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Jie Meng, Wen-Xiong Wang, Li Li, Guofan Zhang
Lead (Pb) is one of the ubiquitous and toxic elements in aquatic environment. In oysters, gills and digestive glands are the main target organs for Pb-induced toxicity, but there is limited information on the molecular mechanisms underlying its toxicity. The present study investigated the Pb-induced toxicity mechanisms in the Pacific oyster (Crassostrea gigas) based on transcriptome, phenotypic anchoring, and validation of targeted gene expression. Gene ontology and pathway enrichment analyses revealed the differential Pb toxicity mechanisms in the tissues...
March 13, 2018: Aquatic Toxicology
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
Marcello Ceci, Claudia Carlantoni, Maria Azzurra Missinato, Davide Bonvissuto, Bruna Di Giacomo, Riccardo Contu, Nicla Romano
Zebrafish could be an interesting translational model to understand and improve the post-infarction trial and possible regeneration in humans. The adult zebrafish is able to regenerate efficiently after resecting nearly 20% of the ventricular apex. This process requires the concert activation of the epicardium and endocardium, as well as trans-differentiation of pre-existing cardiomyocytes that together replace the lost tissue. The molecular mechanisms involved in this activation process are not completely clarified...
2018: Cell Death Discovery
Ahmad Al-Attar, Steven R Presnell, Jody L Clasey, Douglas E Long, R Grace Walton, Morgan Sexton, Marlene E Starr, Philip A Kern, Charlotte A Peterson, Charles T Lutz
Natural killer (NK) lymphocyte-mediated cytotoxicity and cytokine secretion control infections and cancers, but these crucial activities decline with age. NK cell development, homeostasis, and function require IL-15 and its chaperone, IL-15 receptor alpha (IL-15Rα). Macrophages and dendritic cells (DC) are major sources of these proteins. We had previously postulated that additional IL-15 and IL-15Rα is made by skeletal muscle and adipose tissue. These sources may be important in aging, when IL-15-producing immune cells decline...
2018: Frontiers in Immunology
Philip E B Nickerson, Arturo Ortin-Martinez, Valerie A Wallace
Considerable research effort has been invested into the transplantation of mammalian photoreceptors into healthy and degenerating mouse eyes. Several platforms of rod and cone fluorescent reporting have been central to refining the isolation, purification and transplantation of photoreceptors. The tracking of engrafted cells, including identifying the position, morphology and degree of donor cell integration post-transplant is highly dependent on the use of fluorescent protein reporters. Improvements in imaging and analysis of transplant recipients have revealed that donor cell fluorescent reporters can transfer into host tissue though a process termed material exchange (ME)...
2018: Frontiers in Neural Circuits
Cong Liu, Xiufen Liu, Jing Qi, Om Prakash Pant, Cheng-Wei Lu, Jilong Hao
Protein deglycase DJ-1 (Parkinson disease protein 7) is a 20 kDa protein encoded by PARK7 gene. It is also known as a redox-sensitive chaperone and sensor that protect cells against oxidative stress-induced cell death in many human diseases. Though increasing evidence implicates that DJ-1 may also participate in ocular diseases, the overview of DJ-1 in ocular diseases remains elusive. In this review, we discuss the role as well as the underlying molecular mechanisms of DJ-1 in ocular diseases, including Fuchs endothelial corneal dystrophy (FECD), age-related macular degeneration (AMD), cataracts, and ocular neurodegenerative diseases, highlighting that DJ-1 may serve as a very striking therapeutic target for ocular diseases...
2018: International Journal of Medical Sciences
Tianhong Su, Junbin Liao, Zihao Dai, Lixia Xu, Shuling Chen, Yifei Wang, Zhenwei Peng, Qiuyang Zhang, Sui Peng, Ming Kuang
Recent studies indicated that insufficient radiofrequency ablation (RFA) could endow hepatocellular carcinoma (HCC) with higher aggressive potential. Stress-induced phosphoprotein 1 (STIP1), which was found highly expressed in HCC, is a chaperone molecule mediating cell homeostasis under thermal stress. We aimed to explore the role of STIP1 on the metastasis of residual HCC after RFA. Mice model with orthotopic HCC implants or caudal vein injection were employed to assess potential of lung metastasis and/or intrahepatic metastasis (IHM) of HCC cells...
March 21, 2018: Oncogene
María Del Pino, Amado Andrés, Ana Ávila Bernabéu, Joaquín de Juan-Rivera, Elvira Fernández, Juan de Dios García Díaz, Domingo Hernández, José Luño, Isabel Martínez Fernández, José Paniagua, Manuel Posada de la Paz, José Carlos Rodríguez-Pérez, Rafael Santamaría, Roser Torra, Joan Torras Ambros, Pedro Vidau, Josep-Vicent Torregrosa
Fabry disease (FD) is a rare, X-linked disorder caused by mutations in the GLA gene encoding the enzyme α-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, endothelial cells, epithelial cells, and tubular cells contribute to the renal symptoms of FD, which manifest as proteinuria and reduced glomerular filtration rate leading to renal insufficiency...
March 16, 2018: Kidney & Blood Pressure Research
Daniel Mattle, Bernd Kuhn, Johannes Aebi, Marc Bedoucha, Demet Kekilli, Nathalie Grozinger, Andre Alker, Markus G Rudolph, Georg Schmid, Gebhard F X Schertler, Michael Hennig, Jörg Standfuss, Roger J P Dawson
In the degenerative eye disease retinitis pigmentosa (RP), protein misfolding leads to fatal consequences for cell metabolism and rod and cone cell survival. To stop disease progression, a therapeutic approach focuses on stabilizing inherited protein mutants of the G protein-coupled receptor (GPCR) rhodopsin using pharmacological chaperones (PC) that improve receptor folding and trafficking. In this study, we discovered stabilizing nonretinal small molecules by virtual and thermofluor screening and determined the crystal structure of pharmacologically stabilized opsin at 2...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Carlos G P Voogdt, Jaap A Wagenaar, Jos P M van Putten
Toll-like receptor 5 (TLR5) of mammals, birds, and reptiles detects bacterial flagellin and signals as a homodimeric complex. Structural studies using truncated TLR5b of zebrafish confirm the homodimeric TLR5-flagellin interaction. Here we provide evidence that zebrafish ( Danio rerio ) TLR5 unexpectedly signals as a heterodimer composed of the duplicated gene products drTLR5b and drTLR5a. Flagellin-induced signaling by the zebrafish TLR5 heterodimer increased in the presence of the TLR trafficking chaperone UNC93B1...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Martha A Zepeda-Rivera, Christina C Saak, Karine A Gibbs
The bacterium Proteus mirabilis can communicate identity through the secretion of the self-identity protein, IdsD, via the type VI secretion (T6S) system. IdsD secretion is essential for self versus non-self recognition behaviors in these populations. Here we provide an answer to the unresolved question of how the activity of a T6S substrate, such as IdsD, is regulated before secretion. We demonstrate that IdsD is found in clusters that form independently of the T6S machinery and activity. We show that the protein IdsC, which is a member of the proposed DUF4123 chaperone family, is essential for the maintenance of these clusters as well as the IdsD protein itself...
March 19, 2018: Journal of Bacteriology
Zimei Dong, Gengbo Chu, Yingxu Sima, Guangwen Chen
Heat shock protein 90 family members (HSP90s), as molecular chaperones, have conserved roles in the physiological processes of eukaryotes regulating cytoprotection, increasing host resistance and so on. However, whether HSP90s affect regeneration in animals is unclear. Planarians are emerging models for studying regeneration in vivo. Here, the roles of three hsp90 genes from planarian Dugesia japonica are investigated by WISH and RNAi. The results show that: (1) Djhsp90s expressions are induced by heat and cold shock, tissue damage and ionic liquid; (2) Djhsp90s mRNA are mainly distributed each side of the body in intact worms as well as blastemas in regenerative worms; (3) the worms show head regression, lysis, the body curling and the regeneration arrest or even failure after Djhsp90s RNAi; (4) Djhsp90s are involved in autophagy and locomotion of the body...
March 16, 2018: Biochemical and Biophysical Research Communications
Fazhao Li, Han Xiao, Zhiping Hu, Fangfang Zhou, Binbin Yang
HSPB8 is a member of ubiquitous small heat shock protein (sHSP) family, whose expression is induced in response to a wide variety of unfavorable physiological and environmental conditions. Investigation of HSPB8 structure indicated that HSPB8 belongs to the group of so-called intrinsically disordered proteins and possesses a highly flexible structure. Unlike most other sHSPs, HSPB8 tends to form small-molecular-mass oligomers and exhibits substrate-dependent chaperone activity. In cooperation with BAG3, the chaperone activity of HSPB8 was reported to be involved in the delivery of misfolded proteins to the autophagy machinery...
March 13, 2018: European Journal of Cell Biology
Anthony M Pedley, Georgios I Karras, Xin Zhang, Susan L Lindquist, Stephen J Benkovic
Despite purines being one of the largest classes of metabolites in a cell, little is known about the regulatory mechanisms that facilitate efficient purine production. Under conditions resulting in high purine demand, enzymes within the de novo purine biosynthetic pathway cluster into multi-enzyme assemblies called purinosomes. Purinosome formation has been linked to molecular chaperones HSP70 and HSP90; however, the involvement of these molecular chaperones in purinosome formation remains largely unknown. Here, we present a new found biochemical mechanism for the regulation of de novo purine biosynthetic enzymes mediated through HSP90...
March 19, 2018: Biochemistry
Dario Spigolon, D Travis Gallagher, Adrian Velazquez-Campoy, Donatella Bulone, Jatin Narang, Pier Luigi San Biagio, Francesco Cappello, Alberto J L Macario, Everly Conway de Macario, Frank T Robb
The human chaperonin complex is a ~ 1 MDa nanomachine composed of two octameric rings formed from eight similar but non-identical subunits called CCT. Here, we are elucidating the mechanism of a heritable CCT5 subunit mutation that causes profound neuropathy in humans. In previous work, we introduced an equivalent mutation in an archaeal chaperonin that assembles into two octameric rings like in humans but in which all subunits are identical. We reported that the hexadecamer formed by the mutant subunit is unstable with impaired chaperoning functions...
December 2017: Biochemistry and Biophysics Reports
Sailen Barik
The two classical immunophilin families, found essentially in all living cells, are: cyclophilin (CYN) and FK506-binding protein (FKBP). We previously reported a novel class of immunophilins that are natural chimera of these two, which we named dual-family immunophilin (DFI). The DFIs were found in either of two conformations: CYN-linker-FKBP (CFBP) or FKBP-3TPR-CYN (FCBP). While the 3TPR domain can serve as a flexible linker between the FKBP and CYN modules in the FCBP-type DFI, the linker sequences in the CFBP-type DFIs are relatively short, diverse in sequence, and contain no discernible motif or signature...
2018: Computational and Structural Biotechnology Journal
Chang Gao, Min Li, An-Li Jiang, Rui Sun, Hong-Lin Jin, Hua-Wei Gui, Fei Xiao, Xiang-Wu Ding, Zhen-Ming Fu, Jue-Ping Feng
Tumor necrosis factor receptor-associated protein-1 (TRAP-1), a mitochondrial chaperone, contributes significantly to the progression of cancer. However, the understanding of its involvement in the clinicopathological characteristics and prognosis of colorectal cancer (CRC) remains limited. The aim of the present study was to assess the significance of TRAP-1 expression in CRC. The expression of TRAP-1 was evaluated in corresponding cancerous, paracancerous, lymph node and distant metastatic tissues of 256 cases of CRC by immunohistochemistry...
April 2018: Oncology Letters
Yana Li, Shuna Sun, Zhiwen Ding, Chunjie Yang, Guoping Zhang, Qiu Jiang, Yunzeng Zou
Fibroblast growth factor binding proteins (FGFBPs) are a class of secreted proteoglycans that function as an extracellular chaperone for locally stored FGFs and enhance FGF signaling. To date, all three human FGFBP genes have been identified and one orthologue fgfbp1a has been studied in zebrafish embryos. Here, we described the cloning and expression patterns of four novel FGFBP orthologues in zebrafish, fgfbp1b, fgfbp2a, fgfbp2b, and fgfbp3. Quantitative PCR and whole-mount in situ hybridization results showed that all transcripts except fgfbp2a are initially expressed in a maternal manner...
March 15, 2018: Gene
Mikhail M Savitski, Nico Zinn, Maria Faelth-Savitski, Daniel Poeckel, Stephan Gade, Isabelle Becher, Marcel Muelbaier, Anne J Wagner, Katrin Strohmer, Thilo Werner, Stephanie Melchert, Massimo Petretich, Anna Rutkowska, Johanna Vappiani, Holger Franken, Michael Steidel, Gavain M Sweetman, Omer Gilan, Enid Y N Lam, Mark A Dawson, Rab K Prinjha, Paola Grandi, Giovanna Bergamini, Marcus Bantscheff
Protein degradation plays important roles in biological processes and is tightly regulated. Further, targeted proteolysis is an emerging research tool and therapeutic strategy. However, proteome-wide technologies to investigate the causes and consequences of protein degradation in biological systems are lacking. We developed "multiplexed proteome dynamics profiling" (mPDP), a mass-spectrometry-based approach combining dynamic-SILAC labeling with isobaric mass tagging for multiplexed analysis of protein degradation and synthesis...
March 3, 2018: Cell
C S Krumm, S L Giesy, C L Orndorff, Y R Boisclair
Adiponectin is an insulin-sensitizing hormone produced predominantly by adipose tissue; it circulates as oligomers of 3, 6, 18, or more units. Plasma adiponectin might be involved in the development of insulin resistance in transition dairy cows because it falls to a nadir around parturition. The possibility that this regulation occurs through a post-transcriptional mechanism was suggested in a previous study that showed unchanged adiponectin mRNA abundance combined with reduced expression of endoplasmic reticulum (ER) chaperones implicated in assembly of adiponectin oligomers...
March 14, 2018: Journal of Dairy Science
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