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https://www.readbyqxmd.com/read/28078859/role-of-vitacamphore-in-improving-central-pro-inflammatory-cytokines-following-transient-global-ischemia
#1
J Lin, L Pang, X L Liu, J Xing
Pro-inflammatory cytokines (PICs) including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are responsive to ischemic stress. This process thereby modulates the responsiveness of many cell types under diseased conditions. The current study was to examine the role played by vitacamphore (VCP) in regulating the levels of PICs and protein expression of PIC receptors in the cerebral cortex and hippocampus of rats after cardiac arrest (CA)-induced transient global ischemia. CA was induced by asphyxia followed by cardiopulmonary resuscitation (CPR) in rats...
October 2016: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28057298/amyotrophic-lateral-sclerosis-pathogenesis-converges-on-defects-in-protein-homeostasis-associated-with-tdp-43-mislocalization-and-proteasome-mediated-degradation-overload
#2
G Lin, D Mao, H J Bellen
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that affects upper and/or lower motor neurons. It usually affects people between the ages of 40-70. The average life expectancy is about 3-5 years after diagnosis and there is no effective cure available. Identification of variants in more than 20 different loci has provided insight into the pathogenic molecular mechanisms mediating disease pathogenesis. In this review, we focus on seven ALS-causing genes: TDP-43, FUS, C9orf72, VCP, UBQLN2, VAPB and SOD-1, which encompass about 90% of the variants causing familial ALS...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28051256/expression-of-serum-microrna-378-and-its-clinical-significance-in-laryngeal-squamous-cell-carcinoma
#3
Y Xu, Y-P Lin, D Yang, G Zhang, H-F Zhou
OBJECTIVE: Studies have demonstrated that miRNA -378 expressed in various malignant tumors. In the present study, we aim to explore the expression of serum miRNA-378 and its clinical significance in laryngeal squamous cell carcinoma (LSCC) patients. PATIENTS AND METHODS: A total of 127 LSCC patients, 127 vocal cord polyp (VCP) and 130 healthy controls were selected. RESULTS: The miRNA-378 level in LSCC and VCP group was significantly higher compared to healthy control, and LSCC group has the highest miRNA-378 level...
December 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28049840/cytosolic-fc-receptor-trim21-inhibits-seeded-tau-aggregation
#4
William A McEwan, Benjamin Falcon, Marina Vaysburd, Dean Clift, Adrian L Oblak, Bernardino Ghetti, Michel Goedert, Leo C James
Alzheimer's disease (AD) and other neurodegenerative disorders are associated with the cytoplasmic aggregation of microtubule-associated protein tau. Recent evidence supports transcellular transfer of tau misfolding (seeding) as the mechanism of spread within an affected brain, a process reminiscent of viral infection. However, whereas microbial pathogens can be recognized as nonself by immune receptors, misfolded protein assemblies evade detection, as they are host-derived. Here, we show that when misfolded tau assemblies enter the cell, they can be detected and neutralized via a danger response mediated by tau-associated antibodies and the cytosolic Fc receptor tripartite motif protein 21 (TRIM21)...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28036256/uv-induced-proteolysis-of-rna-polymerase-ii-is-mediated-by-vcp-p97-segregase-and-timely-orchestration-by-cockayne-syndrome-b-protein
#5
Jinshan He, Qianzheng Zhu, Gulzar Wani, Altaf A Wani
RNA polymerase II (RNAPII) acts as a damage sensor for transcription-coupled nucleotide excision repair (TC-NER) and undergoes proteolytic clearance from damaged chromatin by the ubiquitin-proteasome system (UPS). Here, we report that Valosin-containing protein (VCP)/p97, a druggable oncotarget, is essential for RNAPII's proteolytic clearance in mammalian cells. We show that inhibition of VCP/p97, or siRNA-mediated ablation of VCP/p97 and its cofactors UFD1 and UBXD7 severely impairs ultraviolet radiation (UVR)-induced RNAPII degradation...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28032027/valosin-containing-protein-is-a-target-of-5-l-fuligocandin%C3%A2-b-and-enhances-trail-resistance-in-cancer-cells
#6
Midori A Arai, Shota Taguchi, Kazuhiro Komatsuzaki, Kento Uchiyama, Ayaka Masuda, Mana Sampei, Mamoru Satoh, Sayaka Kado, Masami Ishibashi
Fuligocandin B (2) is a novel natural product that can overcome TRAIL resistance. We synthesized enatiomerically pure fuligocandin B (2) and its derivative 5'-I fuligocandin B (4), and found that the latter had an improved biological activity against the human gastric cancer cell line, AGS. We attached a biotin linker and photoactivatable aryl diazirine group to 5'-I fuligocandin B (4), and employed a pull-down assay to identify valosin-containing protein (VCP/p97), an AAA ATPase, as a 5'-I fuligocandin B (4) target protein...
December 2016: ChemistryOpen
https://www.readbyqxmd.com/read/27929047/caveolin-1-is-an-aggresome-inducing-protein
#7
Ajit Tiwari, Courtney A Copeland, Bing Han, Caroline A Hanson, Krishnan Raghunathan, Anne K Kenworthy
Caveolin-1 (Cav1) drives the formation of flask-shaped membrane invaginations known as caveolae that participate in signaling, clathrin-independent endocytosis and mechanotransduction. Overexpression or mutations of Cav1 can lead to its mistrafficking, including its accumulation in a perinuclear compartment previously identified as the Golgi complex. Here, we show that in the case of overexpressed Cav1-GFP, this perinuclear compartment consists of cytoplasmic inclusion bodies generated in response to the accumulation of aggregates of misfolded proteins, known as aggresomes...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27914931/valosin-containing-protein-vcp-p97-plays-a-role-in-the-replication-of-west-nile-virus
#8
Wallaya Phongphaew, Shintaro Kobayashi, Michihito Sasaki, Michael Carr, William W Hall, Yasuko Orba, Hirofumi Sawa
Valosin-containing protein (VCP) is classified as a member of the type II AAA(+) ATPase protein family. VCP functions in several cellular processes, including protein degradation, membrane fusion, vesicular trafficking and disassembly of stress granules. Moreover, VCP is considered to play a role in the replication of several viruses, albeit through different mechanisms. In the present study, we have investigated the role of VCP in West Nile virus (WNV) infection. Endogenous VCP expression was inhibited using either VCP inhibitors or by siRNA knockdown...
January 15, 2017: Virus Research
https://www.readbyqxmd.com/read/27913212/vcp-cooperates-with-ubxd1-to-degrade-mitochondrial-outer-membrane-protein-mcl1-in-model-of-huntington-s-disease
#9
Xing Guo, Xin Qi
Proteasome-dependent turnover of mitochondrial outer membrane (OMM)-associated proteins is one of the mechanisms for maintaining proper mitochondrial quality and function. However, the underlying pathways and their implications in human disease are poorly understood. Huntington's disease (HD) is a fatal, inherited neurodegenerative disorder caused by expanded CAG repeats in the N terminal of the huntingtin gene (mutant Huntingtin, mtHtt). In this study, we show an extensive degradation of the OMM protein MCL1 (Myeloid cell leukemia sequence 1) in both HD mouse striatal cells and HD patient fibroblasts...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27887991/vcp-p97-regulates-%C3%AE-2ar-quality-control-during-receptor-biosynthesis
#10
Richard Wargachuk, Irina Glazkova, Nicolas Audet, Darlaine Pétrin, Phan Trieu, Terence E Hébert
GPCRs form signalling complexes with other receptors as part of dimers, G proteins and effector partners. A proteomic screen to identify proteins that associate with the β2-adrenergic receptor (β2AR) identified many of components of the Endoplasmic-Reticulum-Associated Degradation (ERAD) quality control system [1], including the valosin-containing protein (VCP/p97). Here, we validated the interaction of VCP with co-expressed FLAG-β2AR, demonstrating, using an inducible expression system, that the interaction of FLAG-β2AR and VCP is not an artifact of overexpression of the β2AR per se...
January 2017: Cellular Signalling
https://www.readbyqxmd.com/read/27881037/a-novel-gel-pad-laryngeal-ultrasound-for-vocal-cord-evaluation
#11
Jung-Woo Woo, Seo Ki Kim, Inhye Park, Jun Ho Choe, Jung-Han Kim, Jee Soo Kim
BACKGROUND: Laryngeal ultrasound (LUS) is a new method for vocal cord evaluation in patients with risk of vocal cord palsy (VCP). However, the previously described LUS reportedly had a high failure rate of vocal cord visualization in male patients. A novel gel pad LUS was devised to overcome the limitations of the previous method. METHODS: A total of 482 (100 male) consecutive LUS and direct laryngoscopy examinations were performed in thyroidectomy and other neck surgery patients...
January 4, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/27861584/correction-ibmpfd-disease-causing-mutant-vcp-p97-proteins-are-targets-of-autophagic-lysosomal-degradation
#12
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0164864.].
2016: PloS One
https://www.readbyqxmd.com/read/27835930/master-autophagy-regulator-transcription-factor-eb-tfeb-regulates-cigarette-smoke-induced-autophagy-impairment-and-copd-emphysema-pathogenesis
#13
Manish Bodas, Neel Patel, David Silverberg, Kyla Walworth, Neeraj Vij
AIMS: Recent studies have shown that cigarette smoke (CS)-induced oxidative-stress impairs autophagy resulting in aggresome-formation that correlates with the severity of COPD-emphysema. Although, specific step in autophagy-pathway that is impaired is unknown. Hence, in this study we aimed to evaluate the role of master autophagy-regulator and transcription factor-EB (TFEB) in CS-induced COPD-emphysema pathogenesis. RESULTS: We first observed that TFEB-accumulates in the peri-nuclear spaces of the COPD lung tissues of tobacco-smokers and severe-emphysema subjects...
November 11, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27833496/unusual-cause-of-bilateral-vocal-cord-paralysis
#14
W M Hajjar, H A AlShalan, M A Alsowayyan, S A Al-Nassar
The most common cause of vocal cord paralysis (VCP) as a result of recurrent laryngeal nerve compression is malignant tumors. A benign and inflammatory causes of VCP is rarely reported in the literature, and in almost all reported cases it was a unilateral paralysis. We report a rare case of tuberculous mediastinal lymphadenopathy causing bilateral VCP in a young female patient.
October 2016: Saudi Journal of Anaesthesia
https://www.readbyqxmd.com/read/27828775/a-dynamic-molecular-basis-for-malfunction-in-disease-mutants-of-p97-vcp
#15
Anne K Schuetz, Lewis E Kay
p97/VCP is an essential, abundant AAA+ ATPase that is conserved throughout eukaryotes, with central functions in diverse processes ranging from protein degradation to DNA damage repair and membrane fusion. p97 has been implicated in the etiology of degenerative diseases and in cancer. Using Nuclear Magnetic Resonance spectroscopy we reveal how disease-causing mutations in p97 deregulate dynamics of the N-terminal domain that binds adaptor proteins involved in controlling p97 function. Our results provide a molecular basis for understanding how malfunction occurs whereby mutations shift the ADP-bound form of the enzyme towards an ATP-like state in a manner that correlates with disease severity...
November 9, 2016: ELife
https://www.readbyqxmd.com/read/27816355/correlations-between-serum-apolipoprotein-a-i-and-formation-of-vocal-cord-polyp
#16
Hui-Ping Zhang, Rong Zhang
OBJECTIVE: This study aims to investigate the correlations between serum apolipoprotein A-I (ApoA-I) and the formation of vocal cord polyps (VCPs). STUDY DESIGN: This study used the nonmatched case-control study method. METHODS: The serum total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, ApoA-I, apolipoprotein B (ApoB), and ApoA-I/ApoB levels of 89 VCP patients and 87 normal volunteers were compared...
November 2, 2016: Journal of Voice: Official Journal of the Voice Foundation
https://www.readbyqxmd.com/read/27768726/ibmpfd-disease-causing-mutant-vcp-p97-proteins-are-targets-of-autophagic-lysosomal-degradation
#17
Oznur Bayraktar, Ozlem Oral, Nur Mehpare Kocaturk, Yunus Akkoc, Karin Eberhart, Ali Kosar, Devrim Gozuacik
The ubiquitin-proteasome system (UPS) degrades soluble proteins and small aggregates, whereas macroautophagy (autophagy herein) eliminates larger protein aggregates, tangles and even whole organelles in a lysosome-dependent manner. VCP/p97 was implicated in both pathways. VCP/p97 mutations cause a rare multisystem disease called IBMPFD (Inclusion Body Myopathy with Paget's Disease and Frontotemporal Dementia). Here, we studied the role IBMPFD-related mutants of VCP/p97 in autophagy. In contrast with the wild-type VCP/p97 protein or R155C or R191Q mutants, the P137L mutant was aggregate-prone...
2016: PloS One
https://www.readbyqxmd.com/read/27762673/lessons-to-learn-after-1000-transcutaneous-laryngeal-ultrasound-tlusg-with-laryngoscopic-validation-is-there-a-role-of-tlusg-in-patients-indicated-for-laryngoscopic-examination-before-thyroidectomy
#18
Kai Pun Wong, Kin Pan Au, Shi Lam, Brian H Lang
INTRODUCTION: Patients with hoarseness of voice, previous neck operation or suspicion of malignancy are at "high-risk" of having pre-thyroidectomy vocal cord (VC) palsy. Therefore, VC functions should be evaluated before the operation. We aimed to evaluate the accuracy of hoarseness, voice related questionnaire (Voice handicap Index (VHI) - 30) and transcutaneous laryngeal ultrasound (TLUSG) in diagnosing VC palsy, as well as the role of TLUSG in the evaluation of high-risk patients. METHODS: 1000 patients undergoing thyroidectomy or other endocrine-related neck procedures were prospectively included...
October 20, 2016: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/27753622/vcp-p97-cooperates-with-yod1-ubxd1-and-plaa-to-drive-clearance-of-ruptured-lysosomes-by-autophagy
#19
Chrisovalantis Papadopoulos, Philipp Kirchner, Monika Bug, Daniel Grum, Lisa Koerver, Nina Schulze, Robert Poehler, Alina Dressler, Sven Fengler, Khalid Arhzaouy, Vanda Lux, Michael Ehrmann, Conrad C Weihl, Hemmo Meyer
Rupture of endosomes and lysosomes is a major cellular stress condition leading to cell death and degeneration. Here, we identified an essential role for the ubiquitin-directed AAA-ATPase, p97, in the clearance of damaged lysosomes by autophagy. Upon damage, p97 translocates to lysosomes and there cooperates with a distinct set of cofactors including UBXD1, PLAA, and the deubiquitinating enzyme YOD1, which we term ELDR components for Endo-Lysosomal Damage Response. Together, they act downstream of K63-linked ubiquitination and p62 recruitment, and selectively remove K48-linked ubiquitin conjugates from a subpopulation of damaged lysosomes to promote autophagosome formation...
October 17, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27735940/ddx3-dead-box-rna-helicase-plays-a-central-role-in-mitochondrial-protein-quality-control-in-leishmania
#20
Prasad Kottayil Padmanabhan, Ouafa Zghidi-Abouzid, Mukesh Samant, Carole Dumas, Bruno Guedes Aguiar, Jerome Estaquier, Barbara Papadopoulou
DDX3 is a highly conserved member of ATP-dependent DEAD-box RNA helicases with multiple functions in RNA metabolism and cellular signaling. Here, we describe a novel function for DDX3 in regulating the mitochondrial stress response in the parasitic protozoan Leishmania. We show that genetic inactivation of DDX3 leads to the accumulation of mitochondrial reactive oxygen species (ROS) associated with a defect in hydrogen peroxide detoxification. Upon stress, ROS production is greatly enhanced, causing mitochondrial membrane potential loss, mitochondrial fragmentation, and cell death...
October 13, 2016: Cell Death & Disease
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