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Shuxin Liang, Zhigang Song, Yongyan Wu, Yuanpeng Gao, Mingqing Gao, Fayang Liu, Fengyu Wang, Yong Zhang
Mycobacterium tuberculosis poses a significant global health threat. MicroRNAs play an important role in regulating host anti-mycobacterial defense; however, their role in apoptosis-mediated mycobacterial elimination and inflammatory response remains unclear. In this study, we explored the role of microRNA-27b (miR-27b) in murine macrophage responses to M. tuberculosis infection. We uncovered that the TLR-2/MyD88/NF-κB signaling pathway induced the expression of miR-27b and miR-27b suppressed the production of proinflammatory factors and the activity of NF-κB, thereby avoiding an excessive inflammation during M...
April 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Deyuan Zhu, Wenxi Gao, Zhongmin Zhang
In the present study, the aim was to investigate the role of microRNA-1180 (miR-1180) in the growth and apoptosis of prostate cancer, as well as to identify its direct targets. Initially, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to examine the expression of miR-1180 in the prostate cancer tissues and adjacent normal prostate tissues of 30 patients, as well as in DU145 and RWPE-1 cells. Next, DU145 cells were transfected with miR-1180 mimics, and the expression levels of associated proteins were determined by western blot assay...
April 2018: Oncology Letters
Isabelle R Taylor, Bryan M Dunyak, Tomoko Komiyama, Hao Shao, Xu Ran, Victoria A Assimon, Chakrapani Kalyanaraman, Jennifer N Rauch, Matthew P Jacobson, Erik R P Zuiderweg, Jason E Gestwicki
Protein-protein interactions (PPIs) are an important category of putative drug targets. Improvements in high throughput screening (HTS) have significantly accelerated the discovery of inhibitors for some categories of PPIs. However, methods suitable for screening multi-protein complexes (e.g. those composed of three or more different components) have been slower to emerge. Here, we explored an approach that uses reconstituted multi-protein complexes (RMPCs). As a model system, we chose heat shock protein 70 (Hsp70), which is an ATP-dependent molecular chaperone that interacts with co-chaperones, including DnaJA2 and BAG2...
February 2, 2018: Journal of Biological Chemistry
Kyung-Min Yang, Eunjin Bae, Sung Gwe Ahn, Kyoungwha Pang, Yuna Park, Jinah Park, Jihee Lee, Akira Ooshima, Bora Park, Junil Kim, Yunshin Jung, Satoru Takahashi, Joon Jeong, Seok Hee Park, Seong-Jin Kim
Triple-negative breast cancer (TNBC) is considered incurable with currently available treatments, highlighting the need for therapeutic targets and predictive biomarkers. Here, we report a unique role for Bcl-2-associated athanogene 2 (BAG2), which is significantly overexpressed in TNBC, in regulating the dual functions of cathepsin B as either a pro- or anti-oncogenic enzyme. Silencing BAG2 suppresses tumorigenesis and lung metastasis and induces apoptosis by increasing the intracellular mature form of cathepsin B, whereas BAG2 expression induces metastasis by blocking the auto-cleavage processing of pro-cathepsin B via interaction with the propeptide region...
December 5, 2017: Cell Reports
Juha Piltti, Joakim Bygdell, Chengjuan Qu, Mikko J Lammi
The cell-based therapies could be potential methods to treat damaged cartilage tissues. Instead of native hyaline cartilage, the current therapies generate mainly weaker fibrocartilage-type of repair tissue. A correct microenvironment influences the cellular phenotype, and together with external factors it can be used, for example, to aid the differentiation of mesenchymal stem cells to defined types of differentiated adult cells. In this study, we investigated the effect of long-term exposure to 5% low oxygen atmosphere on human chondrosarcoma HCS-2/8 cells...
February 2018: Journal of Cellular Biochemistry
X Y Zhang, S S Hong, M Zhang, Q Q Cai, M X Zhang, C J Xu
The common spread pattern of ovarian cancer is peritoneal implantation. The growth of the shed ovarian cancer cells in the peritoneal cavity is closely related to the tumor microenvironment. Cancer-associated fibroblasts are vital in the tumor microenvironment. It is not clearly defined that the protein expression alters during the activating process of fibroblasts. This study detected the protein alterations in fibroblasts induced by ovarian cancer cells and explored the potential biological relevance through two-dimensional gel electrophoresis and mass spectrometry...
2018: Neoplasma
Bianca Schönbühler, Verena Schmitt, Heike Huesmann, Andreas Kern, Martin Gamerdinger, Christian Behl
The maintenance of cellular proteostasis is dependent on molecular chaperones and protein degradation pathways. Chaperones facilitate protein folding, maturation, and degradation, and the particular fate of a misfolded protein is determined by the interaction of chaperones with co-chaperones. The co-factor CHIP (C-terminus of HSP70-inteacting protein, STUB1) ubiquitinates chaperone substrates and directs proteins to the cellular degradation systems. The activity of CHIP is regulated by two co-chaperones, BAG2 and HSPBP1, which are potent inhibitors of the E3 ubiquitin ligase activity...
December 30, 2016: International Journal of Molecular Sciences
Jamie O Dyer, Arnob Dutta, Madelaine Gogol, Vikki M Weake, George Dialynas, Xilan Wu, Christopher Seidel, Ying Zhang, Laurence Florens, Michael P Washburn, Susan M Abmayr, Jerry L Workman
Mutations that affect myelodysplasia/myeloid leukemia factor (MLF) proteins are associated with leukemia and several other cancers. However, with no strong homology to other proteins of known function, the role of MLF proteins in the cell has remained elusive. Here, we describe a proteomics approach that identifies MLF as a member of a nuclear chaperone complex containing a DnaJ protein, BCL2-associated anthanogene 2, and Hsc70. This complex associates with chromatin and regulates the expression of target genes...
June 30, 2017: Journal of Molecular Biology
Irene L Katzan, Nicolas R Thompson, Ken Uchino, Nancy Foldvary-Schaefer
BACKGROUND: A majority of stroke patients suffer from obstructive sleep apnea (OSA), which can go unrecognized as the current OSA screens do not perform well in stroke patients. The objective of this study is to modify the existing OSA screening tools for use in stroke patients. METHODS: The cohort study consisted of patients who completed the validated OSA STOP screen and underwent polysomnography within one year. Six prediction models were created and sensitivity and specificity of various cut points were calculated...
May 2016: Sleep Medicine
Yuan Jian, Yuling Chen, Chuanying Geng, Nian Liu, Guangzhong Yang, Jinwei Liu, Xin Li, Haiteng Deng, Wenming Chen
Recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) has become a potential therapeutic drug for multiple myeloma (MM). However, the exact targets and resistance mechanisms of rmhTRAIL on MM cells remain to be elucidated. The present study aimed to investigate the target and resistance-related proteins of rmhTRAIL on myeloma cell lines. A TRAIL-sensitive myeloma cell line, RPMI 8226, and a TRAIL-resistance one, U266, were chosen and the differentially expressed proteins between the two cell lines were analyzed prior and subsequent to rmhTRAIL administration by a liquid chromatography-tandem mass spectrometry method...
June 2016: Biomedical Reports
Laurence Booth, Brian Shuch, Thomas Albers, Jane L Roberts, Mehrad Tavallai, Stefan Proniuk, Alexander Zukiwski, Dasheng Wang, Ching-Shih Chen, Don Bottaro, Heath Ecroyd, Iryna O Lebedyeva, Paul Dent
We performed proteomic studies using the GRP78 chaperone-inhibitor drug AR-12 (OSU-03012) as bait. Multiple additional chaperone and chaperone-associated proteins were shown to interact with AR-12, including: GRP75, HSP75, BAG2; HSP27; ULK-1; and thioredoxin. AR-12 down-regulated in situ immuno-fluorescence detection of ATP binding chaperones using antibodies directed against the NH2-termini of the proteins but only weakly reduced detection using antibodies directed against the central and COOH portions of the proteins...
March 15, 2016: Oncotarget
Takashi Fukuzono, Strahil Iv Pastuhov, Okinobu Fukushima, Chun Li, Ayuna Hattori, Shun-ichiro Iemura, Tohru Natsume, Hiroshi Shibuya, Hiroshi Hanafusa, Kunihiro Matsumoto, Naoki Hisamoto
Mutations in LRRK2 are linked to autosomal dominant forms of Parkinson's disease. We identified two human proteins that bind to LRRK2: BAG2 and HSC70, which are known to form a chaperone complex. We characterized the role of their Caenorhabditis elegans homologues, UNC-23 and HSP-1, in the regulation of LRK-1, the sole homologue of human LRRK2. In C. elegans, LRK-1 determines the polarized sorting of synaptic vesicle (SV) proteins to the axons by excluding SV proteins from the dendrite-specific transport machinery in the Golgi...
April 2016: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Juhani V Partanen
INTRODUCTION: Complex repetitive discharges (CRDs) are thought to result from depolarization of a single denervated muscle fiber, followed by ephaptic spread to adjacent fibers. This leads to cyclic spread of the depolarization to produce a recurrent discharge. Another explanation is suggested. METHODS: CRDs were recorded with single and multiple electromyographic needles longitudinal to muscle fibers in 39 neuropathy patients. RESULTS: The mean frequency of CRDs was 26 Hz, mean number of negative spikes was 5...
April 2016: Muscle & Nerve
Dianbo Qu, Ali Hage, Katie Don-Carolis, En Huang, Alvin Joselin, Farzaneh Safarpour, Paul C Marcogliese, Maxime W C Rousseaux, Sarah J Hewitt, Tianwen Huang, Doo-Soon Im, Steve Callaghan, Danielle Dewar-Darch, Daniel Figeys, Ruth S Slack, David S Park
Emerging evidence has demonstrated a growing genetic component in Parkinson disease (PD). For instance, loss-of-function mutations in PINK1 or PARKIN can cause autosomal recessive PD. Recently, PINK1 and PARKIN have been implicated in the same signaling pathway to regulate mitochondrial clearance through recruitment of PARKIN by stabilization of PINK1 on the outer membrane of depolarized mitochondria. The precise mechanisms that govern this process remain enigmatic. In this study, we identify Bcl2-associated athanogene 2 (BAG2) as a factor that promotes mitophagy...
December 18, 2015: Journal of Biological Chemistry
Xuetian Yue, Yuhan Zhao, Juan Liu, Cen Zhang, Haiyang Yu, Jiabei Wang, Tongsen Zheng, Lianxin Liu, Jun Li, Zhaohui Feng, Wenwei Hu
Tumor suppressor p53 is the most frequently mutated gene in tumors. Many mutant p53 (mutp53) proteins promote tumorigenesis through the gain-of-function (GOF) mechanism. Mutp53 proteins often accumulate to high levels in tumors, which is critical for mutp53 GOF. Its underlying mechanism is poorly understood. Here, we found that BAG2, a protein of Bcl-2 associated athanogene (BAG) family, promotes mutp53 accumulation and GOF in tumors. Mechanistically, BAG2 binds to mutp53 and translocates to the nucleus to inhibit the MDM2-mutp53 interaction, and MDM2-mediated ubiquitination and degradation of mutp53...
August 13, 2015: ELife
Cesar Augusto Dias de Paula, Fernando Enrique Santiago, Adriele Silva Alves de Oliveira, Fernando Augusto Oliveira, Maria Camila Almeida, Daniel Carneiro Carrettiero
Inclusions of phosphorylated tau (p-tau) are a hallmark of many neurodegenerative disorders classified as "tauopathy," of which Alzheimer's disease is the most prevalent form. Dysregulation of tau phosphorylation disrupts neuron structure and function, and hyperphosphorylated tau aggregates to form neurotoxic inclusions. The abundance of ubiquitin in tau inclusions suggests a defect in ubiquitin-mediated tau protein degradation by the proteasome. Under the temperature of 37 °C, the co-chaperone BAG2 protein targets phosphorylated tau for degradation via by a more-efficient, ubiquitin-independent pathway...
May 2016: Cellular and Molecular Neurobiology
Fernando E Santiago, Maria Camila Almeida, Daniel C Carrettiero
Amyloid-beta (Aβ) binds to various neuronal receptors and elicits a context- and dose-dependent toxic or trophic response from neurons. The molecular mechanisms for this phenomenon are presently unknown. The cochaperone BAG2 has been shown to mediate important cellular responses to stress, including cell cycle arrest and apoptosis. Here, we use SH-SY5Y neuroblastoma cells to characterize BAG2 expression and regulation and investigate the involvement of BAG2 in Aβ1-42-mediated neurotrophism or neurotoxicity in the context of differentiation...
September 2015: Journal of Molecular Neuroscience: MN
Zhenhai Song, Shuo Xu, Bin Song, Qinghua Zhang
Bcl-2-associated athanogene 2 (BAG2) is an important member in the BAG family which is characterized by their property of interaction with a variety of partners involved in modulating the proliferation/death balance. The role of BAG family proteins in Parkinson's disease (PD) has not been elucidated. In this study, we demonstrated that overexpressing BAG2 ameliorates the effects of 1-methyl-4-phenylpyridinium (MPP+) in mitochondrial membrane potential (MMP) collapse, reactive oxygen species (ROS) generation, and mitochondrial release of cytochrome C...
March 2015: Journal of Molecular Neuroscience: MN
M Selmansberger, A Feuchtinger, L Zurnadzhy, A Michna, J C Kaiser, M Abend, A Brenner, T Bogdanova, A Walch, K Unger, H Zitzelsberger, J Hess
A substantial increase in papillary thyroid carcinoma (PTC) among children exposed to the radioiodine fallout has been one of the main consequences of the Chernobyl reactor accident. Recently, the investigation of PTCs from a cohort of young patients exposed to the post-Chernobyl radioiodine fallout at very young age and a matched nonexposed control group revealed a radiation-specific DNA copy number gain on chromosomal band 7q11.23 and the radiation-associated mRNA overexpression of CLIP2. In this study, we investigated the potential role of CLIP2 as a radiation marker to be used for the individual classification of PTCs into CLIP2-positive and -negative cases-a prerequisite for the integration of CLIP2 into epidemiological modelling of the risk of radiation-induced PTC...
July 23, 2015: Oncogene
Ravi Goyal, Lawrence D Longo
Exposure to acute high-altitude hypoxia is associated with an increase in cerebral blood flow (CBF) as a consequence of low arterial O2 tension. However, in response to high altitude acclimatization, CBF returns to levels similar to those at sea level, and tissue blood flow is maintained by an increase in angiogenesis. Of consequence, dysregulation of the acclimatization responses and CBF can result in acute mountain sickness, acute cerebral and/or pulmonary edema. To elucidate the signal transduction pathways involved in successful acclimatization to high altitude, in ovine carotid arteries, we tested the hypothesis that high altitude-associated long-term hypoxia results in changes in gene expression of critical signaling pathways...
October 1, 2014: Physiological Genomics
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