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autophagy and heat shock protein

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https://www.readbyqxmd.com/read/28627586/hsp70-acetylation-prevents-caspase-dependent-independent-apoptosis-and-autophagic-cell-death-in-cancer-cells
#1
Yoo Hoi Park, Ji Hae Seo, Ji-Hyeon Park, Hye Shin Lee, Kyu-Won Kim
Cancer cells are continuously challenged by adverse environmental factors including hypoxia, metabolite restriction, and immune reactions, and must adopt diverse strategies to survive. Heat shock protein (Hsp) 70 plays a central role in protection against stress-induced cell death by maintaining protein homeostasis and interfering with the process of programmed cell death. Recent findings have suggested that Hsp70 acetylation is a key regulatory modification required for its chaperone activity, but its relevance in the process of programmed cell death and the underlying mechanisms involved are not well understood...
June 12, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28624441/hsp90-inhibitor-geldanamycin-attenuates-the-cytotoxicity-of-sunitinib-in-cardiomyocytes-via-inhibition-of-the-autophagy-pathway
#2
Takayuki Kimura, Mai Uesugi, Kazuma Takase, Norimasa Miyamoto, Kohei Sawada
Sunitinib malate (sunitinib) is an orally available, multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activities. Although sunitinib is effective for the treatment of patients with gastrointestinal stromal tumor, advanced renal cell carcinoma, or pancreatic neuroendocrine tumor, adverse cardiac events associated with sunitinib administration have been reported. Here, we examined the effect of geldanamycin, an inhibitor of heat shock protein (Hsp) 90, on sunitinib-induced cytotoxicity in cardiomyocytes...
June 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28608264/the-small-heat-shock-protein-b8-hspb8-efficiently-removes-aggregating-species-of-dipeptides-produced-in-c9orf72-related-neurodegenerative-diseases
#3
Riccardo Cristofani, Valeria Crippa, Giulia Vezzoli, Paola Rusmini, Mariarita Galbiati, Maria Elena Cicardi, Marco Meroni, Veronica Ferrari, Barbara Tedesco, Margherita Piccolella, Elio Messi, Serena Carra, Angelo Poletti
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two neurodegenerative diseases in which similar pathogenic mechanisms are involved. Both diseases associate to the high propensity of specific misfolded proteins, like TDP-43 or FUS, to mislocalize and aggregate. This is partly due to their intrinsic biophysical properties and partly as a consequence of failure of the neuronal protein quality control (PQC) system. Several familial ALS/FTD cases are linked to an expansion of a repeated G4C2 hexanucleotide sequence present in the C9ORF72 gene...
June 12, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28559049/attenuation-of-thioacetamide-induced-hepatocellular-injury-by-short-term-repeated-injections-associated-with-down-regulation-of-metabolic-enzymes-and-relationship-with-mhc-class-ii-presenting-cells
#4
Mizuki Kuramochi, Takeshi Izawa, Munmun Pervin, Alexandra Bondoc, Mitsuru Kuwamura, Jonathan LaMarre, Jyoji Yamate
The liver is the primary organ participating in the metabolism of xenobiotics and is therefore an important target in the safety assessment of drugs, chemicals and environmental toxins. Drug-induced liver injury (DILI) has recently become widely recognized in human medicine as an adverse event. The progression of DILI often involves "damage-associated molecular patterns" (DAMPs) of gene and protein expression such as high-mobility group boxes (HMGBs), S100 proteins and heat shock proteins (Hsp). DAMPs are released from injured or necrotic cells and are bound to Toll-like receptors (TLRs) and modulate inflammatory reactions...
May 27, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28542269/the-small-molecule-kinase-inhibitor-d11-counteracts-17-aag-mediated-up-regulation-of-hsp70-in-brain-cancer-cells
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28389753/the-role-of-hsp70-in-the-regulation-of-autophagy-in-gametogenesis-pregnancy-and-parturition
#11
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
#12
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
#13
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)...
July 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
#14
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
#15
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
#16
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
#17
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...
July 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
#18
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
#19
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
#20
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
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