)。结论 HIF-1α和BNIP3在中耳胆脂瘤中的异常表达可能与胆脂瘤的高凋亡特性有关。 展开更多
关键词 胆脂瘤 中耳(Cholesteatoma Middle Ear) 对比研究(Comparative Study) 细胞凋亡(Apoptosis) 缺氧诱导因子-1α(hypoxia-inducible factor-1α) bcl-2/腺病毒E1B19 kDa相关蛋白3(Bcl2/adenovirus E1B 19 kD interacting protein 3)
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