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https://www.readbyqxmd.com/read/28539497/correction-to-extracellular-cyclophilin-a-especially-acetylated-causes-pulmonary-hypertension-by-stimulating-endothelial-apoptosis-redox-stress-and-inflammation
#1
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No abstract text is available yet for this article.
June 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28535337/overall-structural-model-of-ns5a-protein-from-hepatitis-c-virus-and-modulation-by-mutations-confering-resistance-of-virus-replication-to-cyclosporin-a
#2
Aurelie Badillo, Veronique Brechot, Stephane Sarrazin, François-Xavier Cantrelle, Frederic Delolme, Marie-Laure Fogeron, Jennifer Molle, Roland Montserret, Anja Bockmann, Ralf Bartenschlager, Volker Lohmann, Guy Lippens, Sylvie Ricard-Blum, Xavier Hanoulle, Francois Penin
Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a RNA-binding phosphoprotein composed of a N-terminal membrane anchor (AH), a structured domain 1 (D1) and two intrinsically disordered domains (D2 and D3). The knowledge of the functional architecture of this multifunctional protein remains limited. We report here that NS5A-D1D2D3 produced in a wheat germ cell-free system is obtained under a highly phosphorylated state. Its NMR analysis revealed that these phosphorylations do not change the disordered nature of D2 and D3 domains but increase the number of conformers due to partial phosphorylations...
May 23, 2017: Biochemistry
https://www.readbyqxmd.com/read/28518150/cycloheximide-promotes-paraptosis-induced-by-inhibition-of-cyclophilins-in-glioblastoma-multiforme
#3
Lin Wang, Justin H Gundelach, Richard J Bram
Cancer is the second leading cause of death worldwide. Current treatment strategies based on multi-agent chemotherapy and/or radiation regimens have improved overall survival in some cases. However, resistance to apoptosis often develops in cancer cells, and its occurrence is thought to contribute to treatment failure. Non-apoptotic cell death mechanisms have become of great interest, therefore, in hopes that they would bypass tumor cell resistance. Glioblastoma multiforme (GBM), a grade IV astrocytic tumor is the most frequent brain tumor in adults, and has a high rate of mortality...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28506462/a-slow-conformational-switch-in-the-bmal1-transactivation-domain-modulates-circadian-rhythms
#4
Chelsea L Gustafson, Nicole C Parsley, Hande Asimgil, Hsiau-Wei Lee, Christopher Ahlbach, Alicia K Michael, Haiyan Xu, Owen L Williams, Tara L Davis, Andrew C Liu, Carrie L Partch
The C-terminal transactivation domain (TAD) of BMAL1 (brain and muscle ARNT-like 1) is a regulatory hub for transcriptional coactivators and repressors that compete for binding and, consequently, contributes to period determination of the mammalian circadian clock. Here, we report the discovery of two distinct conformational states that slowly exchange within the dynamic TAD to control timing. This binary switch results from cis/trans isomerization about a highly conserved Trp-Pro imide bond in a region of the TAD that is required for normal circadian timekeeping...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28501872/a-mechanism-study-underlying-the-protective-effects-of-cyclosporine-a-on-lung-ischemia-reperfusion-injury
#5
Jian''an Li, Zhongya Yan, Qianjin Fang
AIM: This study is aimed at validating the hypothesis that administration of cyclosporine-A (CsA) would be protective in lung ischemia-reperfusion (I/R) injury and in exploring the underlying mechanism. METHODS: Rabbits were divided into 4 groups: the control, sham operation, I/R, and I/R with CsA treatment. Flow cytometry was used to measure the mitochondrial membrane potential. Laser scanning confocal microscope was used to analyze mitochondrion permeability transition pore (MPTP)...
May 10, 2017: Pharmacology
https://www.readbyqxmd.com/read/28492973/fast-therapeutic-hypothermia-prevents-post-cardiac-arrest-syndrome-through-cyclophilin-d-mediated-mitochondrial-permeability-transition-inhibition
#6
Vincent Jahandiez, Martin Cour, Thomas Bochaton, Maryline Abrial, Joseph Loufouat, Abdallah Gharib, Annie Varennes, Michel Ovize, Laurent Argaud
The opening of the mitochondrial permeability transition pore (PTP), which is regulated by the matrix protein cyclophilin D (CypD), plays a key role in the pathophysiology of post-cardiac arrest (CA) syndrome. We hypothesized that therapeutic hypothermia could prevent post-CA syndrome through a CypD-mediated PTP inhibition in both heart and brain. In addition, we investigated whether specific pharmacological PTP inhibition would confer additive protection to cooling. Adult male New Zealand White rabbits underwent 15 min of CA followed by 120 min of reperfusion...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28487964/effects-of-the-cyclophilin-type-peptidylprolyl-cis-trans-isomerase-from-pyropia-yezoensis-against-hydrogen-peroxide-induced-oxidative-stress-in-hepg2-cells
#7
Eun-Young Kim, Youn Hee Choi, Chang Geun Choi, Taek-Jeong Nam
The present study aimed to describe the expression and purification of cyclophilin-type peptidylprolyl cis-trans isomerase (PPI) from the red alga Pyropia yezoensis. The antioxidant activity of the purified protein was also demonstrated, based on its ability to act against oxidative stress in HepG2 human hepatocellular carcinoma cells. HepG2 cells that were treated with recombinant PPI protein exhibited a reduction in the formation of hydrogen peroxide (H2O2)‑mediated reactive oxygen species (ROS). In HepG2 cells, treatment of recombinant PPI protein expression diminished H2O2‑mediated oxidative stress and restored both the expression and the activity of certain antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and thioredoxin reductase (TRR)...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28479159/proteomic-analysis-of-filaggrin-deficiency-identifies-molecular-signatures-characteristic-of-atopic-eczema
#8
Martina S Elias, Heather A Long, Carla F Newman, Paul A Wilson, Andrew West, Paul J McGill, Keith C Wu, Michael J Donaldson, Nick J Reynolds
BACKGROUND: Atopic eczema (AE) is characterized by skin barrier and immune dysfunction. Null mutations in filaggrin (FLG), a key epidermal barrier protein, strongly predispose to AE; however, the precise role of FLG deficiency in AE pathogenesis remains incompletely understood. OBJECTIVES: We sought to identify global proteomic changes downstream of FLG deficiency in human epidermal living skin-equivalent (LSE) models and validate findings in skin of patients with AE...
April 28, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28473712/bioinformatic-and-expression-analysis-of-the-brassica-napus-l-cyclophilins
#9
Patrizia Hanhart, Melanie Thieß, Khalid Amari, Krzysztof Bajdzienko, Patrick Giavalisco, Manfred Heinlein, Julia Kehr
Cyclophilins (CYPs) are a group of ubiquitous proteins characterized by their ability to bind to the immunosuppressive drug cyclosporin A. The CYP family occurs in a wide range of organisms and contains a conserved peptidyl-prolyl cis/trans isomerase domain. In addition to fulfilling a basic role in protein folding, CYPs may also play diverse important roles, e.g. in protein degradation, mRNA processing, development, and stress responses. We performed a genome-wide database survey and identified a total of 94 CYP genes encoding 91 distinct proteins...
May 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28454299/rna-interference-mediated-gene-silencing-of-cyclophilin-a-enhances-the-radiosensitivity-of-paa-human-lung-adenocarcinoma-cells-in-vitro
#10
Xin Jiang, Qiao-Li Zhang, Ye-Hong Tian, Jin-Chang Huang, Guo-Lin Ma
Radiotherapy is currently the major therapeutic strategy for patients with lung cancer. However, radioresistance and various side effects continue to present challenging issues for this form of treatment. A recent study demonstrated that cyclophilin A (CyPA) was overexpressed in non-small cell lung cancer and, therefore, presents a novel potential therapeutic target. In addition, gene-radiotherapy is a novel method for cancer treatment. Therefore, the objective of the present study was to investigate the potential effect of CyPA silencing on radiosensitivity in human lung adenocarcinoma in vitro...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28450293/extracellular-cyclophilin-a-especially-acetylated-causes-pulmonary-hypertension-by-stimulating-endothelial-apoptosis-redox-stress-and-inflammation
#11
Chao Xue, Mark Sowden, Bradford C Berk
OBJECTIVE: Oxidative stress and inflammation play key roles in the development of pulmonary arterial hypertension (PAH). Cyclophilin A (CypA) is secreted in response to oxidative stress and promotes inflammation and cardiovascular disease. Endothelial cell (EC) dysfunction is an early event in the pathogenesis of PAH. We evaluated the role of extracellular CypA in PAH and compared the effects of acetylated CypA (AcK-CypA, increased by oxidative stress) and CypA on EC dysfunction. APPROACH AND RESULTS: In transgenic mice that express high levels of CypA in EC specifically, a PAH phenotype was observed at 3 months including increased right ventricular systolic pressure, α-smooth muscle actin expression in small arterioles, and CD45-positive cells in the lungs...
April 27, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28450114/the-novel-cyclophilin-d-inhibitor-compound-19-protects-retinal-pigment-epithelium-cells-and-retinal-ganglion-cells-from-uv-radiation
#12
Laiqing Xie, Long Cheng, Guoxu Xu, Ji Zhang, Xiaoyan Ji, E Song
Excessive Ultra violet (UV) radiation induces injuries to retinal pigment epithelium (RPE) cells (RPEs) and retinal ganglion cells (RGCs), causing retinal degeneration. Cyclophilin D (Cyp-D)-dependent mitochondrial permeability transition pore (mPTP) opening mediates UV-induced cell death. In this study, we show that a novel Cyp-D inhibitor compound 19 efficiently protected RPEs and RGCs from UV radiation. Compound 19-mediated cytoprotection requires Cyp-D, as it failed to further protect RPEs/RGCs from UV when Cyp-D was silenced by targeted shRNAs...
June 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28442737/structural-and-biochemical-insights-of-cypa-and-aif-interaction
#13
Biancamaria Farina, Gianluigi Di Sorbo, Angela Chambery, Andrea Caporale, Guido Leoni, Rosita Russo, Fabiola Mascanzoni, Domenico Raimondo, Roberto Fattorusso, Menotti Ruvo, Nunzianna Doti
The Cyclophilin A (CypA)/Apoptosis Inducing Factor (AIF) complex is implicated in the DNA degradation in response to various cellular stress conditions, such as oxidative stress, cerebral hypoxia-ischemia and traumatic brain injury. The pro-apoptotic form of AIF (AIF(Δ1-121)) mainly interacts with CypA through the amino acid region 370-394. The AIF(370-394) synthetic peptide inhibits complex formation in vitro by binding to CypA and exerts neuroprotection in a model of glutamate-mediated oxidative stress. Here, the binding site of AIF(Δ1-121) and AIF(370-394) on CypA has been mapped by NMR spectroscopy and biochemical studies, and a molecular model of the complex has been proposed...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428752/desensitizing-mitochondrial-permeability-transition-by-erk-cyclophilin-d-axis-contributes-to-the-neuroprotective-effect-of-gallic-acid-against-cerebral-ischemia-reperfusion-injury
#14
Jing Sun, Da-Dui Ren, Jin-Yi Wan, Chen Chen, Dong Chen, Huan Yang, Chun-Lai Feng, Jing Gao
Ischemic stroke is a devastating disease with complex pathophysiology. Much evidence confirms that opening of the mitochondrial permeability transition pore (MPTP) is related with mitochondrial dysfunction to apoptosis in ischemic stroke, thus elucidating its signaling mechanism and screening novel MPTP inhibitor is therefore of paramount importance. Our earlier studies identified that gallic acid (GA), a naturally occurring plant phenol, endows with effect on inhibition of mitochondrial dysfunction, which has significant neuroprotective effect in cerebral ischemia/reperfusion injury...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28428745/decreased-levels-of-foldase-and-chaperone-proteins-are-associated-with-an-early-onset-amyotrophic-lateral-sclerosis
#15
Melania Filareti, Silvia Luotti, Laura Pasetto, Mauro Pignataro, Katia Paolella, Paolo Messina, Elisabetta Pupillo, Massimiliano Filosto, Christian Lunetta, Jessica Mandrioli, Giuseppe Fuda, Andrea Calvo, Adriano Chiò, Massimo Corbo, Caterina Bendotti, Ettore Beghi, Valentina Bonetto
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive upper and lower motor neuron degeneration. One of the peculiar clinical characteristics of ALS is the wide distribution in age of onset, which is probably caused by different combinations of intrinsic and exogenous factors. We investigated whether these modifying factors are converging into common pathogenic pathways leading either to an early or a late disease onset. This would imply the identification of phenotypic biomarkers, that can distinguish the two populations of ALS patients, and of relevant pathways to consider in a therapeutic intervention...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28425861/role-of-cysteine-residues-in-regulation-of-peptidyl-prolyl-cis-trans-isomerase-activity-of-wheat-cyclophilin-tacypa-1
#16
Gundeep Kaur, Harpreet Singh, Kirandeep Kaur, Suchismita Roy, Ashwani Pareek, Prabhjeet Singh
Oxidative conditions result in inhibition of peptidyl-prolyl cis-trans isomerase (PPIase) activity of several cyclophilins. Thiol groups have been implicated in redox regulation of these proteins. In our previous study, we proposed that activity of wheat cyclophilin, TaCYPA-1, may be modulated through a novel dual mechanism of redox regulation. To further understand the regulation of PPIase activity of TaCYPA-1, we generated mutants of TaCYPA-1 by substituting cysteine residues at positions -40 and -122 with serine, and at -126 with proline...
April 17, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28409506/characterization-of-cyclophilin-d-in-freshwater-pearl-mussel-hyriopsis-schlegelii
#17
Xiu-Xiu Liu, Cheng-Yuan Wang, Chun Luo, Jun-Qing Sheng, Di Wu, Bei-Juan Hu, Jun-Hua Wang, Yi-Jiang Hong
Cyclophilin D (referred to as HsCypD) was obtained from the freshwater pearl mussel (Hyriopsis schlegelii). The full-length cDNA was 2 671 bp, encoding a protein consisting of 367 amino acids. HsCypD was determined to be a hydrophilic intracellular protein with 10 phosphorylation sites and four tetratricopeptide repeat (TPR) domains, but no signal peptide. The core sequence region YKGCIFHRIIKDFMVQGG is highly conserved in vertebrates and invertebrates. Phylogenetic tree analysis indicated that CypD from all species had a common origin, and HsCypD had the closest phylogenetic relationship with CypD from Lottia gigantea...
March 18, 2017: Zoological Research
https://www.readbyqxmd.com/read/28401933/bcl-xl-mediates-ripk3-dependent-necrosis-in-m-tuberculosis-infected-macrophages
#18
X Zhao, N Khan, H Gan, F Tzelepis, T Nishimura, S-Y Park, M Divangahi, H G Remold
Virulent Mycobacterium tuberculosis (Mtb) triggers necrosis in host Mϕ, which is essential for successful pathogenesis in tuberculosis. Here we demonstrate that necrosis of Mtb-infected Mϕ is dependent on the action of the cytosolic Receptor Interacting Protein Kinase 3 (RIPK3) and the mitochondrial Bcl-2 family member protein B-cell lymphoma-extra large (Bcl-xL). RIPK3-deficient Mϕ are able to better control bacterial growth in vitro and in vivo. Mechanistically, cytosolic RIPK3 translocates to the mitochondria where it promotes necrosis and blocks caspase 8-activation and apoptosis via Bcl-xL...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28396838/thermo-kinetic-analysis-space-expansion-for-cyclophilin-ligand-interactions-identification-of-a-new-nonpeptide-inhibitor-using-biacore%C3%A2-t200
#19
Martin A Wear, Matthew W Nowicki, Elizabeth A Blackburn, Iain W McNae, Malcolm D Walkinshaw
We have established a refined methodology for generating surface plasmon resonance sensor surfaces of recombinant his-tagged human cyclophilin-A. Our orientation-specific stabilisation approach captures his-tagged protein under 'physiological conditions' (150 mm NaCl, pH 7.5) and covalently stabilises it on Ni(2+)-nitrilotriacetic acid surfaces, very briefly activated for primary amine-coupling reactions, producing very stable and active surfaces (≥ 95% specific activity) of cyclophilin-A. Variation in protein concentration with the same contact time allows straightforward generation of variable density surfaces, with essentially no loss of activity, making the protocol easily adaptable for studying numerous interactions; from very small fragments, ~ 100 Da, to large protein ligands...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28394340/selective-targeting-p53-wt-lung-cancer-cells-harboring-homozygous-p53-arg72-by-an-inhibitor-of-cypa
#20
W Lu, F Cheng, W Yan, X Li, X Yao, W Song, M Liu, X Shen, H Jiang, J Chen, J Li, J Huang
TP53 plays essential roles in tumor initiation and progression, and is frequently mutated in cancer. However, pharmacological stabilization and reactivation of p53 have not been actively explored for targeted cancer therapies. Herein, we identify a novel Cyclophilin A (CypA) small molecule inhibitor (HL001) that induces non-small cell lung cancer (NSCLC) cell cycle arrest and apoptosis via restoring p53 expression. We find that HL001 stabilizes p53 through inhibiting the MDM2-mediated p53 ubiquitination. Further mechanistic studies reveal that the downregulation of G3BP1 and the induction of reactive oxygen species and DNA damage by HL001 contribute to p53 stabilization...
April 10, 2017: Oncogene
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