检索结果-内蒙古大学图书馆

Yap promotes hepatocellular carcinoma metastasis and mobilization via governing cofilin/F-actin/lamellipodium axis by regulation of JNK/bnip3/SERCA/CaMKII pathways

引用

REDOX BIOLOGY 2018年 14卷 59-71页

作者： Shi, Chen Cai, Yong Li, Yongheng Li, Ye Hu, Nan Ma, Sai Hu, Shunying Zhu, Pingjun Wang, Weihu Zhou, Hao Peking Univ Canc Hosp & Inst Dept Radiat Oncol Minist Educ Beijing Key Lab Carcinogenesis & Translat Res Beijing Peoples R China Peoples Liberat Army Gen Hosp Canc Ctr Dept Oncol Beijing Peoples R China Univ Wyoming Coll Hlth Sci Ctr Cardiovasc Res & Alternat Med Laramie WY 82071 USA Chinese Peoples Liberat Army Gen Hosp Dept Cardiol Beijing Peoples R China

Despite the increasingly important role of Hippo-Yap in hepatocellular carcinoma (HCC) development and progression, little insight is available at the time regarding the specifics interaction of Yap and cancer cells migration. Here, we identified the mechanism by which tumor-intrinsic Yap deletion resulted in HCC migratory inhibition. Yap was greatly upregulated in HCC and its expression promoted the cells migration. Functional studies found that knockdown of Yap induced JNK phosphorylation which closely bound to the bnip3 promoter and contributed to bnip3 expression. Higher bnip3 employed excessive mitophagy leading to mitochondrial dysfunction and ATP shortage. The insufficient ATP inactivated SERCA and consequently triggered intracellular calcium overload. As the consequence of calcium oscillation, Ca/calmodulin-dependent protein kinases II (CaMKII) was signaled and subsequently inhibited cofilin activity via phosphorylated modification. The phosphorylated cofilin failed to manipulate F-actin polymerization and lamellipodium formation, resulting into the impairment of lamellipodium-based migration. Collectively, our results identified Hippo-Yap as the tumor promoter in hepatocellular carcinoma that mediated via activation of cofilin/F-actin/lamellipodium axis by limiting JNK-bnip3-SERCA-CaMKII pathways, with potential application to HCC therapy involving cancer metastasis.

关键词： Yap JNK bnip3 SERCA CaMKII F-actin Cofilin Lamellipodium Migration

来源：评论

学校读者我要写书评

暂无评论

Upregulation of bnip3 and translocation to mitochondria mediates cyanide-induced apoptosis in cortical cells

引用

NEUROSCIENCE 2007年第1期150卷 159-167页

作者： Prabhakaran, K. Li, L. Zhang, L. Borowitz, J. L. Isom, G. E. Purdue Univ Dept Med Chem & Mol Pharmacol W Lafayette IN 47907 USA

Bcl-2/adenovirus E1B 19-kDa-interacting protein 3 (bnip3), a BcI-2 homology domain 3 (BH3) domain only protein, has been identified as a mitochondrial mediator of hypoxia-induced cell death. Since cyanide produces histotoxic anoxia (chemical hypoxia), the present study was undertaken in primary rat cortical cells to determine involvement of the bnip3 signaling pathway in cyanide-induced death. Over a 20 h exposure KCN increased bnip3 expression, followed by a concentration-related apoptotic death. To determine if bnip3 plays a role in the cell death, expression was either increased with bnip3 cDNA (bnip3(+)) or knocked down with small interfering RNA (RNAi). In bnip3(+) cells, cyanide-induced apoptotic death was markedly enhanced and preceded by reduction of mitochondrial membrane potential (Delta psi(m).), release of cytochrome c from mitochondria and elevated caspase 3 and 7 activity. Pretreatment with the pan-caspase inhibitor N-benzyioxycarbonyl-Ala-Asp-fluoromethyl ketone (zVAD-fmk) suppressed bnip3(+)-mediated cell death, thus confirming a caspase-dependent apoptosis. On the other hand, bnip3 knockdown by RNAi or antagonism of bnip3 by a transmembrane-deleted dominant-negative mutant (bnip3 Delta TM) markedly reduced cell death. Immunohistochemical imaging showed that cyanide stimulated translocation of bnip3 from cytosol to mitochondria and displacement studies with bnip3 Delta TM showed that integration of bnip3 into the mitochondrial outer membrane was necessary for the cell death. In bnip3+ cells, cyclosporin-A, an inhibitor of mitochondrial pore transition, blocked the cyanide-induced reduction of Delta psi(m) and decreased the apoptotic death. These results demonstrate in cortical cells that cyanide induces a rapid upregulation of bnip3 expression, followed by translocation to the mitochondrial outer membrane to reduce At m. This was followed by mitochondrial release of cytochrome c to execute a caspase-dependent cell death. (c) 2007 IBRO. Published by E

关键词： cyanide bnip3 apoptosis neurotoxicity

来源：评论

学校读者我要写书评

暂无评论

Hypoxia induces autophagic cell death in apoptosis-competent cells through a mechanism involving bnip3

引用

AUTOPHAGY 2008年第2期4卷 195-204页

作者： Azad, Meghan B. Chen, Yongqiang Henson, Elizabeth S. Cizeau, Jeannick McMillan-Ward, Eileen Israels, Sara J. Gibson, Spencer B. Univ Manitoba Manitoba Inst Cell Biol Winnipeg MB R3E 0V9 Canada Univ Manitoba Dept Biochem & Med Genet Winnipeg MB R3E 0V9 Canada Univ Manitoba CancerCare Manitoba Winnipeg MB R3E 0V9 Canada

Hypoxia (lack of oxygen) is a physiological stress often associated with solid tumors. Hypoxia correlates with poor prognosis since hypoxic regions within tumors are considered apoptosis-resistant. Autophagy (cellular "self digestion") has been associated with hypoxia during cardiac ischemia and metabolic stress as a survival mechanism. However, although autophagy is best characterized as a survival response, it can also function as a mechanism of programmed cell death. Our results show that autophagic cell death is induced by hypoxia in cancer cells with intact apoptotic machinery. We have analyzed two glioma cell lines (U87, U373), two breast cancer cell lines (MDA-MB-231, ZR75) and one embryonic cell line (HEK293) for cell death response in hypoxia (<1% O-2). Under normoxic conditions, all five cell lines undergo etoposide-induced apoptosis whereas hypoxia fails to induce these apoptotic responses. All five cell lines induce an autophagic response and undergo cell death in hypoxia. Hypoxia-induced cell death was reduced upon treatment with the autophagy inhibitor 3-methyladenine, but not with the caspase inhibitor z-VAD-fmk. By knocking down the autophagy proteins Beclin-1 or ATG5, hypoxia-induced cell death was also reduced. The pro-cell death Bcl-2 family member bnip3 (Bcl-2/adenovirus E1B 19kDa-interacting protein 3) is upregulated during hypoxia and is known to induce autophagy and cell death. We found that bnip3 over-expression induced autophagy, while expression of bnip3 siRNA or a dominant-negative form of bnip3 reduced hypoxia-induced autophagy. Taken together, these results suggest that prolonged hypoxia induces autophagic cell death in apoptosis-competent cells, through a mechanism involving bnip3.

关键词： autophagy hypoxia autophagic cell death bnip3 cancer

来源：评论

学校读者我要写书评

暂无评论

Aconitine induces cardiomyocyte damage by mitigating bnip3-dependent mitophagy and the TNFα-NLRP3 signalling axis

引用

CELL PROLIFERATION 2020年第1期53卷 e12701-e12701页

作者： Peng, Fu Zhang, Nan Wang, Chunting Wang, Xiaoyun Huang, Wei Peng, Cheng He, Gu Han, Bo Sichuan Univ West China Hosp West China Sch Pharm State Key Lab Biotherapy Chengdu Sichuan Peoples R China Chengdu Univ Tradit Chinese Med Sch Pharm Key Lab Southwestern Chinese Med Resources Chengdu 611137 Sichuan Peoples R China

Objectives Aconitine, the natural product extracted from Aconitum species, is widely used for the treatment of various diseases, including rheumatism, arthritis, bruises, fractures and pains. However, many studies have reported cardiotoxicity and neurotoxicity caused by aconitine, but the detailed mechanism underlying aconitine's effect on these processes remains unclear. Materials and methods The effects of aconitine on the inflammation, apoptosis and viability of H9c2 rat cardiomyocytes were evaluated by flow cytometry, Western blot, RNA sequencing and bioinformatics analysis. Results Aconitine suppressed cardiomyocyte proliferation and induced inflammation and apoptosis in a dose- and time-dependent manner. These inflammatory damages could be reversed by a TNF alpha inhibitor and bnip3-mediated mitophagy. Consistent with the in vitro results, overexpression of bnip3 in heart tissue partially suppressed the cardiotoxicity of aconitine by inhibiting apoptosis and the NLRP3 inflammasome. Conclusions Our findings lay a foundation for the application of a TNF alpha inhibitor and bnip3 to aconitine-induced cardiac toxicity prevention and therapy, thereby demonstrating potential for further investigation.

关键词： aconitine bnip3 cardiomyocyte mitophagy

来源：评论

学校读者我要写书评

暂无评论

The pro-cell death Bcl-2 family member, bnip3, is localized to the nucleus of human glial cells: Implications for glioblastoma multiforme tumor cell survival under hypoxia

引用

INTERNATIONAL JOURNAL OF CANCER 2006年第7期118卷 1660-1669页

作者： Burton, TR Henson, ES Baijal, P Eisenstat, DD Gibson, SB Univ Manitoba Manitoba Inst Cell Biol Winnipeg MB R3E 0V9 Canada Univ Manitoba Dept Biochem & Med Genet Winnipeg MB Canada Univ Manitoba Dept Pediat & Child Hlth Winnipeg MB Canada Univ Manitoba Dept Human Anat & Cell Sci Winnipeg MB Canada

The Bcl-2 nineteen kilodalton interacting protein 3 (bnip3) is a hypoxia-inducible proapoptotic member of the Bcl-2 family that induces cell death by associating with the mitochondria. Under normal conditions, bnip3 is expressed in skeletal muscle and in the brain at low levels. In many human solid tumors, bnip3 is upregulated in hypoxic regions but paradoxically, this bnip3 expression fails to induce cell death. Herein, we have determined that bnip3 is primarily localized to the nucleus of glial cells of the normal human brain, as well as in the malignant glioma cell line U251. Upon exposure of U251 cells to hypoxia, bnip3 expression in the cytoplasm increases and localizes with the mitochondria, contributing to induction of cell death. In contrast, when bnip3 is forcibly over expressed in the nucleus, it fails to induce cell death. Expression of N-terminal bnip3 (lacking the transmembrane and conserved domains) in U251 cells blocks hypoxia-induced cell death acting as a dominant negative protein by binding to wildtype bnip3 and blocking its association with the mitochondria. In glioblastoma multiforme (GBM) tumors, bnip3 expression is increased in hypoxic regions of the tumor and is primarily localized to the nucleus in similar to 80% of tumors. Hence, bnip3 is sequestered in the nucleus within the brain but under hypoxic conditions, bnip3 becomes primarily cytoplasmic, promoting cell death. In GBMs, bnip3 expression is increased but it remains sequestered in the nucleus in hypoxic regions, thereby blocking bnip3's ability to associate with the mitochondria, providing tumor cells with a possible survival advantage. (c) 2005 Wiley-Liss, Inc.

关键词： bnip3 astrocytes glial cells glioblastoma multiforme hypoxia mitochondria cell death nuclear localization

来源：评论

学校读者我要写书评

暂无评论

Hyperoside protects against hypoxia/reoxygenation induced injury in cardiomyocytes by suppressing the bnip3 expression

引用

GENE 2017年 629卷 86-91页

作者： Xiao, Rui Xiang, An-Li Pang, Hong-Bo Liu, Ke-Qiang Hubei Prov Hosp Integrated Chinese & Western Med Wuhan 430015 Hubei Peoples R China Tianjin Univ Tradit Chinese Med Tianjin 300193 Peoples R China Wuhan Univ Sci & Technol City Coll Wuhan 430083 Hubei Peoples R China Tianjin Union Med Ctr Tianjin 300191 Peoples R China

Aims: Role of hyperoside in protecting cardiomyocytes from ischemia/reperfusion induced injury has been proved. However, possible protecting mechanisms remain unclear. To fix the problem, an essential pro-apoptotic protein bnip3 was studied in our experiments. Methods and results: Neonatal rat cardiomyocytes were used and submitted to hypoxia for 8 h followed by re oxygenation for 2 h to simulate the ischemia/reperfusion injury. Hypoxia/reoxygenation(H/R) induced damage to cardiomyocytes and the protective effect of hyperoside were examined by means of MTT assay. H/R-induced apoptosis was assessed by Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling(TUNEL) and DNA Ladder assay. mRNA expression of bnip3 was determined by use of quantitative real-time reverse transcription polymerase chain reaction assay. Protein levels of bnip3, Bax, Bcl-2 and cleaved caspase-3 *** using western-blot assay. Our results showed that H/R caused great damage to cardiomyocytes, upregulated the protein expressions of bnip3, Bax, cleaved caspase3, and decreased the expression of the antiapoptotic protein of Bcl-2. Whereas, compared with the H/R group, a decrease in activities of bnip3, Bax, cleaved caspase3, and a promoting expression of Bcl-2 were detected in the H/R goup pretreated with hyperoside. Conclusion: It was concluded in our study that H/R-induced apoptotic effect in cardiomyocytes could be attenuated by hyperoside, and the protective role of hyperoside, if not completely, could be partly through the suppression of the pro-apoptotic gene bnip3.

关键词： Hyperoside Hypoxia/reoxygenation Apoptosis bnip3

来源：评论

学校读者我要写书评

暂无评论

Association between HIF-1α, bnip3, and autophagy in the chorionic villi of missed abortion

引用

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 2023年第7期49卷 1710-1716页

作者： Kou, Junna Yuan, Enwu Yan, Guangwei Zhengzhou Univ Affiliated Hosp 1 Dept Pathol Zhengzhou Henan Peoples R China Zhengzhou Univ Affiliated Hosp 3 Dept Clin Lab Zhengzhou Henan Peoples R China Zhengzhou Univ Affiliated Hosp 3 Dept Pathol Zhengzhou Henan Peoples R China Zhengzhou Univ Affiliated Hosp 3 Dept Pathol 7 Kangfu St Zhengzhou Peoples R China

Aim: To investigate the expression of autophagy mediated by the hypoxiainducible factor 1 alpha (HIF-1 alpha)/bnip3 signaling pathway in villus tissues of missed abortion and HTR-8/SVneo cells and to elucidate the association of HIF-1 alpha and bnip3 in autophagy of missed abortion. Methods: Villus tissues from 30 healthy women with induced abortion and 35 patients with missed abortion were collected, and HTR-8/SVneo cells were cultured under hypoxia and transfected with HIF-1 alpha-siRNA. Real-time polymerase chain reaction was utilized to measure the mRNA levels of HIF-1 alpha and bnip3;Western blotting was performed to determine the protein levels of HIF-1 alpha, bnip3, LC3 II/I, and Beclin 1 in villus tissues and HTR-8/SVneo cells. Cellular invasion activity was detected by transwell matrigel assay. The level of autophagy was confirmed by transmission electron microscopy of autophagosome formation. Results: The mRNA levels of HIF-1 alpha and bnip3 were significantly lower in the missed abortion villi than in the induced abortion samples. The protein levels of HIF-1 alpha, bnip3, Beclin 1, and LC3II/I were significantly decreased in villus tissues from missed abortion, and autophagosomes were significantly decreased in villus tissues from missed abortion. Under hypoxia, the mRNA expression of HIF-1 alpha and bnip3 was inhibited after silencing HIF-1a by RNAi, while the protein expression of HIF-1 alpha, bnip3, Beclin1, and LC3II/I was significantly downregulated. The number of invading cells was significantly decreased, and autophagosomes were significantly decreased after silencing HIF-1 alpha by RNAi in HTR-8/SVneo cells. Conclusions: Autophagy mediated by the HIF-1 alpha/bnip3 signaling pathway in villous trophoblast cells may be associated with the progression and development of missed abortion.

关键词： autophagy bnip3 HIF-1 alpha HTR-8 SVneo missed abortion

来源：评论

学校读者我要写书评

暂无评论

KPNB1-ATF4 induces bnip3-dependent mitophagy to drive odontoblastic differentiation in dental pulp stem cells

引用

CELLULAR & MOLECULAR BIOLOGY LETTERS 2024年第1期29卷 145页

作者： Zhang, Zeying Yang, Di Yan, Xiaoyuan Qiu, Qiujing Guo, Jiajie Qiu, Lihong China Med Univ Sch & Hosp Stomatol Dept Endodont Liaoning Prov Key Lab Oral Dis 117 Nanjing North St Shenyang 110002 Liaoning Peoples R China

Background Differentiating dental pulp stem cells (DPSCs) into odontoblasts is a critical process for tooth self-repair and dentine-pulp engineering strategies in the clinic. However, the mechanism underlying the regulation of DPSC odontoblastic differentiation remains largely unknown. Here, we demonstrated that BCL-2 interacting protein 3 (bnip3)-dependent mitophagy is associated with importin subunit beta-1 (KPNB1)-activating transcription factor 4 (ATF4), which promotes DPSC odontoblastic differentiation. Methods The key genes involved in DPSC odontogenic differentiation were identified via bioinformatics. Stable silencing or overexpression of bnip3 was performed to investigate its impact on DPSC differentiation in vitro (n >= 3). To explore the role of bnip3 in vivo, tooth root fragments loaded with the hydrogel-transfected DPSC complex were implanted into nude mice (n >= 6). Dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) polymerase chain reaction (PCR) were conducted to explore the binding site of ATF4 to the bnip3 promoter (n >= 3). Mitochondrial function experiments were performed to investigate the impact of ATF4-bnip3 on mitochondria (n >= 3). Immunoprecipitation (IP) mass spectrometry (MS) was used to investigate the interaction between ATF4 and its binding protein, KPNB1. Plasmids containing wild-type (WT)/mutant (MUT)-nuclear localization signal (NLS) forms of ATF4 were constructed to determine the specific amino acid residues recognized by KPNB1 and their effects on DPSC odontoblastic differentiation (n >= 3). Results Compared with those in the control group, the levels of autophagy and mitophagy, especially bnip3-dependent mitophagy, were greater in the DPSC odontoblastic differentiation group (P < 0.05). Genetic silencing or overexpression of bnip3 demonstrated that bnip3 expression was positively correlated with the transition of DPSCs into odontoblasts both in vitro and in vivo (P < 0.05). ATF4 regulates the expression of B

关键词： Dental pulp stem cell Odontoblastic differentiation Mitophagy ATF4 bnip3 KPNB1

来源：评论

学校读者我要写书评

暂无评论

Autophagic digestion of Leishmania major by host macrophages is associated with differential expression of bnip3, CTSE, and the miRNAs miR-101c, miR-129, and miR-210

引用

PARASITES & VECTORS 2015年第1 p404-404期8卷 1-31页

作者： Frank, Benjamin Marcu, Ana de Oliveira Almeida Petersen, Antonio Luis Weber, Heike Stigloher, Christian Mottram, Jeremy C. Scholz, Claus Juergen Schurigt, Uta Univ Wurzburg Inst Mol Infect Biol D-97080 Wurzburg Germany Univ Glasgow Inst Infect Immun & Inflammat Wellcome Trust Ctr Mol Parasitol Glasgow G12 8TA Lanark Scotland Fundacao Oswaldo Cruz BA Lab Patol & Biointervencao Salvador BA Brazil Univ Wurzburg Interdisciplinary Ctr Clin Res IZKF D-97080 Wurzburg Germany Univ Wurzburg Bioctr Div Electron Microscopy D-97080 Wurzburg Germany

Background: Autophagy participates in innate immunity by eliminating intracellular pathogens. Consequently, numerous microorganisms have developed strategies to impair the autophagic machinery in phagocytes. In the current study, interactions between Leishmania major (L. m.) and the autophagic machinery of bone marrow-derived macrophages (BMDM) were analyzed. Methods: BMDM were generated from BALB/c mice, and the cells were infected with L. m. promastigotes. Transmission electron microscopy (TEM) and electron tomography were used to investigate the ultrastructure of BMDM and the intracellular parasites. Affymetrix (R) chip analyses were conducted to identify autophagy-related messenger RNAs (mRNAs) and microRNAs (miRNAs). The protein expression levels of autophagy related 5 (ATG5), BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (bnip3), cathepsin E (CTSE), mechanistic target of rapamycin (MTOR), microtubule-associated proteins 1A/1B light chain 3B (LC3B), and ubiquitin (UB) were investigated through western blot analyses. BMDM were transfected with specific small interfering RNAs (siRNAs) against autophagy-related genes and with mimics or inhibitors of autophagy-associated miRNAs. The infection rates of BMDM were determined by light microscopy after a parasite-specific staining. Results: The experiments demonstrated autophagy induction in BMDM after in vitro infection with L. m.. The results suggested a putative MTOR phosphorylation-dependent counteracting mechanism in the early infection phase and indicated that intracellular amastigotes were cleared by autophagy in BMDM in the late infection phase. Transcriptomic analyses and specific downregulation of protein expression with siRNAs suggested there is an association between the infection-specific over expression of bnip3, as well as CTSE, and the autophagic activity of BMDM. Transfection with mimics of mmu-miR-101c and mmu-miR-129-5p, as well as with an inhibitor of mmu-miR-210-5p, demonstrated direct ef

关键词： Autophagy bnip3 CTSE Electron tomography Leishmania major Macrophages miRNAs MTOR siRNAs Transmission electron microscopy

来源：评论

学校读者我要写书评

暂无评论

Increased bnip3 and decreased mutant p53 in cisplatin-sensitive PDT-resistant HT29 cells

引用

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2005年第2期331卷 648-657页

作者： Zacal, N Espiritu, M Singh, G Rainbow, AJ Juravinski Canc Ctr Hamilton ON Canada McMaster Univ Dept Biol Hamilton ON Canada McMaster Univ Dept Pathol & Mol Med Hamilton ON Canada

We have reported previously the isolation of three photodynamic therapy (PDT)-resistant human colon carcinoma HT29 cell lines that shorn increased expression of the Hsp27 and bnip3 protein and a decreased expression of the mutant p53 protein compared to parental HT29 cells. Since Mutant p53 and increased expression of Hsp27 liar c been associated with resistance to various chemotherapeutic agents. whereas bnip3 is a potent inducer of apoptosis, we were interested in determining whether these PDT-resistant cells were cross-resistant to other cytotoxic agents. We report here that the PDT-resistant HT29 cell lines showed a significant increase in cisplatin sensitivity and an increase in both Spontaneous and cisplatin-induced apoptosis compared to parental HT29 cells. In addition. the cisplatin sensitivity of the PDT-resistant HT29 variants and several other clonal variants of HT29 cells correlated with increased bnip3 and decreased mutant p53 protein levels. but not Hsp27 protein levels, (c) 2005 Elsevicr Inc. All rights reserved.

关键词： PDT resistance cisplatin sensitvity bnip3 p53 Hsp27 HT29 cells apoptosis

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：