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https://www.readbyqxmd.com/read/29898735/microrna-644a-promotes-apoptosis-of-hepatocellular-carcinoma-cells-by-downregulating-the-expression-of-heat-shock-factor-1
#1
Wenjin Liang, Yong Liao, Zeming Li, Yan Wang, Siqi Zheng, Xiaochen Xu, Fulin Ran, Bo Tang, Zhenran Wang
In this study, we investigated the role of microRNA-644a (miR-644a) in the growth and survival of hepatocellular carcinoma (HCC) cells. MiR-644a levels were lower in HCC tissues than in adjacent peri-cancerous tissues (n = 135). MiR-644a expression was inversely correlated with heat shock factor 1 (HSF1) expression, tumour diameter and TNM stage. Moreover, HepG2 and SMMC-7721 cell lines showed lower miR-644a expression than normal L-O2 hepatocytes. MiR-644a overexpression in HepG2 and SMMC-7721 cells increased apoptosis by downregulating HSF1...
June 14, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29799521/heat-shock-factor-1-confers-resistance-to-lapatinib-in-erbb2-positive-breast-cancer-cells
#2
Alisha Yallowitz, Amr Ghaleb, Lucas Garcia, Evguenia M Alexandrova, Natalia Marchenko
Despite success of ERBB2-targeted therapies such as lapatinib, resistance remains a major clinical concern. Multiple compensatory receptor tyrosine kinase (RTK) pathways are known to contribute to lapatinib resistance. The heterogeneity of these adaptive responses is a significant hurdle for finding most effective combinatorial treatments. The goal of this study was to identify a unifying molecular mechanism whose targeting could help prevent and/or overcome lapatinib resistance. Using the MMTV-ERBB2;mutant p53 (R175H) in vivo mouse model of ERBB2-positive breast cancer, together with mouse and human cell lines, we compared lapatinib-resistant vs...
May 24, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29792912/heat-shock-protein-b1-is-required-for-the-prolactin-induced-cytoprotective-effects-on-pancreatic-islets
#3
Rosangela Am Wailemann, Letícia F Terra, Talita C de Oliveira, Ancély F Dos Santos, Vinícius M Gomes, Leticia Labriola
The success of islet transplantation has improved lately. Unfortunately, it is still compromised by cell loss. We have shown that prolactin (PRL) inhibits beta-cell apoptosis and up-regulates the antiapoptotic Heat Shock Protein B1 (HSPB1) in human islets. Since its function in pancreatic islets has not been studied, we explored the role of HSPB1 in PRL-induced beta-cell survival. The significant PRL-induced cytoprotection in control cells was abrogated in HSPB1 silenced cells, overexpression of HSPB1 recovered survival...
May 21, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29788061/regulation-of-the-heat-shock-transcription-factor-hsf1-in-fungi-implications-for-temperature-dependent-virulence-traits
#4
Amanda O Veri, Nicole Robbins, Leah E Cowen
The impact of fungal pathogens on human health is devastating. For fungi and other pathogens, a key determinant of virulence is the capacity to thrive at host temperatures, with elevated temperature in the form of fever as a ubiquitous host response to defend against infection. A prominent feature of cells experiencing heat stress is the increased expression of heat shock proteins (Hsps) that play pivotal roles in the refolding of misfolded proteins in order to restore cellular homeostasis. Transcriptional activation of this heat shock response is orchestrated by the essential heat shock transcription factor, Hsf1...
August 1, 2018: FEMS Yeast Research
https://www.readbyqxmd.com/read/29774376/roles-of-heat-shock-factor-1-beyond-the-heat-shock-response
#5
REVIEW
János Barna, Péter Csermely, Tibor Vellai
Various stress factors leading to protein damage induce the activation of an evolutionarily conserved cell protective mechanism, the heat shock response (HSR), to maintain protein homeostasis in virtually all eukaryotic cells. Heat shock factor 1 (HSF1) plays a central role in the HSR. HSF1 was initially known as a transcription factor that upregulates genes encoding heat shock proteins (HSPs), also called molecular chaperones, which assist in refolding or degrading injured intracellular proteins. However, recent accumulating evidence indicates multiple additional functions for HSF1 beyond the activation of HSPs...
May 17, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29762687/glycine-treatment-enhances-developmental-potential-of-porcine-oocytes-and-early-embryos-by-inhibiting-apoptosis
#6
Suo Li, Qing Guo, Yu-Meng Wang, Zi-Yue Li, Jin-Dan Kang, Xi-Jun Yin, Xin Zheng
Glycine, a component of glutathione (GSH), plays an important role in protection from reactive oxygen species (ROS) and inhibition of apoptosis. The aim of this study was to determine the effect of glycine on in vitro maturation (IVM) of porcine oocytes and their developmental competence after parthenogenetic activation (PA). We examined nuclear maturation, ROS levels, apoptosis, mitochondrial membrane potential (ΔΨm), and ATP concentration, as well as the expression of several genes related to oocyte maturation and development...
May 12, 2018: Journal of Animal Science
https://www.readbyqxmd.com/read/29759983/high-throughput-discovery-of-functional-disordered-regions-investigation-of-transactivation-domains
#7
Charles Nj Ravarani, Tamara Y Erkina, Greet De Baets, Daniel C Dudman, Alexandre M Erkine, M Madan Babu
Over 40% of proteins in any eukaryotic genome encode intrinsically disordered regions (IDRs) that do not adopt defined tertiary structures. Certain IDRs perform critical functions, but discovering them is non-trivial as the biological context determines their function. We present IDR-Screen, a framework to discover functional IDRs in a high-throughput manner by simultaneously assaying large numbers of DNA sequences that code for short disordered sequences. Functionality-conferring patterns in their protein sequence are inferred through statistical learning...
May 14, 2018: Molecular Systems Biology
https://www.readbyqxmd.com/read/29757368/the-long-noncoding-rna-landscape-of-neuroendocrine-prostate-cancer-and-its-clinical-implications
#8
Varune Rohan Ramnarine, Mohammed Alshalalfa, Fan Mo, Noushin Nabavi, Nicholas Erho, Mandeep Takhar, Robert Shukin, Sonal Brahmbhatt, Alexander Gawronski, Maxim Kobelev, Mannan Nouri, Dong Lin, Harrison Tsai, Tamara L Lotan, R Jefferey Karnes, Mark A Rubin, Amina Zoubeidi, Martin E Gleave, Cenk Sahinalp, Alexander W Wyatt, Stanislav V Volik, Himisha Beltran, Elai Davicioni, Yuzhuo Wang, Colin C Collins
Background: Treatment induced neuroendocrine prostate cancer (tNEPC) is an aggressive variant of late-stage metastatic castrate resistant (mCRPC) prostate cancer that commonly arises through neuroendocrine transdifferentiation (NEtD). Treatment options are limited, ineffective, and for most patients, results in death in less than a year. We previously developed a first-in-field patient-derived xenograft (PDX) model of NEtD. Longitudinal deep transcriptome profiling of this model enabled monitoring of dynamic transcriptional changes during NEtD and in the context of androgen deprivation...
May 10, 2018: GigaScience
https://www.readbyqxmd.com/read/29752334/tg2-regulates-the-heat-shock-response-by-the-post-translational-modification-of-hsf1
#9
Federica Rossin, Valeria Rachela Villella, Manuela D'Eletto, Maria Grazia Farrace, Speranza Esposito, Eleonora Ferrari, Romina Monzani, Luca Occhigrossi, Vittoria Pagliarini, Claudio Sette, Giorgio Cozza, Nikolai A Barlev, Laura Falasca, Gian Maria Fimia, Guido Kroemer, Valeria Raia, Luigi Maiuri, Mauro Piacentini
Heat-shock factor 1 (HSF1) is the master transcription factor that regulates the response to proteotoxic stress by controlling the transcription of many stress-responsive genes including the heat-shock proteins. Here, we show a novel molecular mechanism controlling the activation of HSF1. We demonstrate that transglutaminase type 2 (TG2), dependent on its protein disulphide isomerase activity, triggers the trimerization and activation of HSF1 regulating adaptation to stress and proteostasis impairment. In particular, we find that TG2 loss of function correlates with a defect in the nuclear translocation of HSF1 and in its DNA-binding ability to the HSP70 promoter...
May 11, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29750253/transport-stress-induces-heart-damage-in-newly-hatched-chicks-via-blocking-the-cytoprotective-heat-shock-response-and-augmenting-nitric-oxide-production
#10
F Sun, Y-Z Zuo, J Ge, J Xia, X-N Li, J Lin, C Zhang, H-L Xu, J-L Li
Transport stress affects the animal's metabolism and psychological state. As a pro-survival pathway, the heat shock response (HSR) protects healthy cells from stressors. However, it is unclear whether the HSR plays a role in transport stress-induced heart damage. To evaluate the effects of transport stress on heart damage and HSR protection, newly hatched chicks were treated with transport stress for 2 h, 4 h and 8 h. Transport stress caused decreases in body weight and increases in serum creatine kinase (CK) activity, nitric oxide (NO) content in heart tissue, cardiac nitric oxide syntheses (NOS) activity and NOS isoforms transcription...
April 20, 2018: Poultry Science
https://www.readbyqxmd.com/read/29734798/the-disordered-c-terminus-of-yeast-hsf1-contains-a-cryptic-low-complexity-amyloidogenic-region
#11
Jordi Pujols, Jaime Santos, Irantzu Pallarès, Salvador Ventura
Response mechanisms to external stress rely on networks of proteins able to activate specific signaling pathways to ensure the maintenance of cell proteostasis. Many of the proteins mediating this kind of response contain intrinsically disordered regions, which lack a defined structure, but still are able to interact with a wide range of clients that modulate the protein function. Some of these interactions are mediated by specific short sequences embedded in the longer disordered regions. Because the physicochemical properties that promote functional and abnormal interactions are similar, it has been shown that, in globular proteins, aggregation-prone and binding regions tend to overlap...
May 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29733381/the-longevity-snp-rs2802292-uncovered-hsf1-activates-stress-dependent-expression-of-foxo3-through-an-intronic-enhancer
#12
Valentina Grossi, Giovanna Forte, Paola Sanese, Alessia Peserico, Tugsan Tezil, Martina Lepore Signorile, Candida Fasano, Rosaura Lovaglio, Rosanna Bagnulo, Daria C Loconte, Francesco C Susca, Nicoletta Resta, Cristiano Simone
The HSF and FOXO families of transcription factors play evolutionarily conserved roles in stress resistance and lifespan. In humans, the rs2802292 G-allele at FOXO3 locus has been associated with longevity in all human populations tested; moreover, its copy number correlated with reduced frequency of age-related diseases in centenarians. At the molecular level, the intronic rs2802292 G-allele correlated with increased expression of FOXO3, suggesting that FOXO3 intron 2 may represent a regulatory region. Here we show that the 90-bp sequence around the intronic single nucleotide polymorphism rs2802292 has enhancer functions, and that the rs2802292 G-allele creates a novel HSE binding site for HSF1, which induces FOXO3 expression in response to diverse stress stimuli...
May 4, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29730197/heat-shock-factor-1-epigenetically-stimulates-glutaminase-1-dependent-mtor-activation-to-promote-colorectal-carcinogenesis
#13
Jiaqiu Li, Ping Song, Tingting Jiang, Dongjun Dai, Hanying Wang, Jie Sun, Liyuan Zhu, Wenxia Xu, Lifeng Feng, Vivian Y Shin, Helen Morrison, Xian Wang, Hongchuan Jin
Heat shock factor 1 (HSF1) generally exhibits its properties under stress conditions. In tumors, HSF1 has a pleiotropic feature in regulating growth, survival, and aggressiveness of cancer cells. In this study, we found HSF1 was increased in colorectal cancer (CRC) and had a positive correlation with shorter disease-free survival (DFS). Knockdown of HSF1 in CRC cells attenuated their growth while inhibiting mTOR activation and glutamine metabolism. HSF1 inhibited the expression of microRNA137 (MIR137), which targeted GLS1 (glutaminase 1), thus stimulating GLS1 protein expression to promote glutaminolysis and mTOR activation...
April 14, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29725069/hsp90-inhibitors-disrupt-a-transient-hsp90-hsf1-interaction-and-identify-a-noncanonical-model-of-hsp90-mediated-hsf1-regulation
#14
Toshiki Kijima, Thomas L Prince, Megan L Tigue, Kendrick H Yim, Harvey Schwartz, Kristin Beebe, Sunmin Lee, Marek A Budzynski, Heinric Williams, Jane B Trepel, Lea Sistonen, Stuart Calderwood, Len Neckers
Heat shock factor 1 (HSF1) initiates a broad transcriptional response to proteotoxic stress while also mediating a cancer-specific transcriptional program. HSF1 is thought to be regulated by molecular chaperones, including Heat Shock Protein 90 (HSP90). HSP90 is proposed to sequester HSF1 in unstressed cells, but visualization of this interaction in vivo requires protein crosslinking. In this report, we show that HSP90 binding to HSF1 depends on HSP90 conformation and is only readily visualized for the ATP-dependent, N-domain dimerized chaperone, a conformation only rarely sampled by mammalian HSP90...
May 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29720454/data-driven-dynamical-model-indicates-that-the-heat-shock-response-in-chlamydomonas-reinhardtii-is-tailored-to-handle-natural-temperature-variation
#15
Stefano Magni, Antonella Succurro, Alexander Skupin, Oliver Ebenhöh
Global warming exposes plants to severe heat stress, with consequent crop yield reduction. Organisms exposed to high temperature stresses typically protect themselves with a heat shock response (HSR), where accumulation of unfolded proteins initiates the synthesis of heat shock proteins through the heat shock transcription factor HSF1. While the molecular mechanisms are qualitatively well characterized, our quantitative understanding of the underlying dynamics is still very limited. Here, we study the dynamics of HSR in the photosynthetic model organism Chlamydomonas reinhardtii with a data-driven mathematical model of HSR...
May 2018: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29715263/downregulation-of-mir-199b-5p-inducing-differentiation-of-bone-marrow-mesenchymal-stem-cells-bmscs-toward-cardiomyocyte-like-cells-via-hsf1-hsp70-pathway
#16
Fangjie Dai, Peizhao Du, Yaowei Chang, Endong Ji, Yunjia Xu, Chunyan Wei, Jiming Li
BACKGROUND Bone-marrow mesenchymal stem cells (BMSCs) are pluripotent stem cells with potent self-renewal and differentiation ability that are widely used in transplantation of cell therapy. But the mechanism on microRNA (miRNA) regulating stem cell differentiation is complicated and unclear. The aim of this study was to investigate whether miR-199b-5p is involved in differentiation of cardiomyocyte-like cells and identify potential signal pathways in BMSCs. MATERIAL AND METHODS Mouse BMSCs were treated with 5-azacytidine and transfected by miR-199b-5p mimic and inhibitor, respectively...
May 1, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29710398/phenethyl-isothiocyanate-a-dual-activator-of-transcription-factors-nrf2-and-hsf1
#17
REVIEW
Sharadha Dayalan Naidu, Takafumi Suzuki, Masayuki Yamamoto, Jed W Fahey, Albena T Dinkova-Kostova
Cruciferous vegetables are rich sources of glucosinolates which are the biogenic precursor molecules of isothiocyanates (ITCs). The relationship between the consumption of cruciferous vegetables and chemoprotection has been widely documented in epidemiological studies. Phenethyl isothiocyanate (PEITC) occurs as its glucosinolate precursor gluconasturtiin in the cruciferous vegetable watercress (Nasturtium officinale). PEITC has multiple biological effects, including activation of cytoprotective pathways, such as those mediated by the transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2) and the transcription factor heat shock factor 1 (HSF1), and can cause changes in the epigenome...
April 30, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29704482/new-hsf1-inducer-as-a-therapeutic-agent-in-a-rodent-model-of-parkinson-s-disease
#18
Irina V Ekimova, Daria V Plaksina, Yuri F Pastukhov, Ksenia V Lapshina, Vladimir F Lazarev, Elena R Mikhaylova, Sergey G Polonik, Bibhusita Pani, Boris A Margulis, Irina V Guzhova, Evgeny Nudler
Molecular chaperone HSP70 (HSPA1A) has therapeutic potential in conformational neurological diseases. Here we evaluate the neuroprotective function of the chaperone in a rat model of Parkinson's disease (PD). We show that the knock-down of HSP70 (HSPA1A) in dopaminergic neurons of the Substantia nigra causes an almost 2-fold increase in neuronal death and multiple motor disturbances in animals. Conversely, pharmacological activation of HSF1 transcription factor and enhanced expression of inducible HSP70 with the echinochrome derivative, U-133, reverses the process of neurodegeneration, as evidenced by а increase in the number of tyrosine hydroxylase-containing neurons, and prevents the motor disturbances that are typical of the clinical stage of the disease...
August 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29678661/role-of-heat-shock-transcription-factor-1-hsf1-upregulated-macrophage-in-ameliorating-pressure-overload-induced-heart-failure-in-mice
#19
Peizhao Du, Yaowei Chang, Fangjie Dai, Chunyan Wei, Qi Zhang, Jiming Li
In order to explore the role of macrophages in HSF1-mediated alleviation of heart failure, mice model of pressure overload-induced heart failure was established using transverse aortic constriction (TAC). Changes in cardiac function and morphology were studied in TAC and SHAM groups using ultrasonic device, tissue staining, electron microscopy, real-time quantitative polymerase chain reaction (RT-QPCR), and Western blotting. We found that mice in the TAC group showed evidence of impaired cardiac function and aggravation of fibrosis on ultrasonic and histopathological examination when compared to those in the SHAM group...
August 15, 2018: Gene
https://www.readbyqxmd.com/read/29674963/a-bivalent-securinine-compound-sn3-l6-induces-neuronal-differentiation-via-translational-upregulation-of-neurogenic-transcription-factors
#20
Yumei Liao, Xiaoji Zhuang, Xiaojie Huang, Yinghui Peng, Xuanyue Ma, Zhi-Xing Huang, Feng Liu, Junyu Xu, Ying Wang, Wei-Min Chen, Wen-Cai Ye, Lei Shi
Developing therapeutic approaches that target neuronal differentiation will be greatly beneficial for the regeneration of neurons and synaptic networks in neurological diseases. Protein synthesis (mRNA translation) has recently been shown to regulate neurogenesis of neural stem/progenitor cells (NSPCs). However, it has remained unknown whether engineering translational machinery is a valid approach for manipulating neuronal differentiation. The present study identifies that a bivalent securinine compound SN3-L6, previously designed and synthesized by our group, induces potent neuronal differentiation through a novel translation-dependent mechanism...
2018: Frontiers in Pharmacology
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