检索结果-内蒙古大学图书馆

Nitric oxide induces bnip3 expression that causes cell death in macrophages

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2004年第2期321卷 298-305页

作者： Yook, YH Kang, KH Maeng, O Kim, TR Lee, HO Kang, KI Kim, YS Paik, SG Lee, H Chungnam Natl Univ Dept Biol Taejon South Korea Chungnam Natl Univ Inst Biotechnol Taejon South Korea Korea Adv Inst Sci & Technol Dept Chem Taejon 305701 South Korea Chungnam Natl Univ Dept Biochem Taejon South Korea

Nitric oxide (NO) is involved in many physiological processes and also causes pathological effects by inducing apoptosis. It can enhance or suppress apoptosis depending on its concentration and the cell type involved. In this report, we used cDNA microarray analysis to show that SNAP, an NO donor, strongly induces Bcl-2/adenovirus EIB 19kDa-interacting protein 3 (bnip3) in macrophages. bnip3 is a mitochondrial pro-apoptotic protein that contains a Bcl-2 homology 3 domain and a COOH-terminal transmembrane (TM) domain. Macrophages activated by LPS/IFN-gamma produce nitric oxide synthase 2 (NOS2) and release endogenous NO. Expression of bnip3 was also induced in macrophages by LPS/IFN-gamma, and the induction was blocked by a NOS2 inhibitor, S-methyl-isothiourea. Peritoneal macrophages from NOS2-null mice failed to produce bnip3 in response to LPS/IFN-gamma. We conclude that bnip3 expression in macrophages is controlled by the intracellular level of nitric oxide. Overexpression of bnip3 but not of bnip3 DeltaTM, a bnip3 mutant without the TM domain and C-terminal tail, led to apoptosis of the cells. Promoter analysis showed that the region between -281 and -1 of the 5-upstream enhancer region of murine bnip3 was sufficient for NO-dependent expression of bnip3. (C) 2004 Elsevier Inc. All rights reserved.

关键词： apoptosis macrophage bnip3 nitric oxide

来源：评论

学校读者我要写书评

暂无评论

Par-4 regulates autophagic cell death in human cancer cells via upregulating p53 and bnip3

引用

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 2020年第7期1867卷 118692-118692页

作者： Thayyullathil, Faisal Cheratta, Anees Rahman Pallichankandy, Siraj Subburayan, Karthikeyan Tariq, Saeed Rangnekar, Vivek M. Galadari, Sehamuddin New York Univ Cell Death Signaling Lab Div Sci Biol Expt Res BldgPOB 129188Saadiyat Isl Campus Abu Dhabi U Arab Emirates UAE Univ Coll Med & Hlth Sci Dept Anat POB 17666 Al Ain U Arab Emirates Univ Kentucky Dept Radiat Med Lexington KY 40536 USA Univ Kentucky Markey Canc Ctr Lexington KY 40536 USA

Prostate apoptosis response-4 (Par-4) is a tumor suppressor protein that selectively induces apoptosis in cancer cells. Although the mechanism of Par-4-mediated induction of apoptosis has been well studied, the involvement of Par-4 in other mechanisms of cell death such as autophagy is unclear. We investigated the mechanism involved in Par-4-mediated autophagic cell death in human malignant glioma. We demonstrate for the first time that the tumor suppressor lipid, ceramide (Cer), causes Par-4 induction, leading to autophagic cell death in human malignant glioma. Furthermore, we identified the tumor suppressor protein p53 and BCL2/adenovirus E1B 19 kDa interacting protein 3 (bnip3) as downstream targets of Par-4 during Cer-mediated autophagic cell death. RNAi-mediated down-regulation of Par-4 blocks Cer-induced p53-bnip3 activation and autophagic cell death, while upregulation of Par-4 augmented p53-bnip3 activation and autophagic cell death. Remarkably, in many instances, Par-4 overexpression alone was sufficient to induce cell death which is associated with features of autophagy. Interestingly, similar results were seen when glioma cells were exposed to classical autophagy inducers such as serum starvation, arsenic trioxide, and curcumin. Collectively, the novel Par-4-p53-bnip3 axis plays a crucial role in autophagy-mediated cell death in human malignant glioma.

关键词： Autophagy bnip3 Ceramide LC3-II p53 Par-4

来源：评论

学校读者我要写书评

暂无评论

Arsenic trioxide induces autophagic cell death in malignant glioma cells by upregulation of mitochondrial cell death protein bnip3

引用

ONCOGENE 2005年第6期24卷 980-991页

作者： Kanzawa, T Zhang, L Xiao, LC Germano, IM Kondo, Y Kondo, S Univ Texas MD Anderson Canc Ctr Dept Neurosurg Unit 64 Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Biostat Houston TX 77030 USA Mt Sinai Sch Med Dept Neurosurg New York NY 10510 USA

Arsenic trioxide (As2O3) has shown considerable efficacy in treating hematological malignancies with induction of programmed cell death (PCD) type I, apoptosis. However, the mechanisms underlying the antitumor effect of As2O3 on solid tumors are poorly defined. Previously, we reported that As2O3 induced autophagic cell death (PCD type II) but not apoptosis in human malignant glioma cell lines. The purpose of this study was to elucidate the molecular pathway leading to autophagic cell death. In this study, we demonstrated that the cell death was accompanied by involvement of autophagy-specific marker, microtubule-associated protein light chain 3 (LC3), and damage of mitochondrial membrane integrity, but not by caspase activation. Analysis by cDNA microarray, RT-PCR, and Western blot showed that cell death members of Bcl-2 family, Bcl-2/adenovirus E1B 19-kDa- interacting protein 3 (bnip3) and its homologue bnip3-like (bnip3L), were upregulated in As2O3-induced autophagic cell death. Exogenous expression of bnip3, but not bnip3L, induced autophagic cell death in malignant glioma cells without As2O3 treatment. When upregulation of bnip3 induced by As2O3 was suppressed by a dominant-negative effect of the transmembrane-deleted bnip3 (bnip3DTM), autophagic cell death was inhibited. In contrast, bnip3 transfection augmented As2O3-induced autophagic cell death. These results suggest that bnip3 plays a central role in As2O3-induced autophagic cell death in malignant glioma cells. This study adds a new concept to characterize the pathways by which As2O3 acts to induce autophagic cell death in malignant glioma cells.

关键词： arsenic trioxide autophagy bnip3 glioma LC3

来源：评论

学校读者我要写书评

暂无评论

Cellular redox status determines sensitivity to bnip3-mediated cell death in cardiac myocytes

引用

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY 2015年第12期308卷 C983-C992页

作者： Lee, Youngil Kubli, Dieter A. Hanna, Rita A. Cortez, Melissa Q. Lee, Hwa-Youn Miyamoto, Shigeki Gustafsson, Asa B. Univ Calif San Diego Skaggs Sch Pharm & Pharmaceut Sci La Jolla CA 92093 USA Univ Calif San Diego Dept Pharmacol La Jolla CA 92093 USA

The atypical BH3-only protein Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (bnip3) is an important regulator of hypoxia-mediated cell death. Interestingly, the susceptibility to bnip3-mediated cell death differs between cells. In this study we examined whether there are mechanistic differences in bnip3-mediated cell death between neonatal and adult cardiac myocytes. We discovered that bnip3 is a potent inducer of cell death in neonatal myocytes, whereas adult myocytes are remarkably resistant to bnip3. When exploring the potential underlying basis for the resistance, we discovered that adult myocytes express significantly higher levels of the mitochondrial antioxidant manganese superoxide dismutase (MnSOD) than neonatal myocytes. Overexpression of MnSOD confers resistance to bnip3-mediated cell death in neonatal myocytes. In contrast, the presence of a pharmacological MnSOD inhibitor, 2-methoxyestradiol, results in increased sensitivity to bnip3-mediated cell death in adult myocytes. Cotreatment with the mitochondria-targeted antioxidant MitoTEMPO or the MnSOD mimetic manganese (III) tetrakis (4-benzoic acid) porphyrin chloride abrogates the increased cell death by 2-methoxyestradiol. Moreover, increased oxidative stress also restores the ability of bnip3 to induce cell death in adult myocytes. Taken together, these data indicate that redox status determines cell susceptibility to bnip3-mediated cell death. These findings are clinically relevant, given that pediatric hearts are known to be more vulnerable than the adult heart to ischemic injury. Our studies provide important insight into why pediatric hearts are more sensitive to ischemic injury and may help in the clinical management of childhood heart disease.

关键词： bnip3 cardiac myocytes mitochondria autophagy apoptosis oxidative stress

来源：评论

学校读者我要写书评

暂无评论

Akebia saponin D alleviates hepatic steatosis through bnip3 induced mitophagy

引用

JOURNAL OF PHARMACOLOGICAL SCIENCES 2018年第4期136卷 189-195页

作者： Gong, Li-li Yang, Song Zhang, Wen Han, Fei-fei Lv, Ya-li Wan, Zi-Rui Liu, He Jia, Yang-jie Xuan, Ling-ling Liu, Li-hong Capital Med Univ Beijing Chao Yang Hosp 8 Gongren Tiyuchang Nanlu Beijing 100020 Peoples R China

Akebia Saponin D (ASD) is the most abundant constituent of the rhizome of Dipsacus asper Wall. The prior studies have shown that ASD alleviates hepatic steatosis targeted at the modulation of autophagy and exerts hepatoprotective effects through mitochondria. However, it is still unclear which signal transduction pathway that ASD increase autophagy and protect the mitochondria. The purpose of this paper was to explore the mechanisms through which ASD alleviates hepatic steatosis. ASD significantly reduced lipid accumulation in BRL cells. Furthermore, ASD significantly increased the mitophagy acting as increase the colocalization between mitochondria and punctate EGFP-LC3. ASD treatment increased the expression of bnip3, phospho-AMPK, prevented oleic acid (OA) induced LC3-II and phospho-mTOR expression. These effects were similar to the effects cotreatment with rapamycin. ASD treatment could not attenuate the expression of bnip3 blocked by chloroquine (CQ) or siRNA-mediated knockdown of bnip3. These results suggest that Akebia saponin D alleviates hepatic steatosis targeted at bnip3 mediated mitophagy. Activation of bnip3 via ASD may offer a new strategy for treating NAFLD. (C) 2018 The Authors. Production and hosting by Elsevier B.V.

关键词： bnip3 Mitophagy NAFLD Akebia saponin D

来源：评论

学校读者我要写书评

暂无评论

Enhancing lysosome biogenesis attenuates bnip3-induced cardiomyocyte death

引用

AUTOPHAGY 2012年第3期8卷 297-309页

作者： Ma, Xiucui Godar, Rebecca J. Liu, Haiyan Diwan, Abhinav Washington Univ Sch Med Dept Internal Med Ctr Cardiovasc ResDiv Cardiol St Louis MO 63110 USA John Cochran VA Med Ctr St Louis MO USA

Hypoxia-inducible pro-death protein bnip3 (BCL-2/adenovirus E1B 19-kDa interacting protein 3), provokes mitochondrial permeabilization causing cardiomyocyte death in ischemia-reperfusion injury. Inhibition of autophagy accelerates bnip3-induced cell death, by preventing removal of damaged mitochondria. We tested the hypothesis that stimulating autophagy will attenuate bnip3-induced cardiomyocyte death. Neonatal rat cardiac myocytes (NRCMs) were adenovirally transduced with bnip3 (or LacZ as control;at multiplicity of infection = 100);and autophagy was stimulated with rapamycin (100 nM). Cell death was assessed at 48 h. bnip3 expression increased autophagosome abundance 8-fold and caused a 3.6-fold increase in cardiomyocyte death as compared with control. Rapamycin treatment of bnip3-expressing cells led to further increase in autophagosome number without affecting cell death. bnip3 expression led to accumulation of autophagosome-bound LC3-II and p62, and an increase in autophagosomes, but not autolysosomes (assessed with dual fluorescent mCherry-GFP-LC3 expression). bnip3, but not the transmembrane deletion variant, interacted with LC3 and colocalized with mitochondria and lysosomes. However, bnip3 did not target to lysosomes by subcellular fractionation, provoke lysosome permeabilization or alter lysosome pH. Rather, bnip3-induced autophagy caused a decline in lysosome numbers with decreased expression of the lysosomal protein LAMP-1, indicating lysosome consumption and consequent autophagosome accumulation. Forced expression of transcription factor EB (TFEB) in bnip3-expressing cells increased lysosome numbers, decreased autophagosomes and increased autolysosomes, prevented p62 accumulation, removed depolarized mitochondria and attenuated bnip3-induced death. We conclude that bnip3 expression induced autophagosome accumulation with lysosome consumption in cardiomyocytes. Forced expression of TFEB, a lysosomal biogenesis factor, restored autophagosome processing an

关键词： bnip3 autophagy cardiomyocyte death lysosomes TFEB

来源：评论

学校读者我要写书评

暂无评论

The role of Bcl-2 family member bnip3 in cell death and disease: NIPping at the heels of cell death

引用

CELL DEATH AND DIFFERENTIATION 2009年第4期16卷 515-523页

作者： Burton, T. R. Gibson, S. B. Manitoba Inst Cell Biol Winnipeg MB R3E 0V9 Canada Univ Manitoba Dept Biochem & Med Genet Winnipeg MB Canada

Bcl-2 nineteen-kilodalton interacting protein (bnip3) is a BH-3-only Bcl-2 family member whose expression levels increase during stress such as hypoxia through hypoxia-inducing factor-1-dependent or -independent mechanisms. When bnip3 expression is induced, it localizes to the mitochondria and triggers a loss of membrane potential, and an increase in the reactive oxygen species production, which often leads to cell death. Cells under normal growth conditions suppress bnip3 expression through transcriptional repression. There is considerable debate in the literature regarding what type of cell death is induced by bnip3. It has been observed that bnip3 could induce necrosis, autophagy and/or apoptosis. In contrast, other studies indicate that bnip3 could promote cell survival. Besides its cell death regulation, bnip3 plays a key role in the pathogenicity of many diseases. In cardiac infarction, loss of bnip3 expression has been shown to reduce the number of damaged cardiomyocytes after ischemia and reperfusion. bnip3 expression also plays an important role in the deregulation of cell death in many cancers. In this review, we will discuss the different and often contradictory mechanisms of bnip3 regulation of cell death and the role that bnip3 may play in diseases.

关键词： bnip3 apoptosis ischemia hypoxia autophagy cancer

来源：评论

学校读者我要写书评

暂无评论

EIF4A3-Induced circ-bnip3 Aggravated Hypoxia-Induced Injury of H9c2 Cells by Targeting miR-27a-3p/bnip3

引用

MOLECULAR THERAPY-NUCLEIC ACIDS 2020年 19卷 533-545页

作者： Li, Yansong Ren, Shuhong Xia, Jingwen Wei, Yong Xi, Yinhua Shanghai Songjiang Dist Ctr Hosp Dept Cardiovasol Shanghai 201600 Peoples R China Xuzhou Cent Hosp Dept Cardiovasol Xuzhou Jiangsu Peoples R China Shanghai Gen Hosp Dept Cardiovasol Shanghai Peoples R China

Acute myocardial infarction (AMI) results from long-term diminished blood supply diminishment (ischemia) to the heart, and the main reason for ischemia is hypoxia. BCL2 interaction protein 3 (bnip3) can be upregulated by hypoxia and participates in the mediation of hypoxia-activated apoptosis in cardiac myocyte death. The purpose of this study was to interrogate the mechanism of bnip3 in hypoxia-activated cardiac myocyte injury. Cell viability and apoptosis were evaluated by Cell counting kit 8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), TdT-mediated dUTP Nick-End Labeling (TUNEL), and caspase-3 activity assays. Molecular interactions were assessed by RNA immunoprecipitation (RIP) and pull-down assays. Gene levels were assessed via quantitative real-time PCR and western blot. bnip3 expression was upregulated by hypoxia in H9c2 cells. We found that circ-bnip3 (hsa_circ_0005972), whose annotated gene was bnip3, was induced by hypoxia and positively regulated bnip3 expression. Knockdown of bnip3 or circ-bnip3 reversed the effect of hypoxia in attenuating H9c2 cell viability and inducing apoptosis. circ-bnip3 sponged miRNA-27a-3p (miR-27a-3p) to upregulate bnip3 expression. Moreover, eukaryotic translation initiation factor 4A3 (EIF4A3) bound with the upstream region of the circ-bnip3 mRNA transcript and induced circ-bnip3 expression in H9c2 cells. EIF4A3-induced circ-bnip3 aggravated hypoxia-caused injury of H9c2 cells through targeting miR-27a-3p/ bnip3 pathway, indicating circ-bnip3 as a new target for relieving hypoxia-induced injury of cardiac myocytes.

关键词： hypoxia-activated injury H9c2 cells circ-bnip3 bnip3 miR-27a-3p

来源：评论

学校读者我要写书评

暂无评论

FoxG1/bnip3 axis promotes mitophagy and blunts cisplatin resistance in osteosarcoma

引用

CANCER SCIENCE 2024年第8期115卷 2565-2577页

作者： Pan, Baolong Li, Yan Han, Huiyun Zhang, Lu Hu, Xuemei Pan, Yanyu Peng, Zhuohui Kunming Med Univ Affiliated Hosp 6 Hlth Examinat Ctr Yuxi Yunnan Peoples R China Yuxi Childrens Hosp Dept Neuroendocrine Yuxi Yunnan Peoples R China Kunming Childrens Hosp Dept Pharm Kunming Yunnan Peoples R China Kunming Med Univ Affiliated Hosp 3 Dept Asset Management Kunming Yunnan Peoples R China Naval Med Univ Coll Basic Med Sci Shanghai Peoples R China Kunming Med Univ Affiliated Hosp 3 Dept Orthoped 2 Kunming Yunnan Peoples R China

Cisplatin (CDDP) is a commonly used chemotherapeutic for osteosarcoma (OS) patients, and drug resistance remains as a major hurdle to undermine the treatment outcome. Here, we investigated the potential involvement of FoxG1 and bnip3 in CDDP resistance of OS cells. FoxG1 and bnip3 expression levels were detected in the CDDP-sensitive and CDDP-resistant OS tumors and cell lines. Mitophagy was observed through transmission electron microscope analysis. The sensitivity to CDDP in OS cells upon FoxG1 overexpression was examined in cell and animal models. We found that FoxG1 and bnip3 showed significant downregulation in the CDDP-resistant OS tumor samples and cell lines. CDDP-resistant OS tumor specimens and cells displayed impaired mitophagy. FoxG1 overexpression promoted bnip3 expression, enhanced mitophagy in CDDP-resistant OS cells, and resensitized the resistant cells to CDDP treatment in vitro and in vivo. Our data highlighted the role of the FoxG1/bnip3 axis in regulating mitophagy and dictating CDDP resistance in OS cells, suggesting targeting FoxG1/bnip3-dependent mitophagy as a potential strategy to overcome CDDP resistance in OS. Cisplatin (CDDP) resistance remains as a major hurdle to osteosarcoma treatment. Here, we uncovered the role of the FoxG1/bnip3 axis in regulating mitophagy and dictating CDDP resistance in osteosarcoma cells, suggesting that targeting FoxG1/bnip3-dependent mitophagy could be a potential strategy to overcome CDDP resistance in ***

关键词： bnip3 cisplatin (CDDP) drug resistance FoxG1 mitophgy osteosarcoma (OS)

来源：评论

学校读者我要写书评

暂无评论

Expression of the gene encoding the pro-apoptotic bnip3 protein and stimulation of hypoxia-inducible factor-1α (HIF-1α) protein following focal cerebral ischernia in rats

引用

NEUROCHEMISTRY INTERNATIONAL 2006年第8期48卷 687-695页

作者： Althaus, J. Bernaudin, M. Petit, E. Toutain, J. Touzani, O. Rami, A. Univ Frankfurt Klinikum Inst Mol & Zellulare Anat D-60590 Frankfurt Germany Univ Caen CNRS UMR 6185 F-14074 Caen France

Hypoxia is a common cause of cell death and is implicated in many disease processes including stroke and chronic degenerative disorders. In response to hypoxia, cells express a variety of genes which allow adaptation to altered metabolic demands, decreased oxygen demands, and the removal of irreversibly damaged cells. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates the adaptive response to hypoxia in cells. In this study, we reported an early, time-related, gradual up-regulation of HIF-1 alpha, and a moderate increase in vascular endothelial growth factor (VEGF)- and erythropoietin (Epo)-levels following transient focal ischemia. Moreover, we demonstrated, for the first time a specific localization of the pro-apoptotic regulator bnip3 in striatal and cortical neurons after transient focal ischemia in rats. Prolonged intranuclear bnip3 immunoreactivity was associated with delayed neuronal death. Experiments showed protein increases on Western blots of brain tissue with peaks at 48 h after ischemia. Epo responds to ischemia in an early stage, whereas VEGF and bnip3 accumulate in cells at later times after ischemia. This suggests the possibility that BH3-only proteins might be one of the major downstream effectors of HIF-1 alpha in hypoxic cell death. These findings open the possibility that the hypoxia-regulated pro-apoptotic protein bnip3 enters the nucleus and could interact with other proteins involved in DNA structure, transcription or mRNA splicing after focal brain ischemia. (c) 2006 Elsevier Ltd. All rights reserved.

关键词： HIF focal cerebral ischemia rat bnip3 VEGF Epo 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：