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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...
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
Xiang-Qian Che, Bei-Sha Tang, Hong-Feng Wang, Xin-Xiang Yan, Hong Jiang, Lu Shen, Qian Xu, Guang-Hui Wang, Hai-Nan Zhang, Chun-Yu Wang, Ji-Feng Guo
The expansion of a polyglutamine domain in the protein ataxin3 causes spinocerebellar ataxia type-3 (SCA3). However, there is little information to date about the upstream proteins in the ubiquitin-proteasome system of pathogenic ataxin3-80Q. Here, we report that BAG2 (Bcl-2 associated athanogene family protein 2) and BAG5 (Bcl-2-associated athanogene family protein 5) stabilise pathogenic ataxin3-80Q by inhibiting its ubiquitination as determined based on western blotting and co-immunofluorescence experiments...
May 2015: International Journal of Neuroscience
Christian Rogon, Anna Ulbricht, Michael Hesse, Simon Alberti, Preethi Vijayaraj, Diana Best, Ian R Adams, Thomas M Magin, Bernd K Fleischmann, Jörg Höhfeld
Molecular chaperones play key roles during growth, development, and stress survival. The ability to induce chaperone expression enables cells to cope with the accumulation of nonnative proteins under stress and complete developmental processes with an increased requirement for chaperone assistance. Here we generate and analyze transgenic mice that lack the cochaperone HSPBP1, a nucleotide-exchange factor of HSP70 proteins and inhibitor of chaperone-assisted protein degradation. Male HSPBP1(-/-) mice are sterile because of impaired meiosis and massive apoptosis of spermatocytes...
August 1, 2014: Molecular Biology of the Cell
Xiangqian Che, Beisha Tang, Xuejing Wang, Dong Chen, Xinxiang Yan, Hong Jiang, Lu Shen, Qian Xu, Guanghui Wang, Jifeng Guo
Mutations in the PTEN-induced putative kinase 1 (PINK1) gene cause an autosomal recessive form of Parkinson disease (PD). Thus far, little is known about what can regulate the ubiquitin proteasome pathway of PINK1. Here, we reportBAG2(Bcl-2-associated athanogene family protein 2), a member of the BAG family, which directly binds with and stabilises PINK1 by decreasing its ubiquitination. Moreover, we found that BAG2 also binds with the pathogenic R492X PINK1 mutationdirectly and more tightly.Moreover, BAG2 stabilises the R492X PINK1 mutation by decreasing its ubiquitination to a greater extent than the wild-type species...
October 25, 2013: Biochemical and Biophysical Research Communications
Xiangqian Che, Beisha Tang, Xuejing Wang, Dong Chen, Xinxiang Yan, Hong Jiang, Lu Shen, Qian Xu, Guanghui Wang, Jifeng Guo
Mutations in the PTEN-induced putative kinase 1 (PINK1) gene cause an autosomal recessive form of Parkinson disease (PD). Thus far, little is known about what can regulate the ubiquitin proteasome pathway of PINK1. Here, we report BAG2 (Bcl-2-associated athanogene family protein 2), a member of the BAG family, which directly binds with and stabilises PINK1 by decreasing its ubiquitination. Moreover, we found that BAG2 also binds with the pathogenic R492X PINK1 mutation directly and more tightly. Moreover, BAG2 stabilises the R492X PINK1 mutation by decreasing its ubiquitination to a greater extent than the wild-type species...
November 15, 2013: Biochemical and Biophysical Research Communications
Jennifer N Rauch, Jason E Gestwicki
Proteins with Bcl2-associated anthanogene (BAG) domains act as nucleotide exchange factors (NEFs) for the molecular chaperone heat shock protein 70 (Hsp70). There are six BAG family NEFs in humans, and each is thought to link Hsp70 to a distinct cellular pathway. However, little is known about how the NEFs compete for binding to Hsp70 or how they might differentially shape its biochemical activities. Toward these questions, we measured the binding of human Hsp72 (HSPA1A) to BAG1, BAG2, BAG3, and the unrelated NEF Hsp105...
January 17, 2014: Journal of Biological Chemistry
Sachin P Patil, Nhung Tran, Hirosha Geekiyanage, Li Liu, Christina Chan
Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by extracellular deposits of amyloid beta (Aβ) protein and intracellular neurofibrillary tangles of hyperphosphorylated tau protein. Various studies suggest that the tau tangle pathology, which lies downstream to Aβ pathology, is essential to produce AD-associated clinical phenotype and thus treatments targeting tau pathology may prevent or delay disease progression effectively. In this context, our present study examined three polyphenol compounds (curcumin, EGCG and resveratrol) for their possible activity against two endogenous proteins (BAG2 and LAMP1) that are shown to play a vital role in clearing tau tangles from neurons...
October 25, 2013: Neuroscience Letters
Arimantas Lionikas, Colin J Smith, Tracey L Smith, Lutz Bünger, Robert W Banks, Guy S Bewick
Adult muscle size and fibre-type composition are heritable traits that vary substantially between individuals. We used inbred mouse strains in which soleus muscle mass varied by an order of magnitude to explore whether properties of muscle spindles can also be influenced by genetic factors. Skip-serial cross-sections of soleus muscles dissected from 15 male mice of BEH, BEL, C57BL/6J, DUH, LG/J and SM/J strains were analysed for number of muscle spindles and characteristics of intrafusal and extrafusal fibres following ATPase staining...
September 2013: Journal of Anatomy
Shasha Fang, Luhua Li, Boyang Cui, Shuzhen Men, Yuequan Shen, Xue Yang
The recently identified plant Bcl-2-associated athanogene (BAG) family plays an extensive role in plant programmed cell death (PCD) processes ranging from growth and development to stress responses and even cell death. In the Arabidopsis thaliana BAG (AtBAG) protein family, four members (AtBAG1-4) have a domain organization similar to that of mammalian BAG proteins. Here, crystal structures of the BAG domains (BDs) of AtBAG1-4 have been determined; they have high homology and adopt a structure comprising three short parallel α-helices, similar to some mammalian BAG proteins...
June 2013: Acta Crystallographica. Section D, Biological Crystallography
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