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autophagy and heat shock protein

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https://www.readbyqxmd.com/read/28542269/the-small-molecule-kinase-inhibitor-d11-counteracts-17-aag-mediated-up-regulation-of-hsp70-in-brain-cancer-cells
#1
Susanne Schaefer, Tina H Svenstrup, Barbara Guerra
Many types of cancer express high levels of heat shock proteins (HSPs) that are molecular chaperones regulating protein folding and stability ensuring protection of cells from potentially lethal stress. HSPs in cancer cells promote survival, growth and spreading even in situations of growth factors deprivation by associating with oncogenic proteins responsible for cell transformation. Hence, it is not surprising that the identification of potent inhibitors of HSPs, notably HSP90, has been the primary research focus, in recent years...
2017: PloS One
https://www.readbyqxmd.com/read/28465257/5-fluorouracil-targets-histone-acetyltransferases-p300-cbp-in-the-treatment-of-colorectal-cancer
#2
Changzheng Du, Dandan Huang, Yifan Peng, Yunfeng Yao, Ying Zhao, Yang Yang, Haiying Wang, Linlin Cao, Wei-Guo Zhu, Jin Gu
Although 5-fluorouracil (5-FU) is known to interfere with the synthesis of ribonucleic acid and deoxyribonucleic acid, the mechanism underlying its therapeutic efficacy in colorectal cancer (CRC) has not been fully elucidated. We aimed to investigate the influence of 5-FU on histone acetylation, a well-established anti-cancer target, to reveal novel pharmacological effects of 5-FU and their significance for CRC therapy. Results demonstrated that 5-FU induces global histone de-acetylation in multiple CRC cell lines...
April 29, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28457391/cross-talk-between-sirtuin-1-and-high-mobility-box-1-in-steatotic-liver-graft-preservation
#3
M A Zaouali, A Panisello, A Lopez, E Folch, C Castro-Benítez, R Adam, J Roselló-Catafau
BACKGROUND: Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide +-dependent histone deacetylase that regulates various pathways involved in ischemia-reperfusion injury (IRI). Moreover, high-mobility group box 1 protein (HMGB1) has also been involved in inflammatory processes during IRI. However, the roles of both SIRT1 and HMGB1 in liver preservation is poorly understood. In this communication, we evaluated the potential relationship between SIRT1 and HMGB1 in steatotic and non-steatotic liver grafts preserved in Institute Georges Lopez solution (IGL-1) preservation solution enriched or not enriched with trimetazidine (TMZ)...
May 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28442482/a-bag3-coding-variant-in-mice-determines-susceptibility-to-ischemic-limb-muscle-myopathy-by-directing-autophagy
#4
Joseph M McClung, Timothy J McCord, Terence E Ryan, Cameron A Schmidt, Thomas D Green, Kevin W Southerland, Jessica L Reinardy, Sarah B Mueller, Talaignair N Venkatraman, Christopher D Lascola, Sehoon Keum, Douglas A Marchuk, Espen E Spangenburg, Ayotunde O Dokun, Brian H Annex, Christopher D Kontos
Background -Critical limb ischemia (CLI) is a manifestation of peripheral artery disease (PAD) that carries significant mortality and morbidity risk in humans, although its genetic determinants remain largely unknown. We previously discovered two overlapping quantitative trait loci (QTL) in mice, Lsq-1 and Civq-1, that affected limb muscle survival and stroke volume following femoral artery or middle cerebral artery ligation, respectively. Here we report that a Bag3 variant (Ile81Met) segregates with tissue protection from hindlimb ischemia (HLI)...
April 25, 2017: Circulation
https://www.readbyqxmd.com/read/28438108/17-aag-and-apoptosis-autophagy-and-mitophagy-in-canine-osteosarcoma-cell-lines
#5
M Massimini, C Palmieri, R De Maria, M Romanucci, D Malatesta, M De Martinis, L Maniscalco, A Ciccarelli, L Ginaldi, P Buracco, L Bongiovanni, L Della Salda
Canine osteosarcoma is highly resistant to current chemotherapy; thus, clarifying the mechanisms of tumor cell resistance to treatments is an urgent need. We tested the geldanamycin derivative 17-AAG (17-allylamino-17-demethoxygeldanamycin) prototype of Hsp90 (heat shock protein 90) inhibitors in 2 canine osteosarcoma cell lines, D22 and D17, derived from primary and metastatic tumors, respectively. With the aim to understand the interplay between cell death, autophagy, and mitophagy, in light of the dual effect of autophagy in regulating cancer cell viability and death, D22 and D17 cells were treated with different concentrations of 17-AAG (0...
May 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28402954/chaperone-mediated-autophagy-compensates-for-impaired-macroautophagy-in-the-cirrhotic-liver-to-promote-hepatocellular-carcinoma
#6
Srinivas Chava, Christine Lee, Yucel Aydin, Partha K Chandra, Asha Dash, Milad Chedid, Swan N Thung, Krzysztof Moroz, Tong Wu, Nabeen C Nayak, Srikanta Dash
Macroautophagy and chaperone-mediated autophagy (CMA) represent two major lysosomal degradation processes and often compensate for one another to facilitate cell survival. The aim of this study was to determine whether these autophagy pathways could compensate for one another to promote HCC cell survival in the cirrhotic liver. Analysis of normal liver tissue showed no expression of glypican-3 or p62 proteins, suggesting that macroautophagy is the major contributor to autophagic flux under non-pathological conditions...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28389753/the-role-of-hsp70-in-the-regulation-of-autophagy-in-gametogenesis-pregnancy-and-parturition
#7
Steven S Witkin, Tomi T Kanninen, Giovanni Sisti
Induction of the 70 kDa heat shock protein (hsp70) and autophagy are two major mechanisms that promote cell homeostasis during the rapid cell growth and differentiation characteristic of reproduction. Hsp70 insures proper assembly, conformation, and intracellular transport of nascent proteins. Autophagy removes from the cytoplasm proteins, other macromolecules, and organelles that are no longer functional or needed and recycles their components for synthesis of new products under nutritionally limiting conditions...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28360921/the-involvement-of-heat-shock-proteins-in-the-establishment-of-tomato-yellow-leaf-curl-virus-infection
#8
REVIEW
Rena Gorovits, Henryk Czosnek
Tomato yellow leaf curl virus (TYLCV), a begomovirus, induces protein aggregation in infected tomatoes and in its whitefly vector Bemisia tabaci. The interactions between TYLCV and HSP70 and HSP90 in plants and vectors are necessity for virus infection to proceed. In infected host cells, HSP70 and HSP90 are redistributed from a soluble to an aggregated state. These aggregates contain, together with viral DNA/proteins and virions, HSPs and components of the protein quality control system such as ubiquitin, 26S proteasome subunits, and the autophagy protein ATG8...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28337642/the-small-heat-shock-proteins-%C3%AE-b-crystallin-hspb5-and-hsp27-hspb1-inhibit-the-intracellular-aggregation-of-%C3%AE-synuclein
#9
Dezerae Cox, Heath Ecroyd
Protein homeostasis, or proteostasis, is the process of maintaining the conformational and functional integrity of the proteome. Proteostasis is preserved in the face of stress by a complex network of cellular machinery, including the small heat shock molecular chaperone proteins (sHsps), which act to inhibit the aggregation and deposition of misfolded protein intermediates. Despite this, the pathogenesis of several neurodegenerative diseases has been inextricably linked with the amyloid fibrillar aggregation and deposition of α-synuclein (α-syn)...
March 23, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28333578/hormetic-heat-shock-and-hsf-1-overexpression-improve-c-elegans-survival-and-proteostasis-by-inducing-autophagy
#10
Caroline Kumsta, Malene Hansen
The cellular recycling process of macroautophagy/autophagy is an essential homeostatic system induced by various stresses, but it remains unclear how autophagy contributes to organismal stress resistance. In a recent study, we report that a mild and physiologically beneficial ("hormetic") heat shock as well as overexpression of the heat-shock responsive transcription factor HSF-1 systemically increases autophagy in C. elegans. Accordingly, we found HSF-1- and heat stress-inducible autophagy to be required for C...
March 23, 2017: Autophagy
https://www.readbyqxmd.com/read/28301987/properties-of-epithelial-cells-and-vaginal-secretions-in-pregnant-women-when-lactobacillus-crispatus-or-lactobacillus-iners-dominate-the-vaginal-microbiome
#11
Julie Leizer, Dimitrios Nasioudis, Larry J Forney, G Maria Schneider, Karol Gliniewicz, Allison Boester, Steven S Witkin
OBJECTIVE: Our objective was to determine differences in properties of vaginal epithelial cells and the composition of vaginal secretions when Lactobacillus crispatus or Lactobacillus iners are numerically dominant in the vaginal microenvironment of pregnant women. METHODS: The vaginal microbiomes of 157 first-trimester pregnant women were identified by classifying partial 16S gene sequences amplified from the V1 to V3 region of bacterial ribosomal 16S RNA genes...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28293421/protein-misfolding-in-neurodegenerative-diseases-implications-and-strategies
#12
REVIEW
Patrick Sweeney, Hyunsun Park, Marc Baumann, John Dunlop, Judith Frydman, Ron Kopito, Alexander McCampbell, Gabrielle Leblanc, Anjli Venkateswaran, Antti Nurmi, Robert Hodgson
A hallmark of neurodegenerative proteinopathies is the formation of misfolded protein aggregates that cause cellular toxicity and contribute to cellular proteostatic collapse. Therapeutic options are currently being explored that target different steps in the production and processing of proteins implicated in neurodegenerative disease, including synthesis, chaperone-assisted folding and trafficking, and degradation via the proteasome and autophagy pathways. Other therapies, like mTOR inhibitors and activators of the heat shock response, can rebalance the entire proteostatic network...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28275944/fine-tuning-of-actin-dynamics-by-the-hspb8-bag3-chaperone-complex-facilitates-cytokinesis-and-contributes-to-its-impact-on-cell-division
#13
Alice Anaïs Varlet, Margit Fuchs, Carole Luthold, Herman Lambert, Jacques Landry, Josée N Lavoie
The small heat shock protein HSPB8 and its co-chaperone BAG3 are proposed to regulate cytoskeletal proteostasis in response to mechanical signaling in muscle cells. Here, we show that in dividing cells, the HSPB8-BAG3 complex is instrumental to the accurate disassembly of the actin-based contractile ring during cytokinesis, a process required to allow abscission of daughter cells. Silencing of HSPB8 markedly decreased the mitotic levels of BAG3 in HeLa cells, supporting its crucial role in BAG3 mitotic functions...
March 8, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28206988/inhibition-of-autophagy-blocks-cathepsins-tbid-mitochondrial-apoptotic-signaling-pathway-via-stabilization-of-lysosomal-membrane-in-ischemic-astrocytes
#14
Xian-Yong Zhou, Yu Luo, Yong-Ming Zhu, Zhi-He Liu, Thomas A Kent, Jia-Guo Rong, Wei Li, Shi-Gang Qiao, Min Li, Yong Ni, Kazumi Ishidoh, Hui-Ling Zhang
Our previous study and others have demonstrated that autophagy is activated in ischemic astrocytes and contributes to astrocytic cell death. However, the mechanisms of ischemia-induced autophagy remain largely unknown. In this study, we established a rat's model of permanent middle cerebral artery occlusion (pMCAO) and an in vitro oxygen and glucose deprivation (OGD) model. Autophagy was inhibited by either pharmacological treatment with 3-methyladenine (3-MA) and wortmannin (Wort) or genetic treatment with knockdown of Atg5 in primary cultured astrocytes and knockout of Atg5 in mouse embryonic fibroblast (MEF) cells, respectively...
February 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28188022/interplay-between-hsp90-and-nrf2-pathways-in-diabetes-associated-atherosclerosis
#15
Iolanda Lazaro, Ainhoa Oguiza, Carlota Recio, Laura Lopez-Sanz, Susana Bernal, Jesus Egido, Carmen Gomez-Guerrero
INTRODUCTION: Oxidative stress and inflammation are determinant processes in the development of diabetic vascular complications. Heat shock protein 90 (HSP90) overexpression in atherosclerotic plaques plays a role in sustaining inflammatory mechanisms, and its specific inhibition prevents atherosclerosis. The present work investigates, in a mouse model of diabetes-driven atherosclerosis, whether atheroprotection by pharmacological HSP90 inhibition is accomplished by bolstering antioxidant defense mechanisms headed by nuclear factor erythroid-derived 2-like 2 (Nrf2)...
February 7, 2017: Clínica e Investigación en Arteriosclerosis
https://www.readbyqxmd.com/read/28157209/autophagy-induced-by-damps-facilitates-the-inflammation-response-in-lungs-undergoing-ischemia-reperfusion-injury-through-promoting-traf6-ubiquitination
#16
Xingguang Liu, Hao Cao, Jian Li, Bo Wang, Peng Zhang, Xu Dong Zhang, Zhongmin Liu, Hongbin Yuan, Zhenzhen Zhan
Lung ischemia-reperfusion (I/R) injury remains one of the most common complications after various cardiopulmonary surgeries. The inflammation response triggered by the released damage-associated molecular patterns (DAMPs) aggravates lung tissue damage. However, little is known about the role of autophagy in the pathogenesis of lung I/R injury. Here, we report that a variety of inflammation-related and autophagy-associated genes are rapidly upregulated, which facilitate the inflammation response in a minipig lung I/R injury model...
April 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28131906/a-novel-hdac6-inhibitor-tubastatin-a-controls-hdac6-p97-vcp-mediated-ubiquitination-autophagy-turnover-and-reverses-temozolomide-induced-er-stress-tolerance-in-gbm-cells
#17
Zong-Yang Li, Ce Zhang, Yuan Zhang, Lei Chen, Bao-Dong Chen, Qing-Zhong Li, Xie-Jun Zhang, Wei-Ping Li
Temozolomide (TMZ) is the cornerstone of therapy for glioblastoma multiforme (GBM). However, its efficacy is limited due to the development of multidrug resistance (MDR). In this study, we first identified the occurrence of ER stress-tolerance (ERST) in glioma cells and confirmed that ERST was positively correlated with TMZ resistance. We further showed that the seesaw-effect of HDAC6-p97/VCP (increased HDAC6 and decreased p97/VCP) in glioma cells was crucial to ERST-associated TMZ resistance. Moreover, the combination treatment of Tubastatin A (TUB, a selective inhibitor of HDAC6) and TMZ synergistically overcame ERST, reduced cell viability and induced apoptosis in TMZ-resistant glioma cells...
April 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28120291/role-of-shsps-in-organizing-cytosolic-protein-aggregation-and-disaggregation
#18
REVIEW
Axel Mogk, Bernd Bukau
Small heat shock proteins (sHsps) exhibit an ATP-independent chaperone activity to prevent the aggregation of misfolded proteins in vitro. The seemingly conflicting presence of sHsps in insoluble protein aggregates in cells obstructs a precise definition of sHsp function in proteostasis networks. Recent findings specify sHsp activities in protein quality control systems. The sHsps of yeast, Hsp42 and Hsp26, interact with early unfolding intermediates of substrates, keeping them in a ready-to-refold conformation close to the native state...
January 24, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28116619/hdac6-regulates-sensitivity-to-cell-death-in-response-to-stress-and-post-stress-recovery
#19
Hyun-Wook Ryu, Hye-Rim Won, Dong Hoon Lee, So Hee Kwon
Histone deacetylase 6 (HDAC6) plays an important role in stress responses such as misfolded protein-induced aggresomes, autophagy, and stress granules. However, precisely how HDAC6 manages response during and after cellular stress remains largely unknown. This study aimed to investigate the effect of HDAC6 on various stress and post-stress recovery responses. We showed that HIF-1α protein levels were reduced in HDAC6 knockout (KO) MEFs compared to wild-type (WT) MEFs in hypoxia. Furthermore, under hypoxia, HIF-1α levels were also reduced following rescue with either a catalytically inactive or a ubiqiutin-binding mutant HDAC6...
March 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28110670/galnt6-stabilizes-grp78-protein-by-o-glycosylation-and-enhances-its-activity-to-suppress-apoptosis-under-stress-condition
#20
Jiaying Lin, Suyoun Chung, Koji Ueda, Koichi Matsuda, Yusuke Nakamura, Jae-Hyun Park
We previously reported that overexpression of an O-type glycosyltransferase, GALNT6 (polypeptide N-acetylgalactosaminyltransferase 6) played critical roles in mammary carcinogenesis. To further investigate the biological function of GALNT6, we screened a substrate protein(s) of GALNT6 using a VVA (Vicia villosa agglutinin) lectin (specific to GalNAc-Ser/Thr) pull-down method followed by mass spectrometry analysis. Here we report GRP78 (glucose-regulated protein 78, also known as HSPA5, heat shock 70 kDa protein 5), which is highly expressed in cancer cells and indicated to play important roles in various cellular processes including ER (endoplasmic reticulum) stress and autophagy, as a novel substrate of GALNT6...
January 2017: Neoplasia: An International Journal for Oncology Research
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