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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
#1
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...
April 17, 2018: Gene
https://www.readbyqxmd.com/read/29674963/a-bivalent-securinine-compound-sn3-l6-induces-neuronal-differentiation-via-translational-upregulation-of-neurogenic-transcription-factors
#2
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
https://www.readbyqxmd.com/read/29661921/parp1-promotes-the-human-heat-shock-response-by-facilitating-hsf1-binding-to-dna
#3
Mitsuaki Fujimoto, Ryosuke Takii, Arpit Katiyar, Pratibha Srivastava, Akira Nakai
The heat shock response (HSR) is characterized by the rapid and robust induction of heat shock proteins (HSPs), including HSP70, in response to heat shock, and is regulated by heat shock transcription factor 1 (HSF1) in mammalian cells. Poly(ADP-ribose) polymerase 1 (PARP1), which can form a complex with HSF1 through the scaffold protein PARP13, has been suggested to be involved in the HSR. However, its effects on and regulatory mechanisms of the HSR are not well understood. Here, we show that prior to heat shock the HSF1-PARP13-PARP1 complex binds to HSP70 promoter...
April 16, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29661622/rational-design-and-screening-of-peptide-based-inhibitors-of-heat-shock-factor-1-hsf1
#4
Xu Ran, Eileen T Burchfiel, Bushu Dong, Nicholas J Rettko, Bryan M Dunyak, Hao Shao, Dennis J Thiele, Jason E Gestwicki
Heat shock factor 1 (HSF1) is a stress-responsive transcription factor that regulates expression of protein chaperones and cell survival factors. In cancer, HSF1 plays a unique role, hijacking the normal stress response to drive a cancer-specific transcriptional program. These observations suggest that HSF1 inhibitors could be promising therapeutics. However, HSF1 is activated through a complex mechanism, which involves release of a negative regulatory domain, leucine zipper 4 (LZ4), from a masked oligomerization domain (LZ1-3), and subsequent binding of the oligomer to heat shock elements (HSEs) in HSF1-responsive genes...
April 7, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29660399/cacybp-sip-a-hsp90-binding-chaperone-in-cellular-stress-response
#5
Agnieszka Góral, Katarzyna Bartkowska, Rouzanna L Djavadian, Anna Filipek
CacyBP/SIP interacts with Hsp90 and is able to protect proteins from denaturation and/or aggregation induced by elevated temperature. In this work we studied the influence of different stress factors on CacyBP/SIP level in HEp-2 cells. We have found that H2 O2 and radicicol treatment resulted in a significant increase (up to 40-50%) in the CacyBP/SIP level. We have also found that HEp-2 cells overexpressing CacyBP/SIP were more resistant to stress-induced death. Further studies have revealed that the Hsf1 transcription factor binds to the CacyBP/SIP gene promoter and up-regulates CacyBP/SIP expression under stress conditions...
April 13, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29626503/hsf1-deficiency-accelerates-the-transition-from-pressure-overload-induced-cardiac-hypertrophy-to-heart-failure-through-endothelial-mir-195a-3p-mediated-impairment-of-cardiac-angiogenesis
#6
Shijun Wang, Jian Wu, Jieyun You, Hongyu Shi, Xiaoyu Xue, Jiayuan Huang, Lei Xu, Guoliang Jiang, Lingyan Yuan, Xue Gong, Haiyan Luo, Junbo Ge, Zhaoqiang Cui, Yunzeng Zou
Heat shock transcription factor 1 (HSF1) deficiency aggravates cardiac remodeling under pressure overload. However, the mechanism is still unknown. Here we employed microRNA array analysis of the heart tissue of HSF1-knockout (KO) mice to investigate the potential roles of microRNAs in pressure overload-induced cardiac remodeling under HSF-1 deficiency, and the profiles of 478 microRNAs expressed in the heart tissues of adult HSF1-KO mice were determined. We found that the expression of 5 microRNAs was over 2-fold higher expressed in heart tissues of HSF1-KO mice than in those of wild-type (WT) control mice...
April 4, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29606348/gkap-acts-as-a-genetic-modulator-of-nmdar-signaling-to-govern-invasive-tumor-growth
#7
Leanne Li, Qiqun Zeng, Arjun Bhutkar, José A Galván, Eva Karamitopoulou, Daan Noordermeer, Mei-Wen Peng, Alessandra Piersigilli, Aurel Perren, Inti Zlobec, Hugh Robinson, M Luisa Iruela-Arispe, Douglas Hanahan
Genetic linkage analysis previously suggested that GKAP, a scaffold protein of the N-methyl-D-aspartate receptor (NMDAR), was a potential modifier of invasion in a mouse model of pancreatic neuroendocrine tumor (PanNET). Here, we establish that GKAP governs invasive growth and treatment response to NMDAR inhibitors of PanNET via its pivotal role in regulating NMDAR pathway activity. Combining genetic knockdown of GKAP and pharmacological inhibition of NMDAR, we implicate as downstream effectors FMRP and HSF1, which along with GKAP demonstrably support invasiveness of PanNET and pancreatic ductal adenocarcinoma cancer cells...
March 9, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29605660/stressed-out-mitohormesis-is-crossing-borders
#8
André Franz, Thorsten Hoppe
Labbadia et al. showed that low-dose mitochondrial stress promotes protein homeostasis in the cytosol to endure proteotoxic conditions, particularly during aging. This hormetic mitochondrial stress response is heat shock factor 1 (HSF1)-dependent and, remarkably, does not affect physiological parameters that are usually associated with pathogenic disturbance of mitochondrial function.
March 28, 2018: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29590106/tuning-hsf1-levels-drives-distinct-fungal-morphogenetic-programs-with-depletion-impairing-hsp90-function-and-overexpression-expanding-the-target-space
#9
Amanda O Veri, Zhengqiang Miao, Rebecca S Shapiro, Faiza Tebbji, Teresa R O'Meara, Sang Hu Kim, Juan Colazo, Kaeling Tan, Valmik K Vyas, Malcolm Whiteway, Nicole Robbins, Koon Ho Wong, Leah E Cowen
The capacity to respond to temperature fluctuations is critical for microorganisms to survive within mammalian hosts, and temperature modulates virulence traits of diverse pathogens. One key temperature-dependent virulence trait of the fungal pathogen Candida albicans is its ability to transition from yeast to filamentous growth, which is induced by environmental cues at host physiological temperature. A key regulator of temperature-dependent morphogenesis is the molecular chaperone Hsp90, which has complex functional relationships with the transcription factor Hsf1...
March 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29571878/expression-analysis-of-protein-homeostasis-pathways-in-the-peripheral-blood-mononuclear-cells-of-sporadic-amyotrophic-lateral-sclerosis-patients
#10
Abhishek Vats, Mandaville Gourie-Devi, Kavita Ahuja, Ankkita Sharma, Saima Wajid, Nirmal Kumar Ganguly, Vibha Taneja
Misfolded protein aggregates are the hallmark of Amyotrophic Lateral Sclerosis (ALS) which suggests involvement of protein homeostasis pathways in etiology of ALS. However, status of protein homeostasis in peripheral blood of ALS is not well established. We analyzed expression levels of key genes of proteostasis pathways in peripheral blood mononuclear cells (PBMCs) of sporadic ALS (sALS) patients and healthy controls. Increased protein carbonylation was observed in patients reflecting oxidative damage in PBMCs...
April 15, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29562166/hsf1-phosphorylation-generates-cell-to-cell-variation-in-hsp90-levels-and-promotes-phenotypic-plasticity
#11
Xu Zheng, Ali Beyzavi, Joanna Krakowiak, Nikit Patel, Ahmad S Khalil, David Pincus
Clonal populations of cells exhibit cell-to-cell variation in the transcription of individual genes. In addition to this noise in gene expression, heterogeneity in the proteome and the proteostasis network expands the phenotypic diversity of a population. Heat shock factor 1 (Hsf1) regulates chaperone gene expression, thereby coupling transcriptional noise to proteostasis. Here we show that cell-to-cell variation in Hsf1 activity is an important determinant of phenotypic plasticity. Budding yeast cells with high Hsf1 activity were enriched for the ability to acquire resistance to an antifungal drug, and this enrichment depended on Hsp90, a known phenotypic capacitor and canonical Hsf1 target...
March 20, 2018: Cell Reports
https://www.readbyqxmd.com/read/29541415/sensitization-of-multidrug-resistant-cancer-cells-to-hsp90-inhibitors-by-nsaids-induced-apoptotic-and-autophagic-cell-death
#12
Hyun-Jung Moon, Hak-Bong Kim, Su-Hoon Lee, So-Eun Jeun, Chi-Dug Kang, Sun-Hee Kim
NSAIDs (non-steroidal anti-inflammatory drugs) have potential use as anticancer agents, either alone or in combination with other cancer therapies. We found that NSAIDs including celecoxib (CCB) and ibuprofen (IBU) significantly potentiated the cytotoxicity of Hsp90 inhibitors in human multidrug-resistant (MDR) cells expressing high levels of mutant p53 (mutp53) protein and P-glycoprotein (P-gp), and reversed Hsp90 inhibitor resistance caused by activation of heat shock factor 1 (HSF1) and by up-regulation of heat shock proteins (Hsps) and P-gp...
February 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/29525181/heat-shock-factor-1-suppresses-the-hiv-induced-inflammatory-response-by-inhibiting-nuclear-factor-%C3%AE%C2%BAb
#13
Xiaoyan Pan, Jian Lin, Xiaoyun Zeng, Wenjuan Li, Wenjiao Wu, Wan Zhen Lu, Jing Liu, Shuwen Liu
The persistent inflammation aggravated by a disordered immune response is considered to be the major cause of CD4+ T cell depletion in lymphoid tissue, which impels the progression of AIDS. Here, we report that heat shock factor 1 (HSF1) works as an innate repressor of HIV-induced inflammation. The activation of HSF1 was found to accompany inflammation during HIV infection. Further research uncovered that HSF1 activation inhibited HIV-induced inflammation. In addition, HSF1 overexpression suppressed the inflammatory response induced by HIV, while HSF1 deficiency exacerbated that inflammation...
January 31, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29509048/zhsf1-modulates-zper2-expression-in-zebrafish-embryos
#14
Lucas Mennetrier, Tatiana Lopez, Benoist Pruvot, Nadhir Yousfi, Olivier Armant, Hanae Hazhaz, Vincent Lhuissiez, Carmen Garrido, Johanna Chluba
HSF1 is a transcription factor that plays a key role in circadian resetting by temperature. We have used zebrafish embryos to decipher the roles of zHsf1, heat and light on zper2 transcription in vivo. Our results show that heat shock (HS) stimulated zper2 expression in the dark but has no cumulative effect combined with light. After light exposition, zper2 expression was 2.7 fold increased threefold in the hsf1-morphants in comparison to control embryos. Our results show that zHsf1 plays a positive role in HS-driven expression of zper2 in the dark but seems to act as an attenuator in the presence light...
March 6, 2018: Chronobiology International
https://www.readbyqxmd.com/read/29494616/genetic-polymorphism-and-expression-of-hsf1-gene-is-significantly-associated-with-breast-cancer-in-saudi-females
#15
Sahar Almotwaa, Mohamed Elrobh, Huda AbdulKarim, Mohamed Alanazi, Sooad Aldaihan, Jilani Shaik, Maha Arafa, Arjumand Sultan Warsy
The transcription factor, heat shock factor 1 (HSF1), influences the expression of heat shock proteins as well as other activities like the induction of tumor suppressor genes, signal transduction pathway, and glucose metabolism. We hypothesized that single nucleotide polymorphisms (SNPs) in HSF1 gene might affect its expression or function which might have an influence on the development of breast cancer. The study group included 242 individuals (146 breast cancer patients and 96 healthy controls). From the cancer patients, genomic DNA was extracted from 96 blood samples and 50 Formalin-Fixed Paraffin Embedded (FFPE) tissues, while from the controls DNA were extracted from blood only...
2018: PloS One
https://www.readbyqxmd.com/read/29486577/proteomic-analysis-identifies-nptx1-and-hip1r-as-potential-targets-of-histone-deacetylase-3-mediated-neurodegeneration
#16
Zhe Qu, Santosh R D'Mello
A defining feature of neurodegenerative diseases is the abnormal and excessive loss of neurons. One molecule that is particularly important in promoting neuronal death in a variety of cell culture and in vivo models of neurodegeneration is histone deacetylase-3 (HDAC3), a member of the histone deacetylase family of proteins. As a step towards understanding how HDAC3 promotes neuronal death, we conducted a proteomic screen aimed at identifying proteins that were regulated by HDAC3. HDAC3 was overexpressed in cultured rat cerebellar granule neurons (CGNs) and protein lysates were analyzed by mass spectrometry...
January 1, 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29447393/disruption-of-spt23-results-in-increased-heat-sensitivity-due-to-plasma-membrane-damage-in-pichia-pastoris
#17
Meng Zhang, Qilin Yu, Chenpeng Xiao, Kai Zhang, Dan Zhang, Biao Zhang, Mingchun Li
The ability to adapt to environmental changes is the necessary strategy of cell survival. Spt23 is responsible for regulation of Δ-9 desaturase expression in Pichia pastoris. Disruption of SPT23 leads to a remarkable decrease in cellular unsaturated fatty acids. In this study, we found that deletion of SPT23 resulted in growth defect under high temperature culture conditions and heat treatment induced the expression of SPT23. By measuring expression changes of heat shock proteins, protein levels and cellular localization of Hsf1, it revealed that the sensitivity of spt23Δ to high temperature was independent of heat shock response...
February 13, 2018: FEMS Yeast Research
https://www.readbyqxmd.com/read/29444801/widespread-and-precise-reprogramming-of-yeast-protein-genome-interactions-in-response-to-heat-shock
#18
Vinesh Vinayachandran, Rohit Reja, Matthew J Rossi, Bongsoo Park, Lila Rieber, Chitvan Mittal, Shaun Mahony, B Franklin Pugh
Gene expression is controlled by a variety of proteins that interact with the genome. Their precise organization and mechanism of action at every promoter remains to be worked out. To better understand the physical interplay among genome-interacting proteins, we examined the temporal binding of a functionally diverse subset of these proteins: nucleosomes (H3), H2AZ (Htz1), SWR (Swr1), RSC (Rsc1, Rsc3, Rsc58, Rsc6, Rsc9, Sth1), SAGA (Spt3, Spt7, Ubp8, Sgf11), Hsf1, TFIID (Spt15/TBP and Taf1), TFIIB (Sua7), TFIIH (Ssl2), FACT (Spt16), Pol II (Rpb3), and Pol II carboxyl-terminal domain (CTD) phosphorylation at serines 2, 5, and 7...
February 14, 2018: Genome Research
https://www.readbyqxmd.com/read/29440176/targeting-hsf1-a-prime-integrator-of-proteotoxic-stress-response-in-myeloma
#19
Samir Parekh
The HSF1 transcription factor is an integrator of the cellular stress response and its expression has demonstrated poor prognosis in multiple myeloma. Novel anti-HSF1 small molecule inhibitors CCT251236 and KRIB11 demonstrate in vitro and in vivo anti-myeloma activity, representing a novel approach for targeting the heat shock response in myeloma.
February 9, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29421151/fractional-excretion-as-a-new-marker-of-tubular-damage-in-children-with-chronic-kidney-disease
#20
Kinga Musiał, Danuta Zwolińska
OBJECTIVES: Vitamin D-binding protein (VDBP), retinol-binding protein (RBP)4, and heat shock proteins (hsp) are markers of tubular function and apoptosis, accompanying chronic kidney disease (CKD) from its earliest stages. Fractional excretion of proteins with urine is a marker of tubular damage. The aim of study was to assess the usefulness of fractional excretion (FE) of VDBP, RBP4, HSF1 and Hsp27 as markers of tubular damage in the course of CKD. METHODS: The study group consisted of 70 children with CKD stages 1-5, treated conservatively, and 12 age-matched controls with normal kidney function...
February 6, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
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