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Unfolded Proteins

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https://www.readbyqxmd.com/read/28338903/disulfide-bridges-as-essential-elements-for-the-thermostability-of-lytic-polysaccharide-monooxygenase-lpmo10c-from-streptomyces-coelicolor
#1
Magali Tanghe, Barbara Danneels, Matthias Last, Koen Beerens, Ingeborg Stals, Tom Desmet
Lytic polysaccharide monooxygenases (LPMOs) are crucial components of cellulase mixtures but their stability has not yet been studied in detail, let alone been engineered for industrial applications. In this work, we have evaluated the importance of disulfide bridges for the thermodynamic stability of Streptomyces coelicolor LPMO10C. Interestingly, this enzyme was found to retain 34% of its activity after 2-h incubation at 80°C while its apparent melting temperature (Tm) is only 51°C. When its three disulfide bridges were broken, however, irreversible unfolding occurred and no residual activity could be detected after a similar heat treatment...
March 9, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28338097/the-cellular-protein-hnrnp-a2-b1-enhances-hiv-1-transcription-by-unfolding-ltr-promoter-g-quadruplexes
#2
Matteo Scalabrin, Ilaria Frasson, Emanuela Ruggiero, Rosalba Perrone, Elena Tosoni, Sara Lago, Martina Tassinari, Giorgio Palù, Sara N Richter
G-quadruplexes are four-stranded conformations of nucleic acids that act as cellular epigenetic regulators. A dynamic G-quadruplex forming region in the HIV-1 LTR promoter represses HIV-1 transcription when in the folded conformation. This activity is enhanced by nucleolin, which induces and stabilizes the HIV-1 LTR G-quadruplexes. In this work by a combined pull-down/mass spectrometry approach, we consistently found hnRNP A2/B1 as an additional LTR-G-quadruplex interacting protein. Surface plasmon resonance confirmed G-quadruplex specificity over linear sequences and fluorescence resonance energy transfer analysis indicated that hnRNP A2/B1 is able to efficiently unfold the LTR G-quadruplexes...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28338058/the-role-of-creb3l4-in-the-proliferation-of-prostate-cancer-cells
#3
Tae-Hyun Kim, Joo-Man Park, Mi-Young Kim, Yong-Ho Ahn
The incidence of prostate cancer (PC) is growing rapidly throughout the world, in probable association with the adoption of western style diets. Thus, understanding the molecular pathways triggering the development of PC is crucial for both its prevention and treatment. Here, we investigated the role of the metabolism-associated protein, CREB3L4, in the proliferation of PC cells. CREB3L4 was upregulated by the synthetic androgen, R1881, in LNCaP PC cells (an androgen-dependent cell line). Knockdown of CREB3L4 resulted in decreased androgen-dependent PC cell growth...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28337975/a-chemical-chaperone-improves-muscle-function-in-mice-with-a-ryr1-mutation
#4
Chang Seok Lee, Amy D Hanna, Hui Wang, Adan Dagnino-Acosta, Aditya D Joshi, Mark Knoblauch, Yan Xia, Dimitra K Georgiou, Jianjun Xu, Cheng Long, Hisayuki Amano, Corey Reynolds, Keke Dong, John C Martin, William R Lagor, George G Rodney, Ergun Sahin, Caroline Sewry, Susan L Hamilton
Mutations in the RYR1 gene cause severe myopathies. Mice with an I4895T mutation in the type 1 ryanodine receptor/Ca(2+) release channel (RyR1) display muscle weakness and atrophy, but the underlying mechanisms are unclear. Here we show that the I4895T mutation in RyR1 decreases the amplitude of the sarcoplasmic reticulum (SR) Ca(2+) transient, resting cytosolic Ca(2+) levels, muscle triadin content and calsequestrin (CSQ) localization to the junctional SR, and increases endoplasmic reticulum (ER) stress/unfolded protein response (UPR) and mitochondrial ROS production...
March 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28337301/endoplasmic-reticulum-stress-a-new-wrestler-in-the-pathogenesis-of-idiopathic-pulmonary-fibrosis
#5
Lei Zhang, Yi Wang, Nuruliarizki Shinta Pandupuspitasari, Guorao Wu, Xudong Xiang, Quan Gong, Weining Xiong, Cong-Yi Wang, Ping Yang, Boxu Ren
Idiopathic pulmonary fibrosis (IPF) has attracted extensive attention for its unexplained progressive lung scarring, short median survival and its unresponsiveness to traditional therapies. Despite extensive studies, the mechanisms underlying IPF pathoetiologies, however, remain poorly understood. Recent advances delineated a potential function of endoplasmic reticulum (ER) stress in meeting the need of fibrotic response, which pinpointed a critical role for the unfolded protein response (UPR) pathways in IPF pathogenesis...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28337298/xbp1-lox-axis-is-critical-in-er-stress-induced-growth-of-lung-adenocarcinoma-in-3d-culture
#6
Yi Yang, Bai-Jun Cheng, Hong Jian, Zhi-Wei Chen, Yi Zhao, Yong-Feng Yu, Zi-Ming Li, Mei-Lin Liao, Shun Lu
Rapid growth of tumor cells needs to consume large amounts of oxygen and glucose, due to lack of blood supply within the tumor, cells live in an environment that lack of oxygen and nutrients. This environment results in endoplasmic reticulum (ER) stress and activates the UPR (unfolded protein response). More and more evidence suggests UPR provides a growth signal pathway required for tumor growth. In the present study, we investigated the relationship between XBP1, one transcription factor in UPR, and the expression of LOX...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28337259/intranasal-basic-fibroblast-growth-factor-attenuates-endoplasmic-reticulum-stress-and-brain-injury-in-neonatal-hypoxic-ischaemic-injury
#7
Zhenlang Lin, Yingying Hu, Zhouguang Wang, Shulin Pan, Hao Zhang, Libing Ye, Hongyu Zhang, Mingchu Fang, Huai Jiang, Junming Ye, Jian Xiao, Li Liu
Brain injury secondary to birth asphyxia is the major cause of death and long-term disability in newborns. Intranasal drug administration enables agents to bypass the blood-brain barrier (BBB) and enter the brain directly. In this study, we determined whether intranasal basic fibroblast growth factor (bFGF) could exert neuroprotective effects in neonatal rats after hypoxic-ischaemic (HI) brain injury and assessed whether attenuation of endoplasmic reticulum (ER) stress was associated with these neuroprotective effects...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28336459/correlation-between-calculated-molecular-descriptors-of-excipient-amino-acids-and-experimentally-observed-thermal-stability-of-lysozyme
#8
Helena Meng-Lund, Natascha Friis, Marco van de Weert, Jukka Rantanen, Antti Poso, Holger Grohganz, Lene Jorgensen
A quantitative structure-property relationship (QSPR) between protein stability and the physicochemical properties of excipients was investigated to enable a more rational choice of stabilizing excipients than prior knowledge. The thermal transition temperature and aggregation time were determined for lysozyme in combination with 13 different amino acids using high throughput fluorescence spectroscopy and kinetic static light scattering measurements. On the theoretical side, around 200 2D and 3D molecular descriptors were calculated based on the amino acids' chemical structure...
March 20, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28335726/analysis-of-hepatic-transcript-profile-and-plasma-lipid-profile-in-early-lactating-dairy-cows-fed-grape-seed-and-grape-marc-meal-extract
#9
Denise K Gessner, Anne Winkler, Christian Koch, Georg Dusel, Gerhard Liebisch, Robert Ringseis, Klaus Eder
BACKGROUND: It was recently reported that dairy cows fed a polyphenol-rich grape seed and grape marc meal extract (GSGME) during the transition period had an increased milk yield, but the underlying reasons remained unclear. As polyphenols exert a broad spectrum of metabolic effects, we hypothesized that feeding of GSGME influences metabolic pathways in the liver which could account for the positive effects of GSGME in dairy cows. In order to identify these pathways, we performed genome-wide transcript profiling in the liver and lipid profiling in plasma of dairy cows fed GSGME during the transition period at 1 week postpartum...
March 23, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28335520/endoplasmic-reticulum-stress-and-unfolded-protein-response-in-cartilage-pathophysiology-contributing-factors-to-apoptosis-and-osteoarthritis
#10
REVIEW
Alexandria Hughes, Alexandra E Oxford, Ken Tawara, Cheryl L Jorcyk, Julia Thom Oxford
Chondrocytes of the growth plate undergo apoptosis during the process of endochondral ossification, as well as during the progression of osteoarthritis. Although the regulation of this process is not completely understood, alterations in the precisely orchestrated programmed cell death during development can have catastrophic results, as exemplified by several chondrodystrophies which are frequently accompanied by early onset osteoarthritis. Understanding the mechanisms that underlie chondrocyte apoptosis during endochondral ossification in the growth plate has the potential to impact the development of therapeutic applications for chondrodystrophies and associated early onset osteoarthritis...
March 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28334996/amelogenesis-imperfecta-caused-by-n-terminal-enamelin-point-mutations-in-mice-and-men-is-driven-by-endoplasmic-reticulum-stress
#11
Steven J Brookes, Martin J Barron, Claire E L Smith, James A Poulter, Alan J Mighell, Chris F Inglehearn, Catriona J Brown, Helen Rodd, Jennifer Kirkham, Michael J Dixon
"Amelogenesis imperfecta" (AI) describes a group of inherited diseases of dental enamel that have major clinical impact. Here, we identify the aetiology driving AI in mice carrying a p.S55I mutation in enamelin; one of the most commonly mutated proteins underlying AI in humans. Our data indicate that the mutation inhibits the ameloblast secretory pathway leading to ER stress and an activated unfolded protein response (UPR). Initially, with the support of the UPR acting in pro-survival mode, Enamp.S55I heterozygous mice secreted structurally normal enamel...
March 11, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334007/a-functional-variant-in-neph3-gene-confers-high-risk-of-renal-failure-in-primary-hematuric-glomerulopathies-evidence-for-predisposition-to-microalbuminuria-in-the-general-population
#12
Konstantinos Voskarides, Charalambos Stefanou, Myrtani Pieri, Panayiota Demosthenous, Kyriakos Felekkis, Maria Arsali, Yiannis Athanasiou, Dimitris Xydakis, Kostas Stylianou, Eugenios Daphnis, Giorgos Goulielmos, Petros Loizou, Judith Savige, Martin Höhne, Linus A Völker, Thomas Benzing, Patrick H Maxwell, Daniel P Gale, Mathias Gorski, Carsten Böger, Barbara Kollerits, Florian Kronenberg, Bernhard Paulweber, Michalis Zavros, Alkis Pierides, Constantinos Deltas
BACKGROUND: Recent data emphasize that thin basement membrane nephropathy (TBMN) should not be viewed as a form of benign familial hematuria since chronic renal failure (CRF) and even end-stage renal disease (ESRD), is a possible development for a subset of patients on long-term follow-up, through the onset of focal and segmental glomerulosclerosis (FSGS). We hypothesize that genetic modifiers may explain this variability of symptoms. METHODS: We looked in silico for potentially deleterious functional SNPs, using very strict criteria, in all the genes significantly expressed in the slit diaphragm (SD)...
2017: PloS One
https://www.readbyqxmd.com/read/28333839/evidence-for-increased-response-to-induced-endoplasmic-reticulum-stress-in-myeloid-cells-in-acquired-aplastic-anemia
#13
Alpa Sidhu, Michael U Callaghan, Manisha S Gadgeel, Steven A Buck, Andrew M Fribley, Süreyya Savaşan
Autoimmune response targeting the hematopoietic stem cells highlights the current understanding of acquired aplastic anemia (AAA) pathogenesis. Upregulation of the unfolded protein response is the cell's rejoinder to a variety of stresses, which either result in restoring homeostasis or cell death by increased expression of the transcription factor C/EBP homologous protein. We hypothesized that there is an inherent increased sensitivity to various cellular stressors, including the ones that target endoplasmic reticulum (ER) in AAA leading to a decreased proliferation and potentially contributing to susceptibility to autologous cytotoxicity...
April 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28333162/the-endoplasmic-reticulum-chaperone-grp78-bip-modulates-prion-propagation-in-vitro-and-in-vivo
#14
Kyung-Won Park, Gyoung Eun Kim, Rodrigo Morales, Fabio Moda, Ines Moreno-Gonzalez, Luis Concha-Marambio, Amy S Lee, Claudio Hetz, Claudio Soto
Prion diseases are fatal neurodegenerative disorders affecting several mammalian species, characterized by the accumulation of the misfolded form of the prion protein, which is followed by the induction of endoplasmic reticulum (ER) stress and the activation of the unfolded protein response (UPR). GRP78, also called BiP, is a master regulator of the UPR, reducing ER stress levels and apoptosis due to an enhancement of the cellular folding capacity. Here, we studied the role of GRP78 in prion diseases using several in vivo and in vitro approaches...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332979/the-perk-arm-of-the-unfolded-protein-response-regulates-satellite-cell-mediated-skeletal-muscle-regeneration
#15
Guangyan Xiong, Sajedah M Hindi, Aman K Mann, Yann Simon Gallot, Kyle R Bohnert, Douglas R Cavener, Scott R Whittemore, Ashok Kumar
Regeneration of skeletal muscle in adults is mediated by satellite stem cells. Accumulation of misfolded proteins triggers endoplasmic reticulum stress that leads to unfolded protein response (UPR). The UPR is relayed to the cell through the activation of PERK, IRE1/XBP1, and ATF6. Here, we demonstrate that levels of PERK and IRE1 are increased in satellite cells upon muscle injury. Inhibition of PERK, but not the IRE1 arm of the UPR in satellite cells inhibits myofiber regeneration in adult mice. PERK is essential for the survival and differentiation of activated satellite cells into the myogenic lineage...
March 23, 2017: ELife
https://www.readbyqxmd.com/read/28331281/the-involvement-of-atf4-and-s-opsin-in-retinal-photoreceptor-cell-damage-induced-by-blue-led-light
#16
Emi Ooe, Kazuhiro Tsuruma, Yoshiki Kuse, Saori Kobayashi, Masamitsu Shimazawa, Hideaki Hara
PURPOSE: Blue light is a high-energy emitting light with a short wavelength in the visible light spectrum. Blue light induces photoreceptor apoptosis and causes age-related macular degeneration or retinitis pigmentosa. In the present study, we investigated the roles of endoplasmic reticulum (ER) stress induced by blue light-emitting diode (LED) light exposure in murine photoreceptor cells. METHODS: The murine photoreceptor cell line was incubated and exposed to blue LED light (464 nm blue LED light, 450 lx, 3 to 24 h)...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28330852/a-controlled-release-mitochondrial-protonophore-reverses-hypertriglyceridemia-nonalcoholic-steatohepatitis-and-diabetes-in-lipodystrophic-mice
#17
Abudukadier Abulizi, Rachel J Perry, João Paulo G Camporez, Michael J Jurczak, Kitt Falk Petersen, Patricia Aspichueta, Gerald I Shulman
Lipodystrophy is a rare disorder characterized by complete or partial loss of adipose tissue. Patients with lipodystrophy exhibit hypertriglyceridemia, severe insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis (NASH). Efforts to ameliorate NASH in lipodystrophies with pharmacologic agents have met with limited success. We examined whether a controlled-release mitochondrial protonophore (CRMP) that produces mild liver-targeted mitochondrial uncoupling could decrease hypertriglyceridemia and reverse NASH and diabetes in a mouse model (fatless AZIP/F-1 mice) of severe lipodystrophy and diabetes...
March 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28330496/calcium-dysregulation-functional-calpainopathy-and-endoplasmic-reticulum-stress-in-sporadic-inclusion-body-myositis
#18
David R Amici, Iago Pinal-Fernandez, Davi A G Mázala, Thomas E Lloyd, Andrea M Corse, Lisa Christopher-Stine, Andrew L Mammen, Eva R Chin
Sporadic inclusion body myositis (IBM) is the most common primary myopathy in the elderly, but its pathoetiology is still unclear. Perturbed myocellular calcium (Ca(2+)) homeostasis can exacerbate many of the factors proposed to mediate muscle degeneration in IBM, such as mitochondrial dysfunction, protein aggregation, and endoplasmic reticulum stress. Ca(2+) dysregulation may plausibly be initiated in IBM by immune-mediated membrane damage and/or abnormally accumulating proteins, but no studies to date have investigated Ca(2+) regulation in IBM patients...
March 22, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28330421/the-proteinopathy-of-d169g-and-k263e-mutants-at-the-rna-recognition-motif-rrm-domain-of-tar-dna-binding-protein-tdp43-causing-neurological-disorders-a-computational-study
#19
Vishwambhar Vishnu Bhandare, Amutha Ramaswamy
One of the multitasking proteins, transactive response DNA-binding protein 43 (tdp43) plays a key role in RNA regulation and the two pathogenic mutations such as D169G and K263E, located at the RNA Recognition Motif (RRM) of tdp43, are reported to cause neurological disorders such as Amyotrophic Lateral Sclerosis (ALS) and Fronto Temporal Lobar Degeneration (FTLD). As the exploration of the proteinopathy demands both structural and functional characterization of mutants, a comparative analysis on the wild type and mutant tdp43 (D169G and K263E) and their complexes with RNA have been performed using computational approaches...
March 22, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28329421/naproxen-inhibits-uvb-induced-basal-cell-and-squamous-cell-carcinoma-development-in-ptch1-skh-1-hairless-mice
#20
Sandeep C Chaudhary, Mohammad Waseem, Mehtab Rana, Hui Xu, Levy Kopelovich, Craig A Elmets, Mohammad Athar
Naproxen possesses anti-proliferative and pro-apoptotic effects besides its known anti-inflammatory functions. Here, we demonstrate the anti-cancer effects of naproxen against UVB-induced BCCs and SCCs in a highly susceptible murine model of UVB carcinogenesis. Naproxen significantly inhibited UVB-induced BCCs and SCCs in this model. Tumor number and volume were significantly decreased (p<0.005 and p<0.05, respectively). Inhibition in UVB-induced SCCs and BCCs was 77% and 86%, respectively, which was associated with reduced PCNA and cyclin D1 and increased apoptosis...
March 22, 2017: Photochemistry and Photobiology
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