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https://www.readbyqxmd.com/read/28105238/immune-associated-proteins-with-potential-in-vivo-anti-tumor-activities-are-upregulated-in-lung-cancer-cells-treated-with-umbelliprenin-a-proteomic-approach
#1
Narges Khaghanzadeh, Kazuyuki Nakamura, Yasuhiro Kuramitsu, Abbas Ghaderi, Zahra Mojtahedi
Umbelliprenin (Umb), a natural coumarin, has demonstrated anti-tumor activities, both in vitro and particularly in vivo, in several types of cancer, including lung cancer. The present study aimed to identify molecular targets of Umb using a high-throughput approach. Lung cancer cell lines, QU-DB (large-cell lung carcinoma) and A549 (adenocarcinoma), were treated with Umb. Differentially-expressed proteins were identified using two-dimensional electrophoresis coupled to mass spectrometry. In the QU-DB cells, differential expression of proteins, including downregulation of the tumorigenic protein heat shock protein 90 kDa and upregulation of the potential anti-tumor proteins Nipsnap1 and glycine-tRNA ligase (GRS), suggested that Umb is a strong anti-tumor compound...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105234/interaction-of-cyclophilin-a-with-a-novel-binding-protein-sr-25-and-characterization-of-their-expression-pattern-in-chinese-hepatocellular-carcinoma-patients
#2
Jian Chen, Ning Li, Peiwen Lian, Jiahui Wang, Peng Li, Zhaohua Gong, Lixin Jiang
Cyclophilin (Cyp) A has been reported to be overexpressed in the majority of cancer cells, including hepatocellular carcinoma (HCC). However, the biological functions of CypA in HCC are far from being understood. To determine the biological functions of CypA in HCC, the present study screened human fetal liver complementary DNA for proteins interacting with CypA using the yeast two-hybrid system. A nuclear protein, serine/arginine-rich (SR)-25, was isolated as a novel CypA-binding protein that is distinct from those previously described in the literature...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28089447/networks-of-dynamic-allostery-regulate-enzyme-function
#3
Michael Joseph Holliday, Carlo Camilloni, Geoffrey Stuart Armstrong, Michele Vendruscolo, Elan Zohar Eisenmesser
Many protein systems rely on coupled dynamic networks to allosterically regulate function. However, the broad conformational space sampled by non-coherently dynamic systems has precluded detailed analysis of their communication mechanisms. Here, we have developed a methodology that combines the high sensitivity afforded by nuclear magnetic resonance relaxation techniques and single-site multiple mutations, termed RASSMM, to identify two allosterically coupled dynamic networks within the non-coherently dynamic enzyme cyclophilin A...
December 27, 2016: Structure
https://www.readbyqxmd.com/read/28079595/acetylated-cyclophilin-a-is-a-major-mediator-in-hypoxia-induced-autophagy-and-pulmonary-vascular-angiogenesis
#4
Min Mao, Xiufeng Yu, Xin Ge, Rui Gu, Qian Li, Shasha Song, Xiaodong Zheng, Tingting Shen, Xuecang Li, Yao Fu, Jiali Li, Daling Zhu
BACKGROUND: Autophagy is a major intracellular degradation and recycling process that maintains cellular homeostasis, which is involved in structural and functional abnormalities of pulmonary vasculature in hypoxic pulmonary arterial hypertension (HPAH). Cyclophilin A (CyPA) is a secreted, oxidative stress-induced factor. Its role in inducing autophagy and augmenting endothelial cell dysfunction has never been explored. METHODS: Lungs from rats exposed to chronic hypoxia were examined for autophagy with electron microscopy, western blotting, and fluorescence microscopy...
January 12, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28077629/sun2-silencing-impairs-cd4-t-cell-proliferation-and-alters-sensitivity-to-hiv-1-infection-independently-of-cyclophilin-a
#5
Daniel A Donahue, Françoise Porrot, Norbert Couespel, Olivier Schwartz
: Linker of nucleoskeleton and cytoskeleton (LINC) complexes connect the nucleus to the cytoskeleton in eukaryotic cells. We previously reported that overexpression of SUN2, an inner nuclear membrane protein and LINC complex component, inhibits HIV infection between reverse transcription and nuclear import in a capsid-specific manner. We also reported that SUN2 silencing does not modulate HIV infection in several cell lines. Silencing of SUN2 was recently reported to decrease HIV infection of CD4 T cells, an effect suggested to result from modulation of CypA-dependent steps of HIV infection...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28076787/impdh2-is-an-intracellular-target-of-the-cyclophilin-a-and-sanglifehrin-a-complex
#6
Khian Hong Pua, Dylan T Stiles, Mathew E Sowa, Gregory L Verdine
Natural products have demonstrated utility in the clinic and can also act as probes to understand complex cellular pathways. Sanglifehrin A (SFA) is a mixed polyketide and non-ribosomal peptide synthase natural product with sub-nano-molar affinity for its receptor cyclophilin A (PPIA). It has been shown to behave in vitro as an immune suppressant. Here, we identify inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) as an intracellular target of the PPIA-SFA binary complex. The formation of this ternary complex does not inhibit the enzymatic activity of IMPDH2...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28075591/discovery-of-potent-cyclophilin-inhibitors-based-on-structural-simplification-of-sanglifehrin-a
#7
Victoria A Steadman, Simon B Pettit, Karine G Poullennec, Linos Lazarides, Andrew J Keats, David K Dean, Steven J Stanway, Carol A Austin, Jonathan A Sanvoisin, Gregory M Watt, Hans G Fliri, Albert C Liclican, Debi Jin, Melanie H Wong, Stephanie A Leavitt, Yu-Jen Lee, Yang Tian, Christian R Frey, Todd C Appleby, Uli Schmitz, Petr Jansa, Richard L Mackman, Brian Edward Schultz
Cyclophilin inhibition has been a target for the treatment of hepatitis C and other diseases, but the generation of potent, drug-like molecules through chemical synthesis has been challenging. In this study, a set of macrocyclic cyclophilin inhibitors was synthesized based on the core structure of the natural product sanglifehrin A. Initial compound optimization identified the valine-m-tyrosine-piperazic acid tripeptide (Val-m-Tyr-Pip) in the sanglifehrin core, stereocenters at C14 and C15, and the hydroxyl group of the m-tyrosine (m-Tyr) residue as key contributors to compound potency...
January 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28074922/soybean-cyclophilin-gmcyp1-interacts-with-an-isoflavonoid-regulator-gmmyb176
#8
Hemanta Raj Mainali, Arun Kumaran Anguraj Vadivel, Xuyan Li, Mark Gijzen, Sangeeta Dhaubhadel
Cyclophilins (CYPs) belong to the immunophilin superfamily with peptidyl-prolyl cis-trans isomerase (PPIase) activity. They catalyze the interconversion of the cis- and trans-rotamers of the peptidyl-prolyl amide bond of peptides. A yeast-two-hybrid screening using the isoflavonoid regulator GmMYB176 as bait identified GmCYP1 as one of the interacting proteins in soybean embryos. GmCYP1 localizes both in the nucleus and cytoplasm, and interacts in planta with GmMYB176, in the nucleus, and with SGF14l (a soybean 14-3-3 protein) in the nucleus and the cytoplasm...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28065786/cisplatin-induced-necroptosis-in-tnf%C3%AE-dependent-and-independent-pathways
#9
Yanfang Xu, Hua-Bin Ma, Yu-Lu Fang, Zhi-Rong Zhang, Jing Shao, Mao Hong, Chao-Jun Huang, Jing Liu, Rui-Qing Chen
Cisplatin is a chemotherapeutic drug for treatment of many solid tumors. It has been shown to induce apoptosis and/or necrosis in different types of cancer cells. However, the underlying mechanisms remain elusive. In this study, we provide evidences that cisplatin induces necroptosis in receptor-interacting protein 3 (RIP3)-expressing cell lines, but not in cell lines lacking RIP3 protein expression. Deficiency of core components of necroptotic pathway, RIP1, RIP3, or mixed lineage kinase domain-like protein (MLKL) blocked cisplatin-induced cell death in L929 cells...
January 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28062572/updates-in-understanding-the-role-of-cyclophilin-a-in-leukocyte-chemotaxis
#10
REVIEW
Farman Ullah Dawar, Junjie Wu, Lijuan Zhao, Muhammad Nasir Khan Khattak, Jie Mei, Li Lin
Cyclophilin A (CypA), a well-recognized receptor for anti-inflammatory drug cyclosporine A (CsA) is a ubiquitous and multifunctional protein. Beside the diverse intracellular functions, CypA is secreted against inflammatory stimuli, where it activates and attracts leukocytes via CD147 to the stimulus site. Interestingly, it synergizes with other factors to induce leukocyte migration in different animals. However, the silencing and inhibition of CypA or CD147 inhibits leukocytes chemotaxis and inflammation. This review focuses on the advances made in understanding the mechanism of CypA-dependent leukocytes chemotaxis and hence, recognition of this factor as a possible therapeutic target in inflammatory diseases...
January 6, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28060261/study-of-endoplasmic-reticulum-and-mitochondria-interactions-by-in-situ-proximity-ligation-assay-in-fixed-cells
#11
Emily Tubbs, Jennifer Rieusset
Structural interactions between the endoplasmic reticular (ER) and mitochondrial membranes, in domains known as mitochondria-associated membranes (MAM), are crucial hubs for cellular signaling and cell fate. Particularly, these inter-organelle contact sites allow the transfer of calcium from the ER to mitochondria through the voltage-dependent anion channel (VDAC)/glucose-regulated protein 75 (GRP75)/inositol 1,4,5-triphosphate receptor (IP3R) calcium channeling complex. While this subcellular compartment is under intense investigation in both physiological and pathological conditions, no simple and sensitive method exists to quantify the endogenous amount of ER-mitochondria contact in cells...
December 10, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28058638/functional-analysis-of-the-two-cyclophilin-isoforms-of-sinorhizobium-meliloti
#12
Eirini-Evangelia Thomloudi, Aggeliki Skagia, Anastasia Venieraki, Panagiotis Katinakis, Maria Dimou
The nitrogen fixing Sinorhizobium meliloti possesses two genes, ppiA and ppiB, encoding two cyclophilin isoforms which belong to the superfamily of peptidyl prolyl cis/trans isomerases (PPIase, EC: 5.2.1.8). Here, we functionally characterize the two proteins and we demonstrate that both recombinant cyclophilins are able to isomerise the Suc-AAPF-pNA synthetic peptide but neither of them displays chaperone function in the citrate synthase thermal aggregation assay. Furthermore, we observe that the expression of both enzymes increases the viability of E...
February 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28053189/function-of-cyclophilin1-as-a-long-distance-signal-molecule-in-the-phloem-of-tomato-plants
#13
Ziv Spiegelman, Sumita Omer, Ben N Mansfeld, Shmuel Wolf
Tomato (Solanum lycopersicum) diageotropica (dgt) mutants, containing a single mutation in the Cyclophilin1 (SlCyp1) gene, are auxin-insensitive, exhibiting a pleiotropic phenotype including lack of geotropism, abnormal xylem structure, lack of lateral roots (LRs), and elevated shoot-to-root ratio. SlCyp1 is a putative peptidyl-prolyl isomerase that can traffic from shoot to root, where it induces changes in auxin response, LR formation, and xylem development, suggesting it has a role as a long-distance signaling molecule...
January 4, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28038796/cyclophilin-a-mediates-the-ox-ldl-induced-activation-and-apoptosis-of-macrophages-via-autophagy
#14
Zhiqiang Xue, Wei Yuan, Jing Li, Hong Zhou, Lihua Xu, Jiayi Weng, Xiaoyang Li, Xinru Zhang, Zhongqun Wang, Jinchuan Yan
BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) is the most common inflammatory factor that mediates the activation and apoptosis of macrophages. Cyclophilin A (CyPA) is expressed following oxidative stress, hypoxia, and infection. However, the role of CyPA in the activation and apoptosis of macrophages is unclear. The aims of the study were to determine whether CyPA mediates the ox-LDL-induced activation and apoptosis in RAW264.7 cells and to analyze potential mechanisms. METHODS AND RESULTS: Through Western blot and ELISA test, the expression of CyPA induced by ox-LDL is time-dependent in RAW264...
December 19, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28035667/acceleration-of-protein-backbone-nmr-assignment-by-combinatorial-labeling-application-to-a-small-molecule-binding-study
#15
Christopher Hein, Frank Löhr, Daniel Schwarz, Volker Dötsch
Selective labeling with stable isotopes has long been recognized as a valuable tool in protein NMR to alleviate signal overlap and sensitivity limitations. In this study, combinatorial (15) N-, (13) C(α) -, and (13) C'-selective labeling has been used during the backbone assignment of human cyclophilin D to explore binding of an inhibitor molecule. Using a cell-free expression system, a scheme that involves (15) N, 1-(13) C, 2-(13) C, fully (15) N/(13) C, and unlabeled amino acids was optimized to gain a maximum of assignment information from three samples...
December 30, 2016: Biopolymers
https://www.readbyqxmd.com/read/28011744/targeting-extracellular-cyclophilin-a-reduces-neuroinflammation-and-extends-survival-in-a-mouse-model-of-amyotrophic-lateral-sclerosis
#16
Laura Pasetto, Silvia Pozzi, Mariachiara Castelnovo, Manuela Basso, Alvaro G Estevez, Stefano Fumagalli, Maria Grazia De Simoni, Valeria Castellaneta, Paolo Bigini, Elena Restelli, Roberto Chiesa, Francesca Trojsi, Maria Rosaria Monsurrò, Leonardo Callea, Miroslav Malešević, Gunter Fischer, Mattia Freschi, Massimo Tortarolo, Caterina Bendotti, Valentina Bonetto
: Neuroinflammation is a major hallmark of amyotrophic lateral sclerosis (ALS), which is currently untreatable. Several anti-inflammatory compounds have been evaluated in patients and animal models of ALS, but have been proved disappointing, in part because effective targets have not yet been identified. Cyclophilin A (PPIA) as a foldase is beneficial intracellularly, but extracellularly has detrimental functions. We found that extracellular PPIA is a mediator of neuroinflammation in ALS...
December 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28011625/gastric-cancer-cell-proliferation-and-survival-is-enabled-by-a-cyclophilin-b-stat3-microrna-520d-5p-signaling-feedback-loop
#17
Ting Li, Hanqing Guo, Xiaodi Zhao, Jiang Jin, Lifeng Zhang, Hong Li, Yuanyuan Lu, Yongzan Nie, Kaichun Wu, Yongquan Shi, Daiming Fan
Molecular links between inflammation and cancer remain obscure despite their great pathogenic significance. The JAK2/STAT3 pathway activated by IL-6 and other pro-inflammatory cytokines has garnered attention as a pivotal link in cancer pathogenesis, but the basis for its activation in cancer cells is not understood. Here we report that an IL-6-triggered feedback loop involving STAT3-mediated suppression of miR-520d-5p and its downstream target cyclophilin B (CypB) regulates the growth and survival of gastric cancer cells...
December 23, 2016: Cancer Research
https://www.readbyqxmd.com/read/28009548/conformational-variation-of-proteins-at-room-temperature-is-not-dominated-by-radiation-damage
#18
Silvia Russi, Ana González, Lillian R Kenner, Daniel A Keedy, James S Fraser, Henry van den Bedem
Protein crystallography data collection at synchrotrons is routinely carried out at cryogenic temperatures to mitigate radiation damage. Although damage still takes place at 100 K and below, the immobilization of free radicals increases the lifetime of the crystals by approximately 100-fold. Recent studies have shown that flash-cooling decreases the heterogeneity of the conformational ensemble and can hide important functional mechanisms from observation. These discoveries have motivated increasing numbers of experiments to be carried out at room temperature...
January 1, 2017: Journal of Synchrotron Radiation
https://www.readbyqxmd.com/read/28005946/the-mitochondrial-permeability-transition-pore-regulator-cyclophilin-d-exhibits-tissue-specific-control-of-metabolic-homeostasis
#19
Rhianna C Laker, Evan P Taddeo, Yasir N Akhtar, Mei Zhang, Kyle L Hoehn, Zhen Yan
The mitochondrial permeability transition pore (mPTP) is a key regulator of mitochondrial function that has been implicated in the pathogenesis of metabolic disease. Cyclophilin D (CypD) is a critical regulator that directly binds to mPTP constituents to facilitate the pore opening. We previously found that global CypD knockout mice (KO) are protected from diet-induced glucose intolerance; however, the tissue-specific function of CypD and mPTP, particularly in the control of glucose homeostasis, has not been ascertained...
2016: PloS One
https://www.readbyqxmd.com/read/27993675/the-cyclophilin-d-drp1-axis-regulates-mitochondrial-fission-contributing-to-oxidative-stress-induced-mitochondrial-dysfunctions-in-sh-sy5y-cells
#20
Anqi Xiao, Xueqi Gan, Ruiqi Chen, Yanming Ren, Haiyang Yu, Chao You
Oxidative stress plays a central role in the pathogenesis of various neurodegenerative diseases. Increasing evidences have demonstrated that structural abnormalities in mitochondria are involved in oxidative stress related nerve cell damage. And Drp1 plays a critical role in mitochondrial dynamic imbalance insulted by oxidative stress-derived mitochondria. However, the status of mitochondrial fusion and fission pathway and its relationship with mitochondrial properties such as mitochondrial membrane permeability transition pore (mPTP) have not been fully elucidated...
December 18, 2016: Biochemical and Biophysical Research Communications
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