检索结果-内蒙古大学图书馆

作者：陶军南华大学

学位级别：硕士

子痫前期（preeclampsia,PE）作为一种妊娠期高血压疾病,其表现主要为妊娠20周后收缩压（≥140mm Hg）和（或）舒张压（≥90mm Hg）升高,伴或不伴蛋白尿及各系统功能紊乱,目前只能通过终止妊娠治疗,而其病因及机制尚未明确。目前研究认... 详细信息

子痫前期（preeclampsia,PE）作为一种妊娠期高血压疾病,其表现主要为妊娠20周后收缩压（≥140mm Hg）和（或）舒张压（≥90mm Hg）升高,伴或不伴蛋白尿及各系统功能紊乱,目前只能通过终止妊娠治疗,而其病因及机制尚未明确。目前研究认为其发生可能涉及滋养层细胞异常死亡,炎性因子分泌和氧化应激。妊娠期糖尿病（gestational diabetes mellitus,GDM）和糖尿病合并妊娠都伴随着孕妇血糖的升高,而高血糖与PE发生密切相关,被认为是PE的独立危险因素,然而其机制尚未明确。胎盘生长因子（placenta growth factor,PLGF）是一种分泌蛋白,能够促进内皮细胞增殖和血管新生,调控滋养层细胞增殖及炎症反应。因此,其正常水平对胎盘和胎儿发育意义重大,然而PE病人中常出现PLGF的下降。因此,探索高血糖和PE之间的关系及PLGF在其中的作用十分重要。前期研究表明,在高糖（high glucose,HG）处理后,外源补充PLGF可恢复滋养层细胞的增殖和迁移能力;动物实验表明,注射PLGF可缓解模型鼠的PE症状,提示PLGF有潜在治疗子痫前期的作用。而研究PLGF在高糖影响下的作用对PE的治疗有重要的意义。炎症介质释放和损伤细胞清除障碍是高血糖引起PE的重要方式。及时清除损伤细胞,抑制炎症因子的释放以缓解高血糖带来的损伤,是治疗PE的重要策略。焦亡是一种促炎细胞死亡,同时也是PE的重要病理特征,而自噬抑制导致促炎介质的增加是引发焦亡的因素之一,高血糖伴随的PE可检测到焦亡细胞和自噬水平的下降。因此,本研究的目的是探讨PLGF是否可以通过调节自噬进而影响HG引起的滋养层细胞焦亡,并探讨其潜在机制。第一部分:高糖对滋养层细胞焦亡及PLGF表达的影响【目的】观察高糖对滋养层细胞焦亡和PLGF表达的影响。【方法】首先,明确高血糖对胎盘的影响。根据美国糖尿病学会《孕期糖尿病诊治指南》将20名孕妇分为2组:（1）对照组:为健康孕妇;（2）GDM组:诊断为孕期糖尿病孕妇。记录孕妇病史相关信息。孕妇分娩后,取胎盘脐带根部清洗后迅速放于干冰上保存。H&E染色观察胎盘病理改变,Western blot和免疫荧光检测焦亡相关分子表达水平。体外培养胎盘滋养层细胞HTR8-S/Vneo,观察高糖对滋养层细胞增殖迁移能力影响。用甘露醇（25m M）设置高渗对照,不同浓度的D-葡萄糖（5,15,25m M）处理HTR8-S/Vneo细胞（24h）,随后使用CCK8、细胞划痕、transwell分别检测细胞增殖、迁移、侵袭能力。检测高糖对滋养层细胞衰老和损伤的影响。采用不同浓度的D-葡萄糖（5,15,25m M）处理HTR8-S/Vneo细胞（24h）,衰老相关β-半乳糖苷酶（senescence associatedβ-galactosidase,SA-β-Gal）染色,SOD和MDA检测滋养层细胞衰老和氧化损伤水平。为明确高糖是否引起滋养层细胞焦亡的发生,体外培养HTR8-S/Vneo细胞,用甘露醇（25m M）设置高渗对照,采用25m M的D-葡萄糖处理HTR8-S/Vneo细胞24h,采用Western blot,qRT-PCR和ELISA检测焦亡相关分子,检测乳酸脱氢酶（lactate dehydrogenase,LDH）和PI/Hoechst33342双染阳性细胞衡量细胞死亡水平。为探究高糖对滋养层细胞PLGF的表达水平。用甘露醇（25m M）设置高渗对照,不同浓度的D-葡萄糖（5,15,25,30m M）处理HTR8-S/Vneo细胞（24h）,通过western blot和qRT-PCR检测PLGF在蛋白质和mRNA水平的表达,及高糖处理后胞内PLGF的定位是否发生变化。高糖处理细胞24h后,通过免疫荧光检测PLGF的分布,western blot检测胞质和胞浆表达水平。【结果】与对照组比较,GDM组血管管腔数量减少,焦亡相关蛋白NLRP3,caspase1和IL-1β表达水平增加,表明高血糖可抑制胎盘生长发育,同时促进炎性介质的表达。体外实验表明,当D-葡萄糖浓度达到25m M时,细胞活性受到抑制（P<0.01）,且随时间延长损伤未见恢复（24h:P<0.05;48h:P<0.05）。细胞划痕实验表明,在D-葡萄糖浓度为25m M的条件下,细胞迁移能力下降,且48h内损伤未见恢复（24h:P<0.001;48h:P<0.001）。Transwell实验表明,相对于高渗对照组,25m M的D-葡萄糖处理24h后,细胞侵袭能力下降（P<0.001）。SA-b-Gal染色结果表明,相对于高渗对照组25m M的D-葡萄糖处理组阳性面积升高,表明细胞衰老水平增加,同时SOD水平下降,MDA含量增加。因此,25m M

关键词：妊娠期糖尿病子痫前期胎盘生长因子焦亡线粒体自噬 bnip3 PINK1 Parkin

来源：评论

学校读者我要写书评

暂无评论

Bmal1在糖尿病心肌缺血再灌注损伤易感性中的作用

Bmal1在糖尿病心肌缺血再灌注损伤易感性中的作用

引用

作者：邓捷山西医科大学

学位级别：硕士

目的:探索Bmal1-Sirt3途径在糖尿病MI/RI易感性中的作用及其与线粒体自噬之间的关系。方法:健康雄性清洁级SD大鼠,体重200～220g。采用高脂高糖饲料喂养+腹腔注射链脲佐菌素方法制备2型糖尿病模型。取造模成功的大鼠30只,采用随机数字表... 详细信息

目的:探索Bmal1-Sirt3途径在糖尿病MI/RI易感性中的作用及其与线粒体自噬之间的关系。方法:健康雄性清洁级SD大鼠,体重200～220g。采用高脂高糖饲料喂养+腹腔注射链脲佐菌素方法制备2型糖尿病模型。取造模成功的大鼠30只,采用随机数字表法,将其分为3组(n=10):糖尿病假手术组(DM-S组)、糖尿病缺血再灌注组(DM-I/R组)、糖尿病+SR8278缺血再灌注组(DMS-I/R组)。另取健康大鼠30只,采用随机数字表法,将其分为3组(n=10):正常假手术组(N-S组)、正常缺血再灌注组(N-I/R组)、正常+SR8278缺血再灌注组(NS-I/R组)。采用阻断左冠状动脉前降支45min,再灌注24h的方法制备心肌缺血再灌注损伤模型。DMS-I/R组和NS-I/R组于手术前7天每天T8时腹腔注射SR8278(Rev-erbα拮抗剂)50mg/kg。所有大鼠严格进行12h光/暗循环模式,均在T8时进行手术操作。心肌再灌注24h后,行HE染色,光镜下观察病理学结果;采用TTC染色法检测心肌梗死体积;Western blot法检测心肌组织Bmal1、Sirt3和bnip3表达。结果:N-S组和DM-S组无心肌梗死。与N-S组比较,N-I/R组、NS-I/R组、DM-I/R组、DMS-I/R组心肌梗死体积增大(P<0.05);与N-I/R组比较NS-I/R组心肌梗死体积减小(P<0.05);与DM-S组比较,DM-I/R组、DMS-I/R组心肌梗死体积增大(P<0.05);与DM-I/R组比较,DMS-I/R组心肌梗死体积减小(P<0.05)。与N-S组比较,N-I/R组、DM-S组、DM-I/R组、Bmal1、Sirt3蛋白表达下调,Nlrp3、bnip3蛋白表达上调(P<0.05);与N-I/R组比较,NS-I/R组Bmal1、Sirt3、bnip3蛋白表达上调,Nlrp3蛋白表达下调(P<0.05);与N-I/R组比较,DM-I/R组Bmal1、Sirt3蛋白表达下调,Nlrp3、bnip3蛋白表达上调(P<0.05);与DM-S组比较,DM-I/R组、DMS-I/R组Bmal1、Sirt3蛋白表达下调,Nlrp3、bnip3蛋白表达上调(P<0.05);与DM-I/R组比较,DMS-I/R组Bmal1、Sirt3、bnip3蛋白表达上调,Nlrp3蛋白表达下调(P<0.05);与NS-I/R组比较,DMS-I/R组Bmal1、Sirt3蛋白表达下调,Nlrp3、bnip3蛋白表达上调(P<0.05)。结论:1.缺血再灌注损伤可以诱导非糖尿病大鼠心肌Bmal1表达下调,糖尿病因素使大鼠心肌细胞Bmal1表达进一步下调。***1通过激活Sirt3途径诱导线粒体bnip3自噬途径和抑制Nlrp3炎性小体,在糖尿病心肌缺血再灌注中发挥心肌保护作用。

关键词：糖尿病 Bmal1 Sirt3 bnip3 心肌再灌注损伤线粒体自噬

来源：评论

学校读者我要写书评

暂无评论

Hif-2α通过线粒体自噬调节酒精性脂肪肝脂质代谢

Hif-2α通过线粒体自噬调节酒精性脂肪肝脂质代谢

引用

作者：吴美飞安徽医科大学

学位级别：硕士

酒精滥用与酒精性肝病(Alcoholic liver disease,ALD)是美国和世界范围内的一个主要公共卫生问题。作为ALD的最初阶段,酒精性脂肪性肝病(Alcoholic fatty liver disease,AFLD)的主要特点是脂质在肝细胞中不断积累并可能进一步发展为酒... 详细信息

酒精滥用与酒精性肝病(Alcoholic liver disease,ALD)是美国和世界范围内的一个主要公共卫生问题。作为ALD的最初阶段,酒精性脂肪性肝病(Alcoholic fatty liver disease,AFLD)的主要特点是脂质在肝细胞中不断积累并可能进一步发展为酒精性脂肪性肝炎(Alcoholic steatohepatitis,ASH)、酒精性肝硬化(Alcoholic cirrhosis,AC)和肝细胞癌(Hepatocellular carcinoma,HCC)等不可逆肝损害。因此,寻找有效的脂质积累靶点和处理方法,在初始阶段阻断ALD的进一步发展对于ALD的治疗是必不可少的。脂肪酸β-氧化参与肝脏脂质代谢,而脂质代谢紊乱与AFLD密切相关。研究表明,低氧诱导因子-2a(Hypoxia-inducible factor-2a,Hif-2α)在肝病患者中表达水平很高,Hif-2α失活可通过脂肪酸代谢调控作用逆转肝癌的进展[1]。而在AFLD中,Hif-2α与脂肪酸β-氧化之间的具体调控机制尚未研究。本实验旨在探讨Hif-2α在AFLD中的作用以及Hif-2α调控肝脏脂肪变性可能的分子机制。研究内容如下:***-2α在乙醇喂养的小鼠肝脏和乙醇诱导的AML-12细胞中的表达。我们采用经典的Gao-Binge造模法,在小鼠体内制造AFLD模型。油红O染色结果显示,乙醇喂养组小鼠肝脏呈现明显脂质积累,且血清ALT、AST活性、TG、T-CHO含量和肝指数也明显上升;H&E染色结果显示,乙醇喂养组小鼠肝脏呈现一定程度肝损伤;体外油红O染色结果同样表明,100 m M乙醇刺激AML-12细胞48h后出现大量脂质沉积。在乙醇喂养的小鼠肝脏和乙醇诱导的AML-12细胞中,参与脂肪酸β-氧化的两个关键酶:CPT-1α和MCAD表达水平均下降。IHC染色、RT-q PCR和Western blotting结果一致显示:Hif-2α在乙醇喂养的小鼠肝脏和乙醇诱导的AML-12细胞中呈现高表达。IF染色结果显示,乙醇刺激AML-12细胞48h后,Hif-2α荧光强度明显增加,且Hif-2α主要在细胞核内染色水平提高,Western blotting分析进一步证实了这一发现。***-2α对乙醇喂养的小鼠肝脏和乙醇诱导的AML-12细胞中脂肪酸β-氧化水平的影响。为了进一步确定Hif-2α与脂肪酸β-氧化之间的潜在关系,自乙醇喂养小鼠第10天起,每日灌胃给予Hif-2α特异性抑制剂PT2399(10mg/kg)一次,持续一周。油红O染色和H&E染色分别显示,PT2399治疗组小鼠肝脏脂滴数量减少、肝损伤程度减轻;小鼠血清ALT、AST活性、T-CHO、TG含量和肝指数均显著下降;脂肪酸β-氧化相关蛋白:MCAD、CPT-1α表达水平上升。在AML-12细胞中,采用Hif-2α-siRNA质粒建立Hif-2α沉默细胞模型,同时给予乙醇刺激AML-12细胞48h。Western blotting结果显示,Hif-2α-siRNA处理组中MCAD和CPT-1α蛋白表达水平上升。细胞上清液TG生化分析显示,Hif-2α-siRNA处理组中脂质沉积明显减少。采用2.0 uM的PT2399处理AML-12细胞并给予乙醇刺激48 h后,脂肪酸β-氧化相关蛋白:CPT-1α与MCAD表达变化与Hif-2α-siRNA处理组中相一致。油红O染色和TG生化分析结果也与Hif-2α-siRNA处理组中相一致。***-2α对乙醇喂养的小鼠肝脏和乙醇诱导的AML-12细胞中bnip3依赖的线粒体自噬活性的影响。RT-qPCR和Western blotting结果显示,乙醇喂养组线粒体自噬相关基因:bnip3、Beclin1和LC3II的m RNA和蛋白表达水平下降,而这一现象被PT2399所逆转。透射电镜(TEM)分析显示,对照组小鼠肝脏中线粒体形态正常并分裂活跃,而乙醇喂养组小鼠肝脏线粒体大量肿胀而无分裂,且脂肪空泡数量增加,自噬体数量减少。经PT2399治疗后,大部分损伤线粒体恢复到几乎完整的线粒体形态和分裂活性,且脂肪空泡数量减少,自噬体数量增加。Western blotting进一步分析显示,体外乙醇组中bnip3、Beclin1和LC3II/LC3I蛋白表达水平下降。IF分析表明,乙醇组中LC3与Mito Tracker Red(MTR)共定位水平下降、bnip3和LC3荧光斑点重叠数量减少。将Hif-2α-siRNA转染至AML-12细胞中,同时给予乙醇刺激48 h。Western blotting结果显示,Hif-2α-siRNA处理组中bnip3、Beclin1和LC3II/LC3I蛋白表达水平有所提高,这与PT2399处理组中

关键词： Hif-2α bnip3 线粒体自噬脂肪酸β-氧化酒精性脂肪肝

来源：评论

学校读者我要写书评

暂无评论

X染色体连锁的凋亡抑制蛋白及bnip3在脑缺血再灌注损伤中作用的研究进展

引用

广东医学 2015年第22期36卷 3555-3558页

作者：邱振方李世英华北理工大学附属医院神经内一科河北唐山063000 华北理工大学

脑缺血再灌注损伤（CIRI）,是指脑缺血导致组织坏死后血管再通,而缺血性损伤却进一步加重的现象,是脑血管疾病损伤的重要病理生理基础。CIRI的病理过程涉及细胞凋亡、自由基损伤、炎症反应、Ca-（2＋）超载、血-脑脊液屏障受损及兴奋性... 详细信息

脑缺血再灌注损伤（CIRI）,是指脑缺血导致组织坏死后血管再通,而缺血性损伤却进一步加重的现象,是脑血管疾病损伤的重要病理生理基础。CIRI的病理过程涉及细胞凋亡、自由基损伤、炎症反应、Ca-（2＋）超载、血-脑脊液屏障受损及兴奋性神经递质的释放等。

关键词：缺血再灌注损伤 bnip3 X染色体连锁凋亡蛋白细胞凋亡血-脑脊液屏障缺血性脑损伤自由基损伤缺血性损伤 Caspase

来源：评论

学校读者我要写书评

暂无评论

Upregulation of bnip3 mediated by ERK/HIF-1α pathway induces autophagy and contributes to anoikis resistance of hepatocellular carcinoma cells

引用

FUTURE ONCOLOGY 2014年第8期10卷 1387-1398页

作者： Sun, Lei Li, Tao Wei, Qing Zhang, Ying Jia, Xiaoqing Wan, Zhengkun Han, Lihui Shandong Univ Sch Med Dept Immunol Jinan 250012 Peoples R China Shandong Univ Prov Hosp Dept Infect Dis Jinan 250021 Peoples R China Shandong Univ Qilu Hosp Dept Gastroenterol Jinan 250012 Peoples R China

Aim: Acquisition of anoikis resistance is the hallmark of cancer and has been shown to be involved in metastasis of melignant cells. Our previous work showed that anoikis resistance is associated with the metastasis of hepatocellular carcinoma (HCC) cells. The aim of this study is to elucidate the mechanisms of this course. Materials & methods: Expression of bnip3 and HIF-1 alpha at the mRNA and protein level in HCC cells were detected by realtime PCR and western blot, respectively. Autophagy activation and signaling transduction pathway were detected by western blot. Cell viabilities were detected by CCK8 assay and trypan blue exclusion assay. Results: Upregulation of bnip3 promoted the activation of autophagy, one type of cell survival strategy in response to external stress, by suppressing mTOR/S6K1 signaling system. The upregulation of bnip3 was mediated by ERK/HIF-1 alpha pathway, which further contributed to anoikis resistance of HCC cells through the mTORC1 signaling pathway. Conclusion: Upregulation of bnip3 contributs to anoikis resistance of HCC cells, and bnip3 may serve as a novel therapeutic target for manipulation of cancer metastasis.

关键词： anoikis resistance autophagy bnip3 hepatocellular carcinoma mTOR/S6K1

来源：评论

学校读者我要写书评

暂无评论

bnip3 Suppresses PINK1 Proteolytic Cleavage to Promote Mitophagy

BNIP3 Suppresses PINK1 Proteolytic Cleavage to Promote Mitop...

引用

第十四次全国医学遗传学学术会议

作者： Zhang TM Xue L Li L Tang CY Wan ZQ Wang RX Zeng ZT Tan JQ Tang BS W.Andy Tao Zhang ZH The State Key Laboratory of Medical Genetics Xiangya Medical SchoolCentral South University Department of Biochemistry Purdue University Department of Neurology Xiangya HospitalCentral South University Collaborative Innovation Center for Brain Science Fudan University

Objective:Mutations in PINK1 gene cause recessive form of Parkinson's disease(PD).The PINK1 gene encodes a mitochondrial protein kinase that is processed by mitochondrial proteases resulting in two smaller proteolytic *** not only protects cells against mitochondrial dysfunction and apoptosis,but also regulates clearance of damaged mitochondria together with ***2/adenovirus E1B 19kDa interacting protein 3(bnip3)is a mitochondrial BH3-only protein known to induce *** present study is to explore whether PINK1/Parkin and bnip3 function in the same pathway to regulate mitochondria ***:The interaction between PINK1 and bnip3was determined by co-immunoprecipition *** induction was analyzed with parkin and GFP-LC3 ***:Our results reveal that bnip3 interacts with PINK1 to promote stabilization and accumulation of full-length PINK1 on outer membrane of damaged mitochondria,therefore,to facilitate parkin recruitment to ***:The results suggest that bnip3 plays an essential role in PINK1/parkinmediated mitophagy and likely contributes to PD pathogenesis.

关键词： Parkinson's disease PINK1 bnip3 mitophagy

来源：评论

学校读者我要写书评

暂无评论

bnip3 Interacting with LC3 Triggers Excessive Mitophagy in Delayed Neuronal Death in Stroke

引用

CNS NEUROSCIENCE & THERAPEUTICS 2014年第12期20卷 1045-1055页

作者： Shi, Ruo-Yang Zhu, Sheng-Hua Li, Victor Gibson, Spencer B. Xu, Xing-Shun Kong, Ji-Ming Univ Manitoba Fac Med Dept Human Anat & Cell Sci Winnipeg MB R3E 0J9 Canada Univ Manitoba Fac Med Dept Pharmacol & Therapeut Winnipeg MB R3E 0J9 Canada Univ Manitoba Manitoba Inst Cell Biol Winnipeg MB R3E 0J9 Canada Univ Manitoba Fac Med Dept Biochem & Med Genet Winnipeg MB R3E 0J9 Canada Soochow Univ Inst Neurosci Suzhou Jiangsu Peoples R China

IntroductionA basal level of mitophagy is essential in mitochondrial quality control in physiological conditions, while excessive mitophagy contributes to cell death in a number of diseases including ischemic stroke. Signals regulating this process remain unknown. bnip3, a pro-apoptotic BH3-only protein, has been implicated as a regulator of mitophagy. AimsBoth in vivo and in vitro models of stroke, as well as bnip3 wild-type and knock out mice were used in this study. ResultsWe show that bnip3 and its homologue bnip3L (NIX) are highly expressed in a delayed manner and contribute to delayed neuronal loss following stroke. Deficiency in bnip3 significantly decreases both neuronal mitophagy and apoptosis but increases nonselective autophagy following ischemic/hypoxic insults. The mitochondria-localized bnip3 interacts with the autophagosome-localized LC3, suggesting that bnip3, similar to NIX, functions as a LC3-binding receptor on mitochondria. Although NIX expression is upregulated when bnip3 is silenced, up-regulation of NIX cannot functionally compensate for the loss of bnip3 in activating excessive mitophagy. ConclusionsNIX primarily regulates basal level of mitophagy in physiological conditions, whereas bnip3 exclusively activates excessive mitophagy leading to cell death.

关键词： bnip3 LC3 Mitophagy Neonatal stroke NIX

来源：评论

学校读者我要写书评

暂无评论

Structure, function, and epigenetic regulation of bnip3: a pathophysiological relevance

引用

MOLECULAR BIOLOGY REPORTS 2014年第11期41卷 7705-7714页

作者： Vasagiri, Nagarjuna Kutala, Vijay Kumar Nizams Inst Med Sci Dept Clin Pharmacol & Therapeut Hyderabad Andhra Pradesh India Ctr Cellular & Mol Biol Annexure II Hyderabad Andhra Pradesh India

BCL-2 [B-cell leukemia/lymphoma 2]/adeno-virus E1B 19KD interacting protein 3 (bnip3) is an atypical BH3 domain only containing member of Bcl2 family of proteins. bnip3 is known to be involved in various cellular processes depending on the cell type and conditions and also shown to play a role in various disease conditions including myocardial ischemia, autophagy and apoptosis. Though its role in autophagy and its pro-death activity have been reported in various studies, recent findings have shown its contradictory role in the regulation of these cellular processes. The various studies have shown its epigenetic regulation in disease development and progression and also found to be cytoprotective. In this review, we have focused on the structural and functional aspects of bnip3 in relation to recent advances of its role in autophagy and apoptosis. Also its role of epigenetic regulation of several genes involved in various diseases was also discussed.

关键词： bnip3 Apoptosis Autophagy Epigenetic regulations Mitochondrial permeabilization

来源：评论

学校读者我要写书评

暂无评论

bnip3 is involved in the regulation of cell fate under different hypoxia conditions through the induction of mitophagy or apoptosis

BNIP3 is involved in the regulation of cell fate under diffe...

引用

The 7th International Symposium on Autophagy

作者： ling He Li-Ying Wu Yao Di Wei-Jian Zong Xin Huang Tong Zhao Kui-Wu Wu Ming Fan Ling-Ling Zhu Beijing Institute of Basic Medical SciencesYun Beijing Institute of Basic Medical Sciences

bnip3 is regulated by hypoxia through hypoxia-inducible factor 1(HIF-1), which binds to hypoxia response element(HRE) in the promoter of bnip3 and activates its transcription. It is unknown how different degrees of hypoxia regulate bnip3 and what role bnip3 plays in determining cell fate with respect to regulation of mitophagy and apoptosis. In this study, we found that mitophagy was the dominant activity under moderate hypoxia(10% O2) and that apoptosis was the dominant activity under severe hypoxia(0.3% O2). The different activities were related to the differential regulation of bnip3 by varying degrees of hypoxia. Moderate hypoxia increased the bnip3 protein level, which promoted mitophagy and cell survival. Severe hypoxia decreased the bnip3 protein level, which resulted in apoptosis and cell death. Thus, we propose that the bnip3 protein level plays a pivotal role in determining the choice of mitophagy or apoptosis pathways. Unlike previous reports, we are the first to discover that bnip3 down-regulation rather than up-regulation leads to apoptosis and cell death.

关键词： bnip3 Mitophagy apoptosis hypoxia

来源：评论

学校读者我要写书评

暂无评论

bnip3 Upregulation by ERK and JNK Mediates Cadmium-Induced Necrosis in Neuronal Cells

引用

TOXICOLOGICAL SCIENCES 2014年第2期140卷 393-402页

作者： Wang, Bin Xiao, Jia-Li Ling, Yi-Hui Meng, Xiao-Jing Wu, Bing Yang, Xin-Yi Zou, Fei Southern Med Univ Sch Publ Hlth & Trop Med Dept Occupat Heath & Occupat Med Guangzhou 510515 Guangdong Peoples R China

Cadmium (Cd) is a toxic heavy metal that may cause neurological disorders. We studied the mechanism underlying Cd-mediated cell death in neuronal cells. In Cd-induced neurotoxicity, caspase-3 was only modestly activated, and accordingly, zVAD-fmk, a pan-caspase inhibitor, partially attenuated cell death. However, pretreatment with Necrox-2 or Necrox-5, two novel necrosis inhibitors, suppressed cell death more markedly compared with pretreatment with zVAD-fmk. Moreover, the necrosis inhibitors did not prevent cleavage of caspase-3. These results indicate that caspase-independent necrosis is more prevalent in Cd-induced neurotoxicity. Bcl-2 and adenovirus E1B-19 kDa-interacting protein 3 (bnip3) has been reported to be related to caspase-independent cell death. Cd treatment caused a dramatic upregulation of bnip3 mRNA and protein levels in vitro and in vivo. Furthermore, knockdown of bnip3 greatly inhibited Cd-induced cell death. Importantly, bnip3 RNAi decreased lactate dehydrogenase release and the percentage of propidium iodide-positive cells, two markers of necrotic cell death due to rupture of the cell membrane, whereas it had no effect on activation of caspase-3 in Cd-treated cells. These data suggest that bnip3 mediates caspase-independent necrosis, but not apoptosis. Moreover, our results indicate that induction of bnip3 by Cd may not be related to HIF-1 which is generally regarded as a mediator responsible for bnip3 expression. Finally, we show that mitogen-activated protein kinases (MAPKs) are activated by Cd in vitro and in vivo;ERK and JNK promote bnip3 upregulation and subsequent necrosis. Taken together, our results suggest bnip3, upregulated by activation of ERKand JNK, mediates Cd-induced necrosis in neuronal cells.

关键词： cadmium bnip3 MAPK cell death

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：