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Sebastian Schloer, Denise Pajonczyk, Ursula Rescher
The vertebrate annexin superfamily (AnxA) consists of 12 members of a calcium (Ca2+ ) and phospholipid binding protein family which share a high structural homology. In keeping with this hallmark feature, annexins have been implicated in the Ca2+ -controlled regulation of a broad range of membrane events. In this review, we identify and discuss several themes of annexin actions that hold a potential therapeutic value, namely, the regulation of the immune response and the control of tissue homeostasis, and that repeatedly surface in the annexin activity profile...
June 15, 2018: International Journal of Molecular Sciences
Carles Rentero, Patricia Blanco-Muñoz, Elsa Meneses-Salas, Thomas Grewal, Carlos Enrich
The spatiotemporal regulation of calcium (Ca2+ ) storage in late endosomes (LE) and lysosomes (Lys) is increasingly recognized to influence a variety of membrane trafficking events, including endocytosis, exocytosis, and autophagy. Alterations in Ca2+ homeostasis within the LE/Lys compartment are implicated in human diseases, ranging from lysosomal storage diseases (LSDs) to neurodegeneration and cancer, and they correlate with changes in the membrane binding behaviour of Ca2+ -binding proteins. This also includes Annexins (AnxA), which is a family of Ca2+ -binding proteins participating in membrane traffic and tethering, microdomain organization, cytoskeleton interactions, Ca2+ signalling, and LE/Lys positioning...
May 12, 2018: International Journal of Molecular Sciences
Samuele Negro, Marco Stazi, Marta Marchioretto, Toma Tebaldi, Umberto Rodella, Elisa Duregotti, Volker Gerke, Alessandro Quattrone, Cesare Montecucco, Michela Rigoni, Gabriella Viero
Schwann cells are key players in neuro-regeneration: they sense alarm signals released by degenerating nerve terminals and differentiate toward a pro-regenerative phenotype, with phagocytosis of nerve debris and nerve guidance. At the murine neuromuscular junction, hydrogen peroxide (H2 O2 ) is a key signal of Schwann cells activation in response to a variety of nerve injuries. Here we report that Schwann cells exposed to low doses of H2 O2 rewire the expression of several RNAs at both transcriptional and translational levels...
April 11, 2018: RNA
Numfa Fungbun, Doungrut Tungmahasuk, Ryota Terashima, Shiro Kurusu, Mitsumori Kawaminami
Gonadotropin-releasing hormone (GnRH) regulates gonadotropin secretion. We previously demonstrated that the expression of annexin A5 (ANXA5) is stimulated by GnRH in gonadotropes and has a significant role in gonadotropin secretion. It is therefore of interest to know whether other members of the ANXA family, which consists of twelve structurally related members, are also regulated by GnRH. Therefore, the expression of all annexins was examined in LβT2 gonadotrope cells. ANXA4, A5, A6, A7 and A11 were detected in LβT2 cells...
January 27, 2018: Journal of Veterinary Medical Science
H K Knych, L Harrison, N Chouicha, P H Kass
BACKGROUND: Intra-articular use of corticosteroids is commonplace in performance horses. Isoflupredone acetate (IPA) is one of four Food and Drug Administration approved corticosteroids for intra-articular use in horses. The lack of published reports describing the efficacy and duration of effects of this drug warrant further study. OBJECTIVES: To assess the effects of intra-articular administration of IPA on the expression of selected anti and pro inflammatory and structural matrix genes following intra-articular administration to exercised Thoroughbred horses and to correlate these effects with drug concentrations...
October 17, 2017: Equine Veterinary Journal
Kátia M Lima, Juliana P Vago, Thaís R Caux, Graziele Letícia Negreiros-Lima, Michelle A Sugimoto, Luciana P Tavares, Raquel G Arribada, Aline Alves F Carmo, Izabela Galvão, Bruno Rocha C Costa, Frederico M Soriani, Vanessa Pinho, Egle Solito, Mauro Perretti, Mauro M Teixeira, Lirlândia P Sousa
Annexin A1 (AnxA1) is a glucocorticoid-regulated protein known for its anti-inflammatory and pro-resolving effects. We have shown previously that the cAMP-enhancing compounds rolipram (ROL; a PDE4 inhibitor) and Bt2 cAMP (a cAMP mimetic) drive caspase-dependent resolution of neutrophilic inflammation. In this follow-up study, we investigated whether AnxA1 could be involved in the pro-resolving properties of these compounds using a model of LPS-induced inflammation in BALB/c mice. The treatment with ROL or Bt2 cAMP at the peak of inflammation shortened resolution intervals, improved resolution indices, and increased AnxA1 expression...
August 18, 2017: Journal of Biological Chemistry
Julia Kälsch, Juliet Padden, Stefanie Bertram, Leona L Pott, Henning Reis, Daniela Westerwick, Christoph M Schaefer, Jan-P Sowa, Dorothe Möllmann, Christian Fingas, Alexander Dechȇne, Barbara Sitek, Martin Eisenacher, Ali Canbay, Maike Ahrens, Hideo A Baba
Discriminating intrahepatic cholangiocarcinoma (ICC) from hepatic metastases of pancreatic ductal adenocarcinoma (mPDAC) can be challenging. While pathologists might depend on clinical information regarding a primary tumor, their diagnosis will lead the patient either to potentially curative surgery (for ICC) or to palliation (for mPDAC). Beyond the validation of recently published potential biomarkers for PDAC (primary or metastatic) in a large cohort, we assessed diagnostic performance of the most promising candidates in the challenging task of discriminating metastatic PDAC (mPDAC) from ICC...
May 2017: Virchows Archiv: An International Journal of Pathology
Isa N Cruz, Helen M Coley, Holger B Kramer, Thumuluru Kavitah Madhuri, Nur A M Safuwan, Ana Rita Angelino, Min Yang
BACKGROUND: Carboplatin and paclitaxel form the cornerstone of chemotherapy for epithelial ovarian cancer, however, drug resistance to these agents continues to present challenges. Despite extensive research, the mechanisms underlying this resistance remain unclear. MATERIALS AND METHODS: A 2D-gel proteomics method was used to analyze protein expression levels of three human ovarian cancer cell lines and five biopsy samples. Representative proteins identified were validated via western immunoblotting...
January 2, 2017: Cancer Genomics & Proteomics
Maria-Pilar Fernandez, Montserrat Garcia, Silvia Martin-Almedina, Reginald O Morgan
The fundamental cellular role and molecular interactions of annexins in vesicle trafficking and membrane remodeling remain to be further clarified in order to better understand and exploit their contributions to health and disease. We focused on distinctive features of atypical annexins from all domains of life using phylogenomic, molecular systematic and experimental approaches, to extend the current paradigm and better account for annexin diversity of structure, function and mechanistic role in membrane homeostasis...
June 27, 2017: Biological Chemistry
Zaynab Mousavian, Abbas Nowzari-Dalini, Ronald W Stam, Yasir Rahmatallah, Ali Masoudi-Nejad
PURPOSE: Despite vast improvements that have been made in the treatment of children with acute lymphoblastic leukemia (ALL), the majority of infant ALL patients (~80 %, < 1 year of age) that carry a chromosomal translocation involving the mixed lineage leukemia (MLL) gene shows a poor response to chemotherapeutic drugs, especially glucocorticoids (GCs), which are essential components of all current treatment regimens. Although addressed in several studies, the mechanism(s) underlying this phenomenon have remained largely unknown...
February 2017: Cellular Oncology (Dordrecht)
Ying Liu, Ying Liao, Linlin Xiang, Kuo Jiang, Siyao Li, Mingmei Huangfu, Shilong Sun
BACKGROUND: Specific circulating autoantibodies are produced by host immune systems to respond to antigens that arise during tumorigenesis. To achieve auxiliary diagnosis, the present study was designed to test whether circulating autoantibodies against tumor-associated antigens (TAAs) were altered in early breast cancer. METHODS: A total of 102 breast cancer patients and 146 age-matched healthy volunteers were recruited to participate in this study. Autoantibody expression was tested using in-house developed enzyme-linked immunosorbent assay (ELISA) with linear peptide envelope antigens derived from TAAs...
April 2017: International Journal of Clinical Oncology
Florie Mar, Mark Crowther, Alex Gold, Genmin Lu, Janet Leeds, Brian Wiens, Vandana Mathur, Janice Castillo, Pamela Conley, Stuart Connolly, John Curnutte
INTRODUCTION: Direct FXa inhibitors have demonstrated convincing anticoagulant efficacy. However, risk of major bleeding is a concern and no specific antidotes are available for reversal. Andexanet alfa (AnXa), a recombinant modified FXa, is an investigational specific antidote for FXa inhibitors. We report data from the ANNEXA"! Phase 3 registration studies in older healthy subjects anticoagulated with apixaban (apix) or rivaroxaban (riva). METHODS: ANNEXA A&R were 2 phase 3, randomized, double-blind, placebo-controlled studies of AnXa in healthy subjects age 50 to 75 administered either apixaban or rivaroxaban...
August 2016: Neurosurgery
Dianhui Xiu, Lin Liu, Fengli Qiao, Haishan Yang, Lu Cui, Guifeng Liu
The present study aimed to reveal the expression of STAT3 and Anxa 2 in CRC specimens and to investigate the effects of STAT3 and Anxa 2 signaling on the proliferation, invasion, and migration in CRC Caco-2 cells. Results demonstrated that both Anxa 2 and STAT3 were highly expressed in CRC specimens in both mRNA and protein levels, with or without phosphorylation (Tyrosine 23 in Anxa 2 and Tyrosine 705 in STAT3). And the upregulated Anxa 2 promoted the phosphorylation of STAT3 (Tyrosine 705) in CRC Caco-2 cells...
2016: Gastroenterology Research and Practice
H F Yuan, Y Li, B B Tan, Q Zhao, L Q Fan, W H Ye
OBJECTIVE: To investigate the expression of annexin A7 (ANXA7) in the differentiation and lymphatic metastasis of gastric cancer (GC), and to investigate the relationship between ANXA7 and biological characteristics of GC. METHODS: The clinicopathological data of 124 patients with gastric cancer who underwent surgical treatment in our hospital were retrospectively reviewed and analyzed. Immunohistochemical staining and Western blot were performed to analyze the expression of ANXA 7 in primary GC tissues...
May 23, 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Qifeng Zhao, Ji Wu, Zhiyong Lin, Qingwang Hua, Weixi Zhang, Leping Ye, Guowei Wu, Jie Du, Jie Xia, Maoping Chu, Xingti Hu
Lung ischemia-reperfusion injury (LIRI) is still an unsolved medical issue, which negatively affects the prognosis of many lung diseases. The aim of this study is to determine the effects of RvD1 on LIRI and the potential mechanisms involved. The results revealed that the levels of complement, immunoglobulin, cytokines, sICAM-1, MPO, MDA, CINC-1, MCP-1, ANXA-1, TLR4, NF-κBp65, apoptosis index, and pulmonary permeability index were increased, whereas the levels of SOD, GSH-PX activity, and oxygenation index were decreased in rats with LIRI...
August 2016: Inflammation
Kamrouz Ghadimi, Keith E Dombrowski, Jerrold H Levy, Ian J Welsby
Andexanet alfa is a specific reversal agent for Factor Xa inhibitors. The molecule is a recombinant protein analog of factor Xa that binds to Factor Xa inhibitors and antithrombin:LMWH complex but does not trigger prothrombotic activity. In ex vivo, animal, and volunteer human studies, andexanet alfa (AnXa) was able to dose-dependently reverse Factor Xa inhibition and restore thrombin generation for the duration of drug administration. Further trials are underway to examine its safety and efficacy in the population of patients experiencing FXa inhibitor-related bleeding...
2016: Expert Review of Hematology
Sei-Jung Lee, Young Hyun Jung, Eun Ju Song, Kyung Ku Jang, Sang Ho Choi, Ho Jae Han
An inflammatory response is a hallmark of necrosis evoked by bacterial pathogens. Vibrio vulnificus, VvpE, is an elastase that is responsible for tissue necrosis and inflammation; however, the molecular mechanism by which it regulates host cell death has not been characterized. In the present study, we investigate the cellular mechanism of VvpE with regard to host cell death and the inflammatory response of human intestinal epithelial (INT-407) cells. The recombinant protein (r)VvpE (50 pg/ml) caused cytotoxicity mainly via necrosis coupled with IL-1β production...
September 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
De-Hong Yu, Ya-Rong Liu, Xin Luan, Hai-Jun Liu, Yun-Ge Gao, Hao Wu, Chao Fang, Hong-Zhuan Chen
Multidrug resistance is the main cause of clinical chemotherapeutic failure. Antiangiogenic cancer therapy with nanomedicine that allows the targeted delivery of antiangiogenic agents to tumor endothelial cells may contribute to innovative strategies for treating multidrug-resistant cancers. In this study, we developed a new nanodrug delivery system (nano-DDS), with improved antiangiogenic efficacy against multidrug resistant human breast cancer MCF-7/ADR cells. Here, the IF7 ligand was a peptide designed to bind the annexin 1 (Anxa 1), a highly specific marker of the tumor vasculature surface, with high affinity and specificity...
August 19, 2015: Bioconjugate Chemistry
Hu-Fang Yuan, Yong Li, Qun Zhao, Li-Qiao Fan, Bi-Bo Tan, Wei-Hua Ye
OBJECTIVE: To investigate the expression and clinical significance of annexin A7 in the differentiation and lymphatic metastasis of gastric cancer (GC). METHODS: The clinical and pathological data were recorded for analysis. Immunohistochemical staining and Western blot were performed to analyze the expression of ANXA 7 in primary GC tissues. Logistic regression analyses were conducted to evaluate the associations between annexin A7 expression levels and differentiations of GC...
2014: International Journal of Clinical and Experimental Pathology
Z Boudhraa, C Merle, D Mazzocut, J M Chezal, C Chambon, E Miot-Noirault, M Theisen, B Bouchon, F Degoul
Annexin A1 deregulation is often associated with cancer. Indeed we have shown that annexin A1 is overexpressed in melanoma and promotes metastases by formyl peptide receptor stimulation and MMP2 expression. Here, we demonstrated in different melanoma cell lines that annexin A1-MMP2 induction is mediated by MAPK and STAT3 pathways. To decipher endogenous annexin A1 action mode, we showed that annexin A1 is externalized in A375 cells and cleaved by a membrane-associated serine protease, allowing the release of a pro-invasive annexin A1 peptide in the extra cellular environment...
December 2014: Archives of Dermatological Research
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