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https://www.readbyqxmd.com/read/29338979/dysregulated-autophagy-in-restrictive-cardiomyopathy-due-to-pro209leu-mutation-in-bag3
#1
A Schänzer, S Rupp, S Gräf, D Zengeler, C Jux, H Akintürk, L Gulatz, N Mazhari, T Acker, R Van Coster, B K Garvalov, A Hahn
Myofibrillary myopathies (MFM) are hereditary myopathies histologically characterized by degeneration of myofibrils and aggregation of proteins in striated muscle. Cardiomyopathy is common in MFM but the pathophysiological mechanisms are not well understood. The BAG3-Pro209Leu mutation is associated with early onset MFM and severe restrictive cardiomyopathy (RCM), often necessitating heart transplantation during childhood. We report on a young male patient with a BAG3-Pro209Leu mutation who underwent heart transplantation at eight years of age...
January 6, 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29323723/haplo-insufficiency-of-bcl2-associated-athanogene-3-in-mice-results-in-progressive-left-ventricular-dysfunction-%C3%AE-adrenergic-insensitivity-and-increased-apoptosis
#2
Valerie D Myers, Dhanendra Tomar, Muniswamy Madesh, JuFang Wang, Jianliang Song, Xue-Qian Zhang, Manish K Gupta, Farzaneh G Tahrir, Jennifer Gordon, Joseph M McClung, Christopher D Kontos, Kamel Khalili, Joseph Y Cheung, Arthur M Feldman
Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid protein that is found predominantly in the heart, skeletal muscle and many cancers. Deletions and truncations in BAG3 that result in haplo-insufficiency have been associated with the development of dilated cardiomyopathy. To study the cellular and molecular events attributable to BAG3 haplo-insufficiency we generated a mouse in which one allele of BAG3 was flanked by loxP recombination sites (BAG3fl/+ ). Mice were crossed with α-MHC-Cre mice in order to generate mice with cardiac-specific haplo-insufficiency (cBAG3+/-) and underwent bi-weekly echocardiography to assess their cardiac phenotype...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29316663/modulation-of-protein-quality-control-and-proteasome-to-autophagy-switch-in-immortalized-myoblasts-from-duchenne-muscular-dystrophy-patients
#3
Marion Wattin, Loïc Gaweda, Pascale Muller, Mathieu Baritaud, Charlotte Scholtes, Chloé Lozano, Kathrin Gieseler, Carole Kretz-Remy
The maintenance of proteome integrity is of primary importance in post-mitotic tissues such as muscle cells; thus, protein quality control mechanisms must be carefully regulated to ensure their optimal efficiency, a failure of these processes being associated with various muscular disorders. Duchenne muscular dystrophy (DMD) is one of the most common and severe forms of muscular dystrophies and is caused by mutations in the dystrophin gene. Protein quality control modulations have been diversely observed in degenerating muscles of patients suffering from DMD or in animal models of the disease...
January 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29304346/nrf2-mediates-the-expression-of-bag3-and-autophagy-cargo-adaptor-proteins-and-tau-clearance-in-an-age-dependent-manner
#4
Maoping Tang, Changyi Ji, Susanne Pallo, Irfan Rahman, Gail V W Johnson
During aging, decreased efficiency of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation and autophagic processes in the brain may be a contributing factor in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. Therefore, we analyzed the expression of Bcl-2-associated athanogene 3, a cochaperone that mediates autophagy, and the autophagy adaptors NBR1, NDP52, and sequestosome 1/p62 in the brains of 4-, 8-, and 12-month-old wild-type and Nrf2 knockout (-/-) mice. We also analyzed the levels of total tau and phospho-tau species...
December 9, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29295729/mir-206-inhibits-cell-proliferation-migration-and-invasion-by-targeting-bag3-in-human-cervical-cancer
#5
Yingying Wang, Yongjie Tian
miR-206 and bcl2-associated athanogene 3 (BAG3) have been suggested as important regulators in various cancer types. However, the biological role of miR-206 and BAG3 in cervical cancer (CC) remains unclear. Here, we investigated the expressions and mechanisms of miR-206 and BAG3 in cervical cancer using in vitro and in vivo assays. In the present study, miR-206 expression was expressed at a lower level in CC tissues and cells than adjacent normal tissues and NEEC cells. By contrast, BAG3 mRNA and protein were expressed at higher levels in CC tissues and cells...
January 2, 2018: Oncology Research
https://www.readbyqxmd.com/read/29286112/upregulation-of-bag3-with-apoptotic-and-autophagic-activities-in-maggot-extract%C3%A2-promoted-rat-skin-wound-healing
#6
Jian-Li Dong, Hai-Cao Dong, Liang Yang, Zhe-Wen Qiu, Jia Liu, Hong Li, Li-Xia Zhong, Xue Song, Peng Zhang, Pei-Nan Li, Lian-Jie Zheng
Maggot extract (ME) accelerates rat skin wound healing, however its effect on cell maintenance in wound tissues remains unclear. B‑cell lymphoma (Bcl) 2‑associated athanogene (BAG)3 inhibits apoptosis and promotes autophagy by associating with Bcl‑2 or Beclin 1. Bcl‑2, the downstream effector of signal transducer and activator of transcription 3 signaling, is enhanced in ME‑treated wound tissues, which may reinforce the Bcl‑2 anti‑apoptotic activity and/or cooperate with Beclin 1 to regulate autophagy during wound healing...
December 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29221135/silencing-of-bag3-inhibits-the-epithelial-mesenchymal-transition-in-human-cervical-cancer
#7
Fei Song, Geng Wang, Zhifang Ma, Yuebing Ma, Yingying Wang
Bcl2-associated athanogene 3 (BAG3) has been reported to be involved in aggressive progression of many tumors. In the present study, we examined the expression of BAG3 in human cervical cancer (CC) tissues and investigated the role of BAG3 in SiHa and HeLa cell growth, migration, and invasion. Here, we found that most of CC tissues highly expressed the protein and mRNA of BAG3, while their expression was obviously lower in paired normal tissues (all p<0.001). BAG3 expression was associated with FIGO stage and metastasis (all p<0...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29200947/hspb8-promotes-the-fusion-of-autophagosome-and-lysosome-during-autophagy-in-diabetic-neurons
#8
Xiao-Cheng Li, Qi-Kuan Hu, Ling Chen, Si-Yang Liu, Shi Su, Hong Tao, Lin-Na Zhang, Tao Sun, Lan-Jie He
Although autophagy has been proposed to play an emerging role in diabetic neuropathy, autophagy and its possible role remains unclear. Moreover, only few studies about diabetes have explored the autophagy mediated by heat shock protein beta-8 (HSPB8) and Bcl-2 associated athanogene 3 (BAG3). In the present study, we examined the autophagy induced by high glucose levels in an in vivo rat model of diabetes induced by streptozotocin (STZ) and an in vitro model of retinal ganglion cell-5 (RGC5) cells under high glucose conditions...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29199462/role-of-genetics-in-peripheral-arterial-disease-outcomes-significance-of-limb-salvage-quantitative-locus-1-genes
#9
Emmanuel Okeke, Ayotunde O Dokun
Peripheral artery disease is a major health care problem with significant morbidity and mortality. Humans with peripheral artery disease exhibit two major and differential clinical manifestations - intermittent claudication and critical limb ischemia. Individuals with intermittent claudication or critical limb ischemia have overlapping risk factors and objective measures of blood flow. Hence, we hypothesized that variation in genetic make-up may be an important determinant in the severity of peripheral artery disease...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29174983/comparison-of-hepatic-transcriptome-profiling-between-acute-liver-injury-and-acute-liver-failure-induced-by-acetaminophen-in-mice
#10
Chunmin Li, Yanan Ming, Wenting Hong, Yingyue Tang, Xiaohong Lei, Xiaobo Li, Yimin Mao
Acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure in many countries. In the present study, we developed stable mouse models of acute drug-induced hepatic injury (DILI) and acute drug-induced hepatic failure (DILF) by sub-lethal and lethal APAP injection respectively. The differences in hepatic transcriptome profiling between these two models were compared by RNA sequencing, which were validated by qPCR, western-blot and ELISA. In results, serum IL-6, TNF-a and IL-10 levels are higher in DILF than in DILI...
November 23, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29114069/bag3-directly-stabilizes-hexokinase-2-mrna-and-promotes-aerobic-glycolysis-in-pancreatic-cancer-cells
#11
Ming-Xin An, Si Li, Han-Bing Yao, Chao Li, Jia-Mei Wang, Jia Sun, Xin-Yu Li, Xiao-Na Meng, Hua-Qin Wang
Aerobic glycolysis, a phenomenon known historically as the Warburg effect, is one of the hallmarks of cancer cells. In this study, we characterized the role of BAG3 in aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) and its molecular mechanisms. Our data show that aberrant expression of BAG3 significantly contributes to the reprogramming of glucose metabolism in PDAC cells. Mechanistically, BAG3 increased Hexokinase 2 (HK2) expression, the first key enzyme involved in glycolysis, at the posttranscriptional level...
November 7, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29113311/the-anti-apoptotic-bag3-protein-is-involved-in-braf-inhibitor-resistance-in-melanoma-cells
#12
Luana Guerriero, Giuseppe Palmieri, Margot De Marco, Antonio Cossu, Paolo Remondelli, Mario Capunzo, Maria Caterina Turco, Alessandra Rosati
BAG3 protein, a member of BAG family of co-chaperones, has a pro-survival role in several tumour types. BAG3 anti-apoptotic properties rely on its characteristic to bind several intracellular partners, thereby modulating crucial events such as apoptosis, differentiation, cell motility, and autophagy. In human melanomas, BAG3 positivity is correlated with the aggressiveness of the tumour cells and can sustain IKK-γ levels, allowing a sustained activation of NF-κB. Furthermore, BAG3 is able to modulate BRAFV600E levels and activity in thyroid carcinomas...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29068469/bag3-dependent-expression-of-mcl-1-confers-resistance-of-mutant-kras-colon-cancer-cells-to-the-hsp90-inhibitor-auy922
#13
Chun Yan Wang, Su Tang Guo, Amanda Croft, Xu Guang Yan, Lei Jin, Xu Dong Zhang, Chen Chen Jiang
Past studies have shown that mutant KRAS colon cancer cells are susceptible to apoptosis induced by the HSP90 inhibitor AUY922. Nevertheless, intrinsic and acquired resistance remains an obstacle for the potential application of the inhibitor in the treatment of the disease. Here we report that Mcl-1 is important for survival of colon cancer cells in the presence of AUY922. Mcl-1 was upregulated in mutant KRAS colon cancer cells selected for resistance to AUY922-induced apoptosis. This was due to its increased stability mediated by Bcl-2-associated athanogene domain 3 (BAG3), which was also increased in resistant colon cancer cells by heat shock factor 1 (HSF1) as a result of chronic endoplasmic reticulum (ER) stress...
October 25, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28978976/subcutaneous-adipose-tissue-gene-expression-and-dna-methylation-respond-to-both-short-and-long-term-weight-loss
#14
S Bollepalli, S Kaye, S Heinonen, J Kaprio, A Rissanen, K A Virtanen, K H Pietiläinen, M Ollikainen
BACKGROUND: Few studies have examined both gene expression and DNA methylation profiles in subcutaneous adipose tissue (SAT) during long-term weight loss. Thus molecular mechanisms in weight loss and regain remain elusive. PARTICIPANTS/METHODS: We performed a one-year weight loss intervention on 19 healthy obese participants (mean BMI 34.6 kg/m(2)) and studied longitudinal gene expression (Affymetrix Human Genome U133 Plus 2.0) and DNA methylation (Infinium HumanMethylation450 BeadChip) in SAT at 0, 5 and 12 months...
October 5, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28941726/a-role-of-bag3-in-regulating-snca-%C3%AE-synuclein-clearance-via-selective-macroautophagy
#15
Yu-Lan Cao, Ya-Ping Yang, Cheng-Jie Mao, Xiao-Qi Zhang, Chen-Tao Wang, Jing Yang, Dong-Jun Lv, Fen Wang, Li-Fang Hu, Chun-Feng Liu
Many studies reveal that BAG3 plays a critical role in the regulation of protein degradation via macroautophagy. However, it remains unknown whether BAG3 affects the quality control of α-synuclein (SNCA), a Parkinson's disease-related protein. In this study, we demonstrated the increases of BAG3 expression in the ventral midbrain of SNCA(A53T) transgenic mice and also in MG132-treated PC12 cells overexpressing wild-type SNCA (SNCA(WT)-PC12). Moreover, we showed that BAG3 overexpression was sufficient to enhance the autophagy activity while knockdown of Bag3 reduced it in SNCA(WT)-PC12 cells...
December 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28933591/suppression-of-chrn-endocytosis-by-carbonic-anhydrase-car3-in-the-pathogenesis-of-myasthenia-gravis
#16
Ailian Du, Shiqian Huang, Xiaonan Zhao, Kuan Feng, Shuangyan Zhang, Jiefang Huang, Xiang Miao, Fulvio Baggi, Rennolds S Ostrom, Yanyun Zhang, Xiangjun Chen, Congfeng Xu
Myasthenia gravis is an autoimmune disorder of the neuromuscular junction manifested as fatigable muscle weakness, which is typically caused by pathogenic autoantibodies against postsynaptic CHRN/AChR (cholinergic receptor nicotinic) in the endplate of skeletal muscle. Our previous studies have identified CA3 (carbonic anhydrase 3) as a specific protein insufficient in skeletal muscle from myasthenia gravis patients. In this study, we investigated the underlying mechanism of how CA3 insufficiency might contribute to myasthenia gravis...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28905214/mir-217-5p-induces-apoptosis-by-directly-targeting-prkci-bag3-itgav-and-mapk1-in-colorectal-cancer-cells
#17
Marion Flum, Michael Kleemann, Helga Schneider, Benjamin Weis, Simon Fischer, René Handrick, Kerstin Otte
Apoptosis is a genetically directed process of programmed cell death. A variety of microRNAs (miRNAs), endogenous single-stranded non-coding RNAs of about 22 nucleotides in length have been shown to be involved in the regulation of the intrinsic or extrinsic apoptotic pathways. There is increasing evidence that the aberrant expression of miRNAs plays a causal role in the development of diseases such as cancer. This makes miRNAs promising candidate molecules as therapeutic targets or agents. MicroRNA (miR)-217-5p has been implicated in carcinogenesis of various cancer entities, including colorectal cancer...
September 14, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28864347/role-of-bag3-in-cancer-progression-a-therapeutic-opportunity
#18
REVIEW
Margot De Marco, Anna Basile, Vittoria Iorio, Michelina Festa, Antonia Falco, Bianca Ranieri, Maria Pascale, Gianluca Sala, Paolo Remondelli, Mario Capunzo, Matthew A Firpo, Raffaele Pezzilli, Liberato Marzullo, Pierpaolo Cavallo, Vincenzo De Laurenzi, Maria Caterina Turco, Alessandra Rosati
BAG3 is a multifunctional protein that can bind to heat shock proteins (Hsp) 70 through its BAG domain and to other partners through its WW domain, proline-rich (PXXP) repeat and IPV (Ile-Pro-Val) motifs. Its intracellular expression can be induced by stressful stimuli, while is constitutive in skeletal muscle, cardiac myocytes and several tumour types. BAG3 can modulate the levels, localisation or activity of its partner proteins, thereby regulating major cell pathways and functions, including apoptosis, autophagy, mechanotransduction, cytoskeleton organisation, motility...
August 29, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28859986/kribb11-accelerates-mcl-1-degradation-through-an-hsf1-independent-mule-dependent-pathway-in-a549-non-small-cell-lung-cancer-cells
#19
Min-Jung Kang, Hye Hyeon Yun, Jeong-Hwa Lee
The Bcl-2 family protein, Mcl-1 is known to have anti-apoptotic functions, and depletion of Mcl-1 by cellular stresses favors the apoptotic process. Moreover, Mcl-1 levels are frequently increased in various cancer cells, including non-small cell lung cancer (NSCLC), and is implicated in resistance to conventional chemotherapy and in cancer metastasis. In this study, we demonstrated that KRIBB11 accelerates the proteasomal degradation of Mcl-1 in the NSCLC cell line, A549. While KRIBB11 is an inhibitor of HSF1, we found that KRIBB11 induced Mcl-1 degradation in an HSF1-independent manner...
October 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28808089/bag3-mediated-proteostasis-at-a-glance
#20
REVIEW
Christina Klimek, Barbara Kathage, Judith Wördehoff, Jörg Höhfeld
Cellular and organismal survival depend on the ability to maintain the proteome, even under conditions that threaten protein integrity. BCL2-associated athanogene 3 (BAG3) is essential for protein homeostasis (proteostasis) in stressed cells. Owing to its multi-domain structure, it engages in diverse processes that are crucial for proteome maintenance. BAG3 promotes the activity of molecular chaperones, sequesters and concentrates misfolded proteins, initiates autophagic disposal, and balances transcription, translation and degradation...
August 14, 2017: Journal of Cell Science
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