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Nilisha Fernando, Riccardo Natoli, Tanja Racic, Yvette Wooff, Jan Provis, Krisztina Valter
The complement system is highly implicated in both the prevalence and progression of Age-Related Macular Degeneration (AMD). Complement system inhibitors therefore have potential therapeutic value in managing excessive activation of the complement pathways in retinal degenerations. The vaccinia virus complement control protein (VCP) has been shown to be effective as a complement inhibitor in neuroinflammatory models including traumatic brain injury and spinal cord injury. We aimed to investigate the potential of VCP as a therapeutic molecule for retinal degenerations...
2018: PloS One
Yukie Kushimura, Takahiko Tokuda, Yumiko Azuma, Itaru Yamamoto, Ikuko Mizuta, Toshiki Mizuno, Masanori Nakagawa, Morio Ueyama, Yoshitaka Nagai, Hideki Yoshida, Masamitsu Yamaguchi
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterized by the motor neuron degeneration that eventually leads to complete paralysis and death within 2-5 years after disease onset. One of the major pathological hallmark of ALS is abnormal accumulation of inclusions containing TAR DNA-binding protein-43 (TDP-43). TDP-43 is normally found in the nucleus, but in ALS, it localizes in the cytoplasm as inclusions as well as in the nucleus. Loss of nuclear TDP-43 functions likely contributes to neurodegeneration...
2018: American Journal of Neurodegenerative Disease
B Lan, S Chai, P Wang, K Wang
VCP/p97/Cdc48, a member of the ATPases associated with diverse cellular activities (AAA) family, is necessary for the endoplasmic-reticulum-associated protein degradation (ERAD) pathway to maintain protein homeostasis. Overwhelming proteotoxic stress drove cancer cells to enhance VCP/p97/Cdc48-associated ERAD to maintain protein homeostasis for survival, demonstrating that VCP/p97/Cdc48 expression was positively correlated with cancer prognosis. More studies revealed that targeting VCP/p97/Cdc48 could be a potential target in cancer therapy...
March 7, 2018: Current Molecular Medicine
Edmond Y Huang, Milton To, Erica Tran, Lorraine T Ador Dionisio, Hyejin J Cho, Katherine L M Baney, Camille I Pataki, James A Olzmann
Endoplasmic reticulum (ER)-associated degradation (ERAD) mediates the proteasomal clearance of proteins from the early secretory pathway. In this process, ubiquitinated substrates are extracted from membrane-embedded dislocation complexes by the AAA ATPase VCP and targeted to the cytosolic 26S proteasome. In addition to its well-established role in the degradation of misfolded proteins, ERAD also regulates the abundance of key proteins such as enzymes involved in cholesterol synthesis. However, due to the lack of generalizable methods, our understanding of the scope of proteins targeted by ERAD remains limited...
March 7, 2018: Molecular Biology of the Cell
Melissa G Y Lee, Johnny Millar, Elizabeth Rose, Aleesha Jones, Dora Wood, Taryn L Luitingh, Diana Zannino, Johann Brink, Igor E Konstantinov, Christian P Brizard, Yves d'Udekem
OBJECTIVES: To determine the incidence of vocal cord paresis (VCP) after neonatal aortic arch repair/Norwood-type procedure, and the effectiveness of noninvasive laryngeal ultrasound in detecting VCP compared with gold standard invasive nasoendoscopy. METHODS: Fifty-two patients who underwent an arch repair (39 of 52; 75%) or Norwood-type procedure (13 of 52; 25%) via sternotomy between April 1, 2015, and April 30, 2017 underwent laryngeal ultrasound (50 of 52; 96%) and/or flexible fiber optic nasoendoscopy (39 of 52; 75%) at 48 to 72 hours after endotracheal extubation...
February 9, 2018: Journal of Thoracic and Cardiovascular Surgery
Tatiana Sofía Rodriguez-Reyna, Chiara Bertolazzi, Angélica Vargas-Guerrero, Marwin Gutiérrez, Gabriela Hernández-Molina, Marcelo Audisio, Susana Roverano, Margarita González de Urizar, José Francisco Díaz Coto, Blanca Elizabeth Herrera Velasco, Mijahil Pavel Cornejo Ortega, Ana María Sapag Durán, Janeth Edelina Villegas Guzmán, Luís Fernando Medina Quintero, Mirtha Sabelli, Sandy Sapag Durán, Maurizio Cutolo
Nailfold videocapillaroscopy (VCP) allows non-invasive assessment of the microcirculation. Adequate training in this field is relevant for rheumatologists. There is increasing evidence of the reliability of VCP findings among different readers. OBJECTIVE: To evaluate inter- and intra-reader agreement of rheumatologists to identify normal images and systemic sclerosis (SSc) patterns on VCP ("early," "active," and "late" proposed by Cutolo et al.). Thirteen rheumatologists with different experience in nailfold VCP received training to standardize reading criteria...
February 23, 2018: Clinical Rheumatology
Jan B Heidelberger, Andrea Voigt, Marina E Borisova, Giuseppe Petrosino, Stefanie Ruf, Sebastian A Wagner, Petra Beli
Valosin-containing protein (VCP) is an evolutionarily conserved ubiquitin-dependent ATPase that mediates the degradation of proteins through the ubiquitin-proteasome pathway. Despite the central role of VCP in the regulation of protein homeostasis, identity and nature of its cellular substrates remain poorly defined. Here, we combined chemical inhibition of VCP and quantitative ubiquitin remnant profiling to assess the effect of VCP inhibition on the ubiquitin-modified proteome and to probe the substrate spectrum of VCP in human cells...
February 21, 2018: EMBO Reports
Anke Hüls, Andrea Vierkötter, Dorothea Sugiri, Michael J Abramson, Ulrich Ranft, Ursula Krämer, Tamara Schikowski
Air pollution has been associated with impaired lung and cognitive function, especially impairment in visuo-construction performance (VCP). In this article, we evaluate whether the effect of air pollution on VCP is mediated by lung function.We used data from the SALIA cohort (baseline 1985-1994 and follow-up 2007-2010) including 587 women aged 55 years at baseline. Particulate matter (PM) and nitrogen dioxide (NO2 ) exposures at baseline were estimated via land-use regression models. Lung function was characterised by averages between baseline and follow-up...
February 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Yogitha Thattikota, Sylvain Tollis, Roger Palou, Justine Vinet, Mike Tyers, Damien D'Amours
The morphological transformation of amorphous chromatin into distinct chromosomes is a hallmark of mitosis. To achieve this, chromatin must be compacted and remodeled by a ring-shaped enzyme complex known as condensin. However, the mechanistic basis underpinning condensin's role in chromosome remodeling has remained elusive. Here we show that condensin has a strong tendency to trap itself in its own reaction product during chromatin compaction and yet is capable of interacting with chromatin in a highly dynamic manner in vivo...
February 15, 2018: Molecular Cell
Brian C McDonald, Joost A de Gouw, Jessica B Gilman, Shantanu H Jathar, Ali Akherati, Christopher D Cappa, Jose L Jimenez, Julia Lee-Taylor, Patrick L Hayes, Stuart A McKeen, Yu Yan Cui, Si-Wan Kim, Drew R Gentner, Gabriel Isaacman-VanWertz, Allen H Goldstein, Robert A Harley, Gregory J Frost, James M Roberts, Thomas B Ryerson, Michael Trainer
A gap in emission inventories of urban volatile organic compound (VOC) sources, which contribute to regional ozone and aerosol burdens, has increased as transportation emissions in the United States and Europe have declined rapidly. A detailed mass balance demonstrates that the use of volatile chemical products (VCPs)-including pesticides, coatings, printing inks, adhesives, cleaning agents, and personal care products-now constitutes half of fossil fuel VOC emissions in industrialized cities. The high fraction of VCP emissions is consistent with observed urban outdoor and indoor air measurements...
February 16, 2018: Science
Pim Knuiman, Maria T E Hopman, Jeroen A Wouters, Marco Mensink
Background: Substantial research has been done on the impact of carbohydrate and fat availability on endurance exercise adaptation, though its role in the acute adaptive response to resistance exercise has yet to be fully characterized. Purpose: We aimed to assess the effects of a pre-resistance exercise isocaloric mixed meal containing different amounts of carbohydrates and fat, on post-resistance exercise gene expression associated with muscle adaptation. Methods: Thirteen young (age 21.2 ± 1.6 year), recreationally trained (VO2max 51...
2018: Frontiers in Physiology
Tiffany Marcantonio, D J Angelone, Meredith Joppa
OBJECTIVE: Verbal coercion (VC) is a common sexual assault tactic whereby men and women can be victims or perpetrators. College study abroad students report engagement in casual sex, alcohol consumption, and immersion in a sexualized environment (e.g., an environment that supports or encourages sexual activity); factors highly associated with sexual assault in general. The purpose of this study was to examine casual sex, alcohol use, and sexualized environments with VC victimization (VCV) and perpetration (VCP) while abroad...
February 6, 2018: Journal of American College Health: J of ACH
Emily Bergbower, Clement Boinot, Inna Sabirzhanova, William Guggino, Liudmila Cebotaru
BACKGROUND/AIMS: The CFTR-Associated Ligand (CAL), a PDZ domain containing protein with two coiled-coil domains, reduces cell surface WT CFTR through degradation in the lysosome by a well-characterized mechanism. However, CAL's regulatory effect on ΔF508 CFTR has remained almost entirely uninvestigated. METHODS: In this study, we describe a previously unknown pathway for CAL by which it regulates the membrane expression of ΔF508 CFTR through arrest of ΔF508 CFTR trafficking in the endoplasmic reticulum (ER) using a combination of cell biology, biochemistry and electrophysiology...
January 29, 2018: Cellular Physiology and Biochemistry
Kathrin Glaeser, Manuela Urban, Emma Fenech, Oksana Voloshanenko, Dominique Kranz, Federica Lari, John C Christianson, Michael Boutros
Active regulation of protein abundance is an essential strategy to modulate cellular signaling pathways. Within the Wnt signaling cascade, regulated degradation of β-catenin by the ubiquitin-proteasome system (UPS) affects the outcome of canonical Wnt signaling. Here, we found that abundance of the Wnt cargo receptor Evi (Wls/GPR177), which is required for Wnt protein secretion, is also regulated by the UPS through endoplasmic reticulum (ER)-associated degradation (ERAD). In the absence of Wnt ligands, Evi is ubiquitinated and targeted for ERAD in a VCP-dependent manner...
January 29, 2018: EMBO Journal
Bruna Figueiredo Costa, Patrizia Cassella, Sara Francesca Colombo, Nica Borgese
Tail-anchored (TA) proteins insert into their target organelles by incompletely elucidated post-translational pathways. Some TA proteins spontaneously insert into protein-free liposomes, yet target a specific organelle in vivo. Two spontaneously inserting cytochrome b5 forms, b5-ER and b5-RR, which differ only in the charge of the C-terminal region, target the ER or the mitochondrial outer membrane (MOM), respectively. To bridge the gap between the cell-free and in cellula results, we analyzed targeting in digitonin-permeabilized adherent HeLa cells...
January 23, 2018: Traffic
Prabhakar Bastola, Jeremy Chien
No abstract text is available yet for this article.
January 18, 2018: Cell Death & Disease
Mohammad A M Ali, Hilmar Strickfaden, Brian L Lee, Leo Spyracopoulos, Michael J Hendzel
Ring1-YY1-binding protein (RYBP) is a member of the non-canonical polycomb repressive complex 1 (PRC1), and like other PRC1 members, it is best described as a transcriptional regulator. However, several PRC1 members were recently shown to function in DNA repair. Here, we report that RYBP preferentially binds K63-ubiquitin chains via its Npl4 zinc finger (NZF) domain. Since K63-linked ubiquitin chains are assembled at DNA double-strand breaks (DSBs), we examined the contribution of RYBP to DSB repair. Surprisingly, we find that RYBP is K48 polyubiquitylated by RNF8 and rapidly removed from chromatin upon DNA damage by the VCP/p97 segregase...
January 9, 2018: Cell Reports
A Gareau, C Rico, D Boerboom, M-E Nadeau
Valosin-containing protein (VCP), through its critical role in the maintenance of protein homeostasis, is a promising target for the treatment of several malignancies, including canine lymphoma. CB-5083, a first-in-class VCP inhibitor, exerts cytotoxicity through the induction of irreversible proteotoxic stress and possesses a broad spectrum of anticancer activity. Here, we determined the cytotoxicity CB-5083 in canine lymphoma cells and its mechanism of action in vitro. Canine lymphoma cell lines were treated with varying concentrations of CB-5083 and assessed for viability by trypan blue exclusion and apoptosis by caspase activity assays...
January 4, 2018: Veterinary and Comparative Oncology
Yu-Tzu Shih, Yi-Ping Hsueh
The endoplasmic reticulum (ER) is the biggest organelle in cells and is involved in versatile cellular processes. Formation and maintenance of ER morphology are regulated by a series of proteins controlling membrane fusion and curvature. At least six different ER morphology regulators have been demonstrated to be involved in neurological disorders-including Valosin-containing protein (VCP), Atlastin-1 (ATL1), Spastin (SPAST), Reticulon 2 (RTN2), Receptor expression enhancing protein 1 (REEP1) and RAB10-suggesting a critical role of ER formation in neuronal activity and function...
January 8, 2018: Journal of Biomedical Science
Ning Zhou, Shaunrick Stoll, Hongyu Qiu
No abstract text is available yet for this article.
December 26, 2017: Aging
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