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HSP27 extracellular

Priscilla Segges, Stephany Corrêa, Bárbara Du Rocher, Gabriela Vera-Lozada, Flavia Krsticevic, Debora Arce, Cinthya Sternberg, Eliana Abdelhay, Rocio Hassan
Classical Hodgkin lymphoma (cHL) cells overexpress heat-shock protein 90 (HSP90), an important intracellular signaling hub regulating cell survival, which is emerging as a promising therapeutic target. Here, we report the antitumor effect of celastrol, an anti-inflammatory compound and a recognized HSP90 inhibitor, in Hodgkin and Reed-Sternberg cell lines. Two disparate responses were recorded. In KM-H2 cells, celastrol inhibited cell proliferation, induced G0/G1 arrest, and triggered apoptosis through the activation of caspase-3/7...
March 13, 2018: International Journal of Molecular Sciences
Joanna Homa
Invertebrate immunity is associated with natural mechanisms that include cellular and humoral elements, similar to those that play a role in vertebrate innate immune responses. Formation of extracellular traps (ETs) is a newly discovered mechanism to combat pathogens, operating not only in vertebrate leucocytes but also in invertebrate immune cells. The ET components include extracellular DNA (exDNA), antimicrobial proteins and histones. Formation of mammalian ETs depends on enzymes such as neutrophil elastase, myeloperoxidase, the citrullination of histones and protease activity...
February 5, 2018: Cell and Tissue Research
Dezerae Cox, Daniel R Whiten, James Brown, Mathew H Horrocks, Rebecca San Gil, Christopher M Dobson, David Klenerman, Antoine M van Oijen, Heath Ecroyd
Proteostasis, or protein homeostasis, encompasses the maintenance of the conformational and functional integrity of the proteome and involves an integrated network of cellular pathways. Molecular chaperones, such as the small heat shock proteins (sHsps), are a key element of the proteostasis network that have crucial roles in inhibiting the aggregation of misfolded proteins. Failure of the proteostasis network can lead to the accumulation of misfolded proteins into intra- and extracellular deposits. Deposits containing fibrillar forms of α- synuclein (α-syn) are characteristic of neurodegenerative disorders including Parkinson's disease and dementia with Lewy bodies...
January 30, 2018: Journal of Biological Chemistry
Guopei Zheng, Zhijie Zhang, Hao Liu, Yan Xiong, Liyun Luo, Xiaoting Jia, Cong Peng, Qiong Zhang, Nan Li, Yixue Gu, Minying Lu, Ying Song, Hao Pan, Jinbao Liu, Wanqing Liu, Zhimin He
PURPOSE: Squamous cell carcinoma of tongue (SCCT) is the most common type of the oral cavity carcinoma. Chemo-resistance in SCCT is common and the underlying mechanism remains largely unknown. We aim to identify key molecules and signaling pathways mediating chemo-resistance in SCCT. EXPERIMENTAL DESIGN: Using a proteomic approach we identify that the HSP27 was a potential mediator for chemo-resistance in SCCT cells. To further validate this role of HSP27, we performed various mechanistic studies using in vitro and in vivo models as well as serum and tissue samples of SCCT patients...
December 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Alice A Han, Holly N Currie, Matthew S Loos, Giovanni Scardoni, Julie V Miller, Nicole Prince, Julia A Mouch, Jonathan W Boyd
Investigations of cellular responses involved in injury and repair processes have generated valuable information contributing to the advancement of wound healing and treatments. Intra- and extracellular regulators of healing mechanisms, such as cytokines, signaling proteins, and growth factors, have been described to possess significant roles in facilitating optimal recovery. This study explored a collection of 30 spatiotemporal responses comprised of cytokines (IL-1α, IL-1ß, IL-2, IL-6, TNF-α, MIP-1α), intracellular proteins (Akt, c-Jun, CREB, ERK1/2, JNK, MEK1, p38, p53, p90RSK), phosphorylated proteins (p-Akt, p-c-Jun, p-CREB, p-ERK1/2, p-GSK-3α/ß, p-HSP27, p-IκBα, p-JNK, p-MEK1, p-p38, p-p70S6K, p-p90RSK, p-STAT2, p-STAT3), and a protease (Caspase-3), measured in skeletal muscle tissue following a traumatic injury (rodent Gustilo IIIB fracture)...
November 2, 2017: Cytokine
Makiko Tsuboi, Keisuke Taniuchi, Takahiro Shimizu, Motoaki Saito, Toshiji Saibara
HOX genes encode transcription factors that function as sequence-specific transcription factors that are involved in cellular proliferation, differentiation, and death. The aim of this study was to investigate the role of a HOX family protein, HOXB7, in the motility and invasiveness of pancreatic cancer cells. We previously identified a HOXB7 transcript that is one of a number of transcripts that are preferentially translated in membrane protrusions in pancreatic cancer cells. Immunocytochemistry showed that HOXB7 was localized to the cell protrusions of migrating pancreatic cancer cells...
October 27, 2017: Journal of Biological Chemistry
Stéphanie Simoncini, Anne-Line Chateau, Stéphane Robert, Dilyana Todorova, Catherine Yzydorzick, Romaric Lacroix, Isabelle Ligi, Laurence Louis, Richard Bachelier, Umberto Simeoni, Frédérique Magdinier, Françoise Dignat-George, Florence Sabatier
Senescent cells may exert detrimental effect on microenvironment through the secretion of soluble factors and the release of extracellular vesicles, such as microparticles, key actors in ageing and cardiovascular diseases. We previously reported that sirtuin-1 (SIRT1) deficiency drives accelerated senescence and dysfunction of endothelial colony-forming cells (ECFC) in PT neonates. Because preterm birth (PT) increases the risk for cardiovascular diseases during neonatal period as well as at adulthood, we hypothesized that SIRT1 deficiency could control the biogenesis of microparticles as part of a senescence-associated secretory phenotype (SASP) of PT-ECFC and investigated the related molecular mechanisms...
August 15, 2017: Scientific Reports
Takashi Onuma, Kumiko Tanabe, Yuko Kito, Masanori Tsujimoto, Kodai Uematsu, Yukiko Enomoto, Rie Matsushima-Nishiwaki, Tomoaki Doi, Kiyoshi Nagase, Shigeru Akamatsu, Haruhiko Tokuda, Shinji Ogura, Toru Iwama, Osamu Kozawa, Hiroki Iida
Sphingosine 1-phosphate (S1P) is as an extracellular factor that acts as a potent lipid mediator by binding to specific receptors, S1P receptors (S1PRs). However, the precise role of S1P in human platelets that express S1PRs has not yet been fully clarified. We previously reported that heat shock protein 27 (HSP27) is released from human platelets accompanied by its phosphorylation stimulated by collagen. In the present study, we investigated the effect of S1P on the collagen-induced platelet activation. S1P pretreatment markedly attenuated the collagen-induced aggregation...
August 2017: Thrombosis Research
Yihua Bei, Tianzhao Xu, Dongchao Lv, Pujiao Yu, Jiahong Xu, Lin Che, Avash Das, John Tigges, Vassilios Toxavidis, Ionita Ghiran, Ravi Shah, Yongqin Li, Yuhui Zhang, Saumya Das, Junjie Xiao
Extracellular vesicles (EVs) serve an important function as mediators of intercellular communication. Exercise is protective for the heart, although the signaling mechanisms that mediate this cardioprotection have not been fully elucidated. Here using nano-flow cytometry, we found a rapid increase in plasma EVs in human subjects undergoing exercise stress testing. We subsequently identified that serum EVs were increased by ~1.85-fold in mice after 3-week swimming. Intramyocardial injection of equivalent quantities of EVs from exercised mice and non-exercised controls provided similar protective effects against acute ischemia/reperfusion (I/R) injury in mice...
July 2017: Basic Research in Cardiology
Daiana G Alvarez-Olmedo, Veronica S Biaggio, Geremy A Koumbadinga, Nidia N Gómez, Chunhua Shi, Daniel R Ciocca, Zarah Batulan, Mariel A Fanelli, Edward R O'Brien
Cadmium (Cd) is a carcinogen with several well-described toxicological effects in humans, but its molecular mechanisms are still not fully understood. Overexpression of heat shock protein 27 (HSP27/HSPB1)-a multifunctional protein chaperone-has been shown to protect cells from oxidative damage and apoptosis triggered by Cd exposure. The aims of this work were to investigate the potential use of extracellular recombinant HSP27 to prevent/counteract Cd-induced cellular toxicity and to evaluate if peroxynitrite was involved in the development of Cd-induced toxicity...
May 2017: Cell Stress & Chaperones
María M Leal-Lasarte, Jaime M Franco, Adahir Labrador-Garrido, David Pozo, Cintia Roodveldt
Dysregulated microglial responses are central in neurodegenerative proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar disease (FTLD). Pathologic TDP-43, which is typically found in intracellular inclusions, is a misfolding protein with emerging roles in ALS and FTLD. Recently, TDP-43 species have been found in extracellular fluids of patients; however, the overall implications of TDP-43-mediated signaling linked to neuroinflammation are poorly understood. Our work-the first, to our knowledge, to focus on innate immunity responses to TDP-43 aggregates-shows that such species are internalized by microglia and cause abnormal mobilization of endogenous TDP-43...
July 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Matthias B Stope, Gerd Klinkmann, Karoline Diesing, Dominique Koensgen, Martin Burchardt, Alexander Mustea
The heat shock protein HSP27 has been correlated in ovarian cancer (OC) patients with aggressiveness and chemoresistance and, therefore, represents a promising potential biomarker for OC diagnosis, prognosis, and treatment response. Notably, secretion of soluble HSP27 has been described by a few cell types and may take place as well in OC cells. Therefore, we studied HSP27 secretion mechanisms under diverse cellular conditions in an OC cell model system. Secretion of HSP27 was characterized after overexpression of HSP27 by transfected plasmids and after heat shock...
2017: Disease Markers
Lorena De Mena, Deepak Chhangani, Pedro Fernandez-Funez, Diego E Rincon-Limas
Self-association of amyloidogenic proteins is the main pathological trigger in a wide variety of neurodegenerative disorders. These aggregates are deposited inside or outside the cell due to hereditary mutations, environmental exposures or even normal aging. Cumulative evidence indicates that the heat shock chaperone Hsp70 possesses robust neuroprotection against various intracellular amyloids in Drosophila and mouse models. However, its protective role against extracellular amyloids was largely unknown as its presence outside the cells is very limited...
July 3, 2017: Fly
Lihua Ao, Yufeng Zhai, Chunhua Jin, Joseph C Cleveland, David A Fullerton, Xianzhong Meng
BACKGROUND: While cardiac functional recovery is attenuated in the elderly following cardiac surgery with obligatory global myocardial ischemia/reperfusion (I/R), the underlying mechanism remains incompletely understood. We observed previously that human and mouse myocardium releases heat shock protein (HSP) 27 during global I/R. Extracellular HSP27 induces myocardial inflammatory response and plays a role in post-ischemic cardiac dysfunction in adult mouse hearts. OBJECTIVE: This study was to determine the role of extracellular HSP27 and Toll-like receptor 4 (TLR4) in the attenuated functional recovery in aging mouse hearts following global I/R...
December 19, 2016: Molecular Medicine
Ilona Hromadnikova, Lenka Dvorakova, Katerina Kotlabova, Andrea Kestlerova, Lucie Hympanova, Veronika Novotna, Jindrich Doucha, Ladislav Krofta
BACKGROUND & OBJECTIVES: Heat shock proteins (Hsp) are ubiquitously distributed phylogenetically conserved molecules that regulate cellular homeostasis and maintain the integrity and function of cellular proteins. Increased levels of Hsp in maternal circulation have been shown to be associated with increased risk of pregnancy related complications. The objective of this study was to explore extracellular Hsp mRNA levels in maternal circulation and quantified Hsp27, Hsp60, Hsp70, Hsp90 and Hsp70 binding protein 1 (HspBP1) mRNAs in maternal plasma samples using real-time reverse-transcriptase polymerase chain reaction...
August 2016: Indian Journal of Medical Research
J Zhang, K B Storey
Larvae of the goldenrod gall moth, Epiblema scudderiana, use the freeze avoidance strategy of cold hardiness to survive the winter. Here we report that protein kinase-dependent signal transduction featuring mitogen-activated protein kinase (MAPK) signalling cascades (extracellular signal regulated kinase, c-jun N-terminal kinase and p38 MAPK pathways) and the Akt (also known as protein kinase B, or PKB) pathway could be integral parts of the development of cold hardiness by E. scudderiana. We used Luminex technology to assess the protein levels and phosphorylation status of key components and downstream targets of those pathways in larvae in response to low temperature acclimation...
November 23, 2016: Insect Molecular Biology
Xiaodong Chen, Radouil Tzekov, Mingyang Su, Haiyan Hong, Wang Min, Aidong Han, Wensheng Li
Abnormal survival of retinal pigment epithelium (RPE) cells contributes to the pathogenesis of proliferative vitreoretinopathy (PVR), a sight-threatening disease. In this study, we explored the effect of the anti-rheumatic agent auranofin (AF) on RPE cell survival and studied the underlying signaling mechanisms in vitro. Our results showed that AF inhibited ARPE-19 cell survival in a dose and time-dependent manner. Application of AF induced several effects: a significant decrease in total epidermal growth factor receptor (EGFR) and an increase in phosphorylated EGFR and mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), P38 mitogen-activated protein kinase (P38MAPK), c-Jun N-terminal kinase (JNK), c-Jun, mitogen activated protein kinase activated protein kinase 2(MAPKAPK2), and heat shock protein 27 (HSP27)...
2016: PloS One
Kirsten F Smit, Daniel Brevoord, Stefan De Hert, Bas A de Mol, Raphaela P Kerindongo, Susan van Dieren, Wolfgang S Schlack, Markus W Hollmann, Nina C Weber, Benedikt Preckel
BACKGROUND: The noble gas helium induces pre- and postconditioning in animals and humans. Volatile anesthetics induce cardioprotection in humans undergoing coronary artery bypass graft (CABG) surgery. We hypothesized that helium induces pre- and postconditioning in CABG-patients, affecting signaling molecules protein kinase C-epsilon (PKC-ε), p38 mitogen activated protein kinase (p38 MAPK), extracellular signal-regulated kinase 1/2 (ERK-1/2) and heat shock protein 27 (HSP-27) within cardiac tissue, and reducing postoperative troponin levels...
October 14, 2016: Journal of Translational Medicine
Gwangchul Lee, Bora Kim, Youngjong Ko, Mineon Park, Donghwi Kim, Kang Hyeon Ryu, Yong Cheol Jun, Hong Moon Sohn, Wonbong Lim
OBJECTIVE: This study was designed to investigate the effect of 635-nm irradiation from a light-emitting diode (LED) on osteoclastogenesis in receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL)-stimulated mouse bone marrow-derived macrophages (BMMs). We determined whether 635-nm irradiation modulated the RANKL-induced osteoclastic signaling pathway in heat shock protein-27 (HSP27)-silenced cells and analyzed the functional cross talk between these factors in osteoclastic differentiation and activation...
February 2017: Photomedicine and Laser Surgery
Zarah Batulan, Vivek Krishna Pulakazhi Venu, Yumei Li, Geremy Koumbadinga, Daiana Gisela Alvarez-Olmedo, Chunhua Shi, Edward R O'Brien
Heat shock protein 27 (HSP27) is traditionally viewed as an intracellular chaperone protein with anti-apoptotic properties. However, recent data indicate that a number of heat shock proteins, including HSP27, are also found in the extracellular space where they may signal via membrane receptors to alter gene transcription and cellular function. Therefore, there is increasing interest in better understanding how HSP27 is released from cells, its levels and composition in the extracellular space, and the cognate cell membrane receptors involved in effecting cell signaling...
2016: Frontiers in Immunology
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