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https://www.readbyqxmd.com/read/27906059/a-mitochondrial-hsp70-hspa9b-is-linked-to-miltefosine-resistance-and-stress-response-in-leishmania-donovani
#1
P Vacchina, B Norris-Mullins, E S Carlson, M A Morales
BACKGROUND: Protozoan parasites of the genus Leishmania are responsible for leishmaniasis, a neglected tropical disease affecting millions worldwide. Visceral leishmaniasis (VL), caused by Leishmania donovani, is the most severe form of leishmaniasis with high rates of mortality if left untreated. Current treatments include pentavalent antimonials and amphotericin B. However, high toxicity and emergence of resistance hinder the success of these options. Miltefosine (HePC) is the first oral treatment available for leishmaniasis...
December 1, 2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27903966/pde5-inhibitors-enhance-the-lethality-of-pemetrexed-through-inhibition-of-multiple-chaperone-proteins-and-via-the-actions-of-cyclic-gmp-and-nitric-oxide
#2
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Sarah Gordon, Paul Dent
Phosphodiesterase 5 (PDE5) inhibitors prevent the breakdown of cGMP that results in prolonged protein kinase G activation and the generation of nitric oxide. PDE5 inhibitors enhanced the anti-NSCLC cell effects of the NSCLC therapeutic pemetrexed. [Pemetrexed + sildenafil] activated an eIF2α - ATF4 - CHOP - Beclin1 pathway causing formation of toxic autophagosomes; activated a protective IRE1 - XBP-1 - chaperone induction pathway; and activated a toxic eIF2α - CHOP - DR4 / DR5 / CD95 induction pathway. [Pemetrexed + sildenafil] reduced the expression of c-FLIP-s, MCL-1 and BCL-XL that was blocked in a cell-type -dependent fashion by either over-expression of HSP90 / GRP78 / HSP70 / HSP27 or by blockade of eIF2α-CHOP signaling...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901028/small-heat-shock-proteins-sequester-misfolding-proteins-in-near-native-conformation-for-cellular-protection-and-efficient-refolding
#3
Sophia Ungelenk, Fatemeh Moayed, Chi-Ting Ho, Tomas Grousl, Annette Scharf, Alireza Mashaghi, Sander Tans, Matthias P Mayer, Axel Mogk, Bernd Bukau
Small heat shock proteins (sHsp) constitute an evolutionary conserved yet diverse family of chaperones acting as first line of defence against proteotoxic stress. sHsps coaggregate with misfolded proteins but the molecular basis and functional implications of these interactions, as well as potential sHsp specific differences, are poorly explored. In a comparative analysis of the two yeast sHsps, Hsp26 and Hsp42, we show in vitro that model substrates retain near-native state and are kept physically separated when complexed with either sHsp, while being completely unfolded when aggregated without sHsps...
November 30, 2016: Nature Communications
https://www.readbyqxmd.com/read/27900018/influence-of-ezrin-shrna-in-combination-with-hsp70-on-the-apoptosis-and-proliferation-of-osteosarcoma-cells
#4
Qin Yao, Yihua Pei, Huiqin Zhuo, Bozhen Xie
Ezrin and heat shock protein (HSP)70 have been reported to regulate cell apoptosis and tumor development of osteosarcoma. However, there has not been reported the synergy effect of knocking down ezrin and overexpressing HSP70. In the present study, two vectors, pGFP-V-RS-shRNA and pGFP-V-RS-shRNA-HSP70, were constructed and transfected into LM8 cells [denoted as small hairpin (sh)RNA group and dual group, respectively]. The apoptosis rates in these two transfected groups were significantly higher than those in the control group (empty vector) (P=0...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27896629/remote-limb-ischemic-preconditioning-protects-rats-against-cerebral-ischemia-via-hif-1%C3%AE-ampk-hsp70-pathway
#5
Ming Xia, Qian Ding, Zhidan Zhang, Qinggen Feng
Remote limb ischemic preconditioning (RIPC) is a clinically feasible strategy to protect against ischemia/reperfusion injury, but the knowledge concerning the mechanism underlying RIPC is scarce. This study was performed to examine the effect of RIPC on brain tissue suffering from ischemia challenge and explore its underlying mechanism in a rat model. The animals were divided into four groups: Sham, middle cerebral artery occlusion (MCAO), RIPC, and MCAO+RIPC. We found that previous exposure to RIPC significantly attenuated neurological dysfunction and lessened brain edema in MCAO+RIPC group...
November 28, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27894882/comparing-biomarker-responses-during-thermal-acclimation-a-lethal-vs-non-lethal-approach-in-a-tropical-reef-clownfish
#6
Carolina Madeira, Diana Madeira, Mário S Diniz, Henrique N Cabral, Catarina Vinagre
Knowledge of thermal stress biology for most tropical fish species in reef ecosystems under climate change is still quite limited. Thus, the objective of this study was to measure the time-course changes of thermal stress biomarkers in the commercially exploited coral reef fish Amphiprion ocellaris, during a laboratory simulated event of increased temperature. Heat shock protein 70kDa (Hsp70) and total ubiquitin (Ub) were determined in the muscle (lethal method) and in the fin (non-lethal alternative method) under two temperature treatments (control - 26°C and elevated temperature - 30°C) throughout one month with weekly samplings...
November 25, 2016: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/27893783/role-of-pten-in-oxidative-stress-and-dna-damage-in-the-liver-of-whole-body-pten-haplodeficient-mice
#7
Ezgi Eyluel Bankoglu, Oliver Tschopp, Johannes Schmitt, Philipp Burkard, Daniel Jahn, Andreas Geier, Helga Stopper
Type 2 diabetes (T2DM) and obesity are frequently associated with non-alcoholic fatty liver disease (NAFLD) and with an elevated cancer incidence. The molecular mechanisms of carcinogenesis in this context are only partially understood. High blood insulin levels are typical in early T2DM and excessive insulin can cause elevated reactive oxygen species (ROS) production and genomic instability. ROS are important for various cellular functions in signaling and host defense. However, elevated ROS formation is thought to be involved in cancer induction...
2016: PloS One
https://www.readbyqxmd.com/read/27891174/combination-of-cisplatin-and-bromelain-exerts-synergistic-cytotoxic-effects-against-breast-cancer-cell-line-mda-mb-231-in-vitro
#8
Ahmad Zaim Mat Pauzi, Swee Keong Yeap, Nadiah Abu, Kian Lam Lim, Abdul Rahman Omar, Suraini Abdul Aziz, Adam Leow Thean Chow, Tamilselvan Subramani, Soon Guan Tan, Noorjahan Banu Alitheen
BACKGROUND: Bromelain, which is a cysteine endopeptidase commonly found in pineapple stems, has been investigated as a potential anti-cancer agent for the treatment of breast cancer. However, information pertaining to the effects of combining bromelain with existing chemotherapeutic drugs remains scarce. This study aimed to investigate the possible synergistic cytotoxic effects of using bromelain in combination with cisplatin on MDA-MB-231 human breast cancer cells. METHOD: MDA-MB-231 cells were treated with different concentrations (0...
2016: Chinese Medicine
https://www.readbyqxmd.com/read/27890585/cadmium-in%C3%A2-vivo-exposure-alters-stress-response-and-endocrine-related-genes-in-the-freshwater-snail-physa-acuta-new-biomarker-genes-in-a-new-model-organism
#9
Pedro Martínez-Paz, Mónica Morales, Paloma Sánchez-Argüello, Gloria Morcillo, José Luis Martínez-Guitarte
The freshwater snail Physa acuta is a sensitive organism to xenobiotics that is appropriate for toxicity testing. Cadmium (Cd) is a heavy metal with known toxic effects on several organisms, which include endocrine disruption and activation of the cellular stress responses. There is scarce genomic information on P. acuta; hence, in this work, we identify several genes related to the hormonal system, the stress response and the detoxification system to evaluate the effects of Cd. The transcriptional activity of the endocrine-related genes oestrogen receptor (ER), oestrogen-related receptor (ERR), and retinoid X receptor (RXR), the heat shock proteins genes hsp70 and hsp90 and a metallothionein (MT) gene was analysed in P...
November 24, 2016: Environmental Pollution
https://www.readbyqxmd.com/read/27890044/effect-of-dietary-manganese-on-antioxidant-status-and-expressions-of-heat-shock-proteins-and-factors-in-tissues-of-laying-broiler-breeders-under-normal-and-high-environmental-temperatures
#10
Yong-Wen Zhu, Lin Lu, Wen-Xiang Li, Li-Yang Zhang, Cheng Ji, Xi Lin, Hsiao-Ching Liu, Jack Odle, Xu-Gang Luo
To investigate the effect of Mn on antioxidant status and on the expressions of heat shock proteins/factors in tissues of laying broiler breeders subjected to heat challenge, we used a completely randomised design (n 6) with a factorial arrangement of 2 environmental temperatures (normal, 21±1°C, and high, 32±1°C)×3 dietary Mn treatments (a Mn-unsupplemented basal diet (CON), or a basal diet supplemented with 120 mg Mn/kg diet, either as inorganic Mn sulphate (iMn) or as organic Mn proteinate (oMn)). There were no interactions (P>0·10) between environmental temperature and dietary Mn in any of the measured indices...
November 28, 2016: British Journal of Nutrition
https://www.readbyqxmd.com/read/27889508/physiological-responses-and-changes-in-gene-expression-in-the-large-yellow-croaker-larimichthys-crocea-following-exposure-to-hypoxia
#11
Qian-Feng Wang, Wei-Liang Shen, Cong-Cong Hou, Cheng Liu, Xiong-Fei Wu, Jun-Quan Zhu
Organisms at all levels of evolutionary complexity react to hypoxic stress. To clarify the effects of acute hypoxia on physiological and biochemical responses of Larimichthys crocea, we measured the activity levels of the antioxidant enzymes superoxide dismutase and catalase, hemoglobin concentration, functional indices of the liver (aspartate transaminase, alanine transaminase), heart (phosphocreatine kinase), and immune system (alkaline phosphatase), as well as mRNA expression levels of the immunity-related genes Hsp70 and HIF-1α at different time points of hypoxic...
November 24, 2016: Chemosphere
https://www.readbyqxmd.com/read/27888131/hsp70-and-hsp90-are-involved-in-shrimp-penaeus-vannamei-tolerance-to-ahpnd-causing-strain-of-vibrio-parahaemolyticus-after-non-lethal-heat-shock
#12
Wisarut Junprung, Premruethai Supungul, Anchalee Tassanakajon
Acute hepatopancreatic necrosis disease (AHPND) caused by Vibrio parahaemolyticus carrying toxin-producing plasmid, has led to severe mortalities in farmed penaeid shrimp throughout Asia. Previous studies reported that a non-lethal heat shock (NLHS) could enhance disease tolerance in aquatic animals. Here, we investigate whether the NLHS could enhance the survival of shrimp Peneaus vannamei upon challenge with an AHPND-causing strain of V. Parahaemolyticus (VPAHPND). Two NLHS conditions, acute and chronic NLHSs, were used...
November 22, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27887849/inhibition-of-heat-shock-protein-hsp-90-potentiates-the-antiproliferative-and-pro-apoptotic-effects-of-2-4-fluoro-phenylamino-4h-1-3-thiazine-6-5-b-indole-in-a2780cis-cells
#13
Zuzana Solárová, Martin Kello, Lenka Varinská, Mariana Budovská, Peter Solár
Ovarian carcinoma is initially sensitive to platinum-based therapy, but become resistant over time. The study of cancer sensitizing substance is therefore the major challenge for a number of scientific groups. Our experiments were carried out on human ovarian adenocarcinoma A2780cis cells resistant to cisplatin and their response to 2-(4'fluoro-phenylamino)-4H-1,3-thiazine[6,5-b]indole (thiazine[6,5-b]indole) and/or heat shock protein (Hsp) 90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) using proliferation assay, cell cycle analysis and monitoring of apoptosis were examined...
November 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27887635/anisakis-pegreffii-nematoda-anisakidae-products-modulate-oxidative-stress-and-apoptosis-related-biomarkers-in-human-cell-lines
#14
Concetta Maria Messina, Federica Pizzo, Andrea Santulli, Ivana Bušelić, Mate Boban, Stjepan Orhanović, Ivona Mladineo
BACKGROUND: In countries with elevated prevalence of zoonotic anisakiasis and high awareness of this parasitosis, a considerable number of cases that associate Anisakis sp. (Nematoda, Anisakidae) and different bowel carcinomas have been described. Although neoplasia and embedded larvae were observed sharing the common site affected by chronic inflammation, no association between the nematode and malignancy were directly proved. Similarly, no data are available about the effect of secretory and excretory products of infecting larvae at the host's cellular level, except in respect to allergenic interaction...
November 25, 2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27884606/bag3-is-a-modular-scaffolding-protein-that-physically-links-heat-shock-protein-70-hsp70-to-the-small-heat-shock-proteins
#15
Jennifer N Rauch, Eric Tse, Rebecca Freilich, Sue-Ann Mok, Leah N Makley, Daniel R Southworth, Jason E Gestwicki
Small heat shock proteins (sHsps) are a family of ATP-independent molecular chaperones that are important for binding and stabilizing unfolded proteins. In this task, the sHsps have been proposed to coordinate with ATP-dependent chaperones, including heat shock protein 70 (Hsp70). However, it isn't yet clear how these two important components of the chaperone network are linked. We report that the Hsp70 co-chaperone, BAG3, is a modular, scaffolding factor to bring together sHsps and Hsp70s. Using domain deletions and point mutations, we confirmed that BAG3 uses both of its IPV motifs to interact with sHsps, including Hsp27 (HspB1), αB-crystallin (HspB5), Hsp22 (HspB8) and Hsp20 (HspB6)...
November 21, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27882919/interaction-of-the-cotranslational-hsp70-ssb-with-ribosomal-proteins-and-rrna-depends-on-its-lid-domain
#16
Andrea Gumiero, Charlotte Conz, Genís Valentín Gesé, Ying Zhang, Felix Alexander Weyer, Karine Lapouge, Julia Kappes, Ulrike von Plehwe, Géza Schermann, Edith Fitzke, Tina Wölfle, Tamás Fischer, Sabine Rospert, Irmgard Sinning
Cotranslational chaperones assist in de novo folding of nascent polypeptides in all organisms. In yeast, the heterodimeric ribosome-associated complex (RAC) forms a unique chaperone triad with the Hsp70 homologue Ssb. We report the X-ray structure of full length Ssb in the ATP-bound open conformation at 2.6 Å resolution and identify a positively charged region in the α-helical lid domain (SBDα), which is present in all members of the Ssb-subfamily of Hsp70s. Mutational analysis demonstrates that this region is strictly required for ribosome binding...
November 24, 2016: Nature Communications
https://www.readbyqxmd.com/read/27881057/recent-patents-on-heat-shock-proteins-targeting-antibodies
#17
João Fernandes, Pedro Alves
BACKGROUND: Heat shock proteins (Hsp) are major chaperone molecules that have recently emerged as cancer therapeutic targets owing to their involvement in tumor cell proliferation, differentiation, invasion and metastasis. High levels of extracellular Hsp90 and Hsp70 have been closely associated with a wide range of human cancers. Accumulating evidence suggests that the pharmacological inhibition of these molecules can play a pivotal role in non-surgical cancer treatment. Efforts have been taken to develop monoclonal antibodies (mAbs) and antibody fragments targeting extracellular Hsp90 and Hsp70, alone or conjugated with standard anticancer agents, to control several types of cancer, such as breast, colon, prostate or melanoma...
November 23, 2016: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/27879259/unexpected-role-for-p19ink4d-in-post-transcriptional-regulation-of-gata1-and-modulation-of-human-terminal-erythropoiesis
#18
Xu Han, Jieying Zhang, Yuanliang Peng, Minyuan Peng, Xiao Chen, Huiyong Chen, Jianhui Song, Xiao Hu, Mao Ye, Jianglin Li, Vijay G Sankaran, Christopher D Hillyer, Narla Mohandas, Xiuli An, Jing Liu
Terminal erythroid differentiation is tightly coordinated with cell cycle exit, which is regulated by cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors (CDKI), yet their roles in erythropoiesis remain to be fully defined. We show here that p19(INK4d), a member of CDKI family, is abundantly expressed in erythroblasts and that p19(INK4d) knockdown delayed erythroid differentiation, inhibited cell growth, led to increased apoptosis and generation of abnormally nucleated late stage erythroblasts...
November 22, 2016: Blood
https://www.readbyqxmd.com/read/27878398/hsp90-is-a-promising-target-in-gemcitabine-and-5-fluorouracil-resistant-pancreatic-cancer
#19
Tarik Ghadban, Judith L Dibbern, Matthias Reeh, Jameel T Miro, Tung Y Tsui, Ulrich Wellner, Jakob R Izbicki, Cenap Güngör, Yogesh K Vashist
Chemotherapy (CT) options in pancreatic cancer (PC) are limited to gemcitabine and 5-fluorouracil (5-FU). Several identified molecular targets in PC represent client proteins of HSP90. HSP90 is a promising target since it interferes with many oncogenic signaling pathways simultaneously. The aim of this study was to evaluate the efficacy of different HSP90 inhibitors in gemcitabine and 5-FU resistant PC. PC cell lines 5061, 5072 and 5156 were isolated and brought in to culture from patients being operated at our institution...
November 22, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27876748/driving-pest-insect-populations-agricultural-chemicals-lead-to-an-adaptive-syndrome-in-nilaparvata-lugens-st%C3%A3-l-hemiptera-delphacidae
#20
Lin-Lin You, You Wu, Bing Xu, Jun Ding, Lin-Quan Ge, Guo-Qin Yang, Qi-Sheng Song, David Stanley, Jin-Cai Wu
The brown planthopper (BPH) is a devastating pest of rice throughout Asia. In this paper we document the BPH biogeographic range expansion in China over the 20-year period, 1992 to 2012. We posed the hypothesis that the range expansion is due to a syndrome of adaptations to the continuous presence of agricultural chemicals (insecticides and a fungicide) over the last 40 years. With respect to biogeography, BPH ranges have expanded by 13% from 1992 to 1997 and by another 3% from 1997 to 2012. In our view, such expansions may follow primarily from the enhancing effects of JGM, among other agricultural chemicals, and from global warming...
November 23, 2016: Scientific Reports
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