864 results match your criteria cypa

Design, Optimization, and Structural Characterization of an Apoptosis-Inducing Factor Peptide Targeting Human Cyclophilin A to Inhibit Apoptosis Inducing Factor-Mediated Cell Death.

J Med Chem 2021 Aug 2. Epub 2021 Aug 2.

Institute of Biostructures and Bioimaging (IBB)-CNR, Via Mezzocannone, 16, 80134 Napoli, Italy.

Blocking the interaction between the apoptosis-inducing factor (AIF) and cyclophilin A (CypA) by the AIF fragment AIF(370-394) is protective against glutamate-induced neuronal cell death and brain injury in mice. Starting from AIF(370-394), we report the generation of the disulfide-bridged and shorter variant AIF(381-389) and its structural characterization by nuclear magnetic resonance (NMR) in the free and CypA-bound state. AIF(381-389) in both the free and bound states assumes a β-hairpin conformation similar to that of the fragment in the AIF protein and shows a highly reduced conformational flexibility. Read More

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The Role of Cyclophilins in Inflammatory Bowel Disease and Colorectal Cancer.

Int J Biol Sci 2021 16;17(10):2548-2560. Epub 2021 Jun 16.

Department of Pathogenic Biology and Immunology, School of Life Sciences and Biopharmaceuticals, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong Province, PR China.

Cyclophilins (Cyps) is a kind of ubiquitous protein family in organisms, which has biological functions such as promoting intracellular protein folding and participating in the pathological processes of inflammation and tumor. Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are two common intestinal diseases, but the etiology and pathogenesis of these two diseases are still unclear. IBD and CRC are closely associated, IBD has always been considered as one of the main risks of CRC. Read More

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Induction of CIITA by IFN-γ in macrophages involves STAT1 activation by JAK and JNK.

Immunobiology 2021 Jul 14;226(5):152114. Epub 2021 Jul 14.

Macrophage Biology Group, Department of Cellular Biology, Physiology and Immunology, Universitat de Barcelona, Barcelona, Spain. Electronic address:

The induction of major histocompatibility complex (MHC) class II proteins by interferon gamma (IFN-γ) in macrophages play an important role during immune responses. Here we explore the signaling pathways involved in the induction by IFN-γ of the MHC II transactivator (CIIta) required for MHC II transcriptional activation. Cyclophilin A (CypA) is required for IFN-γ-dependent induction of MHC II in macrophages, but not when it is mediated by GM-CSF. Read More

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SARS-CoV-2 Entry: At the Crossroads of CD147 and ACE2.

Cells 2021 06 8;10(6). Epub 2021 Jun 8.

Cancer Imaging Unit, Experimental Imaging Centre, IRCCS San Raffaele Scientific Institute, 20132 Milano, Italy.

In late 2019, the betacoronavirus SARS-CoV-2 was identified as the viral agent responsible for the coronavirus disease 2019 (COVID-19) pandemic. Coronaviruses Spike proteins are responsible for their ability to interact with host membrane receptors and different proteins have been identified as SARS-CoV-2 interactors, among which Angiotensin-converting enzyme 2 (ACE2), and Basigin2/EMMPRIN/CD147 (CD147). CD147 plays an important role in human immunodeficiency virus type 1, hepatitis C virus, hepatitis B virus, Kaposi's sarcoma-associated herpesvirus, and severe acute respiratory syndrome coronavirus infections. Read More

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In Silico Evaluation of Cyclophilin Inhibitors as Potential Treatment for SARS-CoV-2.

Open Forum Infect Dis 2021 Jun 14;8(6):ofab189. Epub 2021 Apr 14.

Center for Biologics Evaluation and Research, Office of Tissues and Advanced Therapies, Division of Plasma Protein Therapeutics, Food and Drug Administration, Silver Spring, Maryland, USA.

Background: The advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provoked researchers to propose multiple antiviral strategies to improve patients' outcomes. Studies provide evidence that cyclosporine A (CsA) decreases SARS-CoV-2 replication in vitro and decreases mortality rates of coronavirus disease 2019 (COVID-19) patients. CsA binds cyclophilins, which isomerize prolines, affecting viral protein activity. Read More

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Interplay among Conformation, Intramolecular Hydrogen Bonds, and Chameleonicity in the Membrane Permeability and Cyclophilin A Binding of Macrocyclic Peptide Cyclosporin O Derivatives.

J Med Chem 2021 Jun 7;64(12):8272-8286. Epub 2021 Jun 7.

Department of Chemistry, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea.

A macrocyclic peptide scaffold with well-established structure-property relationship is desirable for tackling undruggable targets. Here, we adopted a natural macrocycle, cyclosporin O () and its derivatives (-), and evaluated the impact of conformation on membrane permeability, cyclophilin A (CypA) binding, and the pharmacokinetic (PK) profile. In nonpolar media, showed a similar conformation to cyclosporin A (), a well-known chameleonic macrocycle, but less chameleonic behavior in a polar environment. Read More

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Activated ERK Signaling Is One of the Major Hub Signals Related to the Acquisition of Radiotherapy-Resistant MDA-MB-231 Breast Cancer Cells.

Int J Mol Sci 2021 May 6;22(9). Epub 2021 May 6.

Departments of Internal Medicine, Institute of Health Sciences and Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, 90 Chilam-dong, Jinju 660-702, Korea.

Breast cancer is one of the major causes of deaths due to cancer, especially in women. The crucial barrier for breast cancer treatment is resistance to radiation therapy, one of the important local regional therapies. We previously established and characterized radio-resistant MDA-MB-231 breast cancer cells (RT-R-MDA-MB-231 cells) that harbor a high expression of cancer stem cells (CSCs) and the EMT phenotype. Read More

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The CypA-netics of Ventilator-Induced Lung Injury.

Am J Respir Crit Care Med 2021 May 25. Epub 2021 May 25.

Institute of Physiology. Charité Universitätsmedizin, Berlin, Germany.

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Enantioselective Synthesis and Biological Evaluation of Sanglifehrin A and B and Analogs.

Angew Chem Int Ed Engl 2021 Jul 24;60(31):17045-17052. Epub 2021 Jun 24.

Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford St, Cambridge, MA, 02138, USA.

Sanglifehrin A and B are immunosuppressive macrocyclic natural products endowed with and differentiated by a unique spirocyclic lactam. Herein, we report an enantioselective total synthesis and biological evaluation of sanglifehrin A and B and analogs. Access to the spirocyclic lactam was achieved through convergent assembly of a key pyranone intermediate followed by a stereo-controlled spirocyclization. Read More

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Cyclophilin A Inhibits Human Respiratory Syncytial Virus (RSV) Replication by Binding to RSV-N through Its PPIase Activity.

J Virol 2021 Jul 12;95(15):e0056321. Epub 2021 Jul 12.

Department of Immunology, Hebei Medical University, Shijiazhuang, Hebei, China.

Human respiratory syncytial virus (hRSV) is the most common pathogen which causes acute lower respiratory infection (ALRI) in infants. Recently, virus-host interaction has become a hot spot of virus-related research, and it needs to be further elaborated for RSV infection. In this study, we found that RSV infection significantly increased the expression of cyclophilin A (cypA) in clinical patients, mice, and epithelial cells. Read More

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Induction of cyclophilin A by influenza A virus infection facilitates group A Streptococcus coinfection.

Cell Rep 2021 May;35(7):109159

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

During influenza A epidemics, bacterial coinfection is a major cause of increased morbidity and mortality. However, the roles of host factors in regulating influenza A virus (IAV)-triggered bacterial coinfection remain elusive. Cyclophilin A (CypA) is an important regulator of infection and immunity. Read More

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Porphyromonas gingivalis lipopolysaccharide and gingival fibroblast augment MMP-9 expression of monocytic U937 cells through cyclophilin A.

J Periodontol 2021 May 17. Epub 2021 May 17.

School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan.

Background: Intercellular cross-talking was suggested in matrix metalloproteinase (MMP)-9 expression with unknown mechanisms. Studies showed cyclophilin A (CypA) playing an important role in regulating MMP-9 expression in varied diseases. The aim of the study was to examine the CyPA on the MMP-9 augmentation in monocytic U937 cells after Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS) treatment and human gingival fibroblast (hGF) co-culture. Read More

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Cyclophilin A Plays Potential Roles in a Rat Model of Asthma and Suppression of Immune Response.

J Asthma Allergy 2021 7;14:471-480. Epub 2021 May 7.

Shanghai Research Institute of Acupuncture and Meridian, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.

Purpose: Cyclophilin A (CypA) inhibits CD4 T cell signal transduction via interleukin-2-inducible T-cell kinase (Itk), a tyrosine kinase required for T helper (Th) 2 cells function. Furthermore, mice with CypA silencing developed allergic diseases associated with increased Th2 cytokines production. CD4 T cells with a Th2-cytokine pattern have been demonstrated to have a pivotal role in the pathogenesis of asthma. Read More

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Cyclophilin A regulates secretion of tumour-derived extracellular vesicles.

Transl Oncol 2021 Aug 10;14(8):101112. Epub 2021 May 10.

UCD School of Biomolecular & Biomedical Science, Conway Institute, University College Dublin (UCD), Belfield, Dublin 4, Ireland. Electronic address:

Extracellular Vesicles (EVs) are a heterogenous population of particles that play an important role in cell-cell communication in physiological and pathophysiological situations. In this study we reveal that the peptidyl prolyl isomerase Cyclophilin A (CypA) is enriched in cancer-derived EVs from a range of haematopoietic malignancies. CypA-enriched blood cancer EVs were taken up by normal monocytes independent of EV surface trypsin-sensitive proteins and potently stimulated pro-inflammatory MMP9 and IL-6 secretion. Read More

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Relationship between Brain Tissue Changes and Blood Biomarkers of Cyclophilin A, Heme Oxygenase-1, and Inositol-Requiring Enzyme 1 in Patients with Alzheimer's Disease.

Diagnostics (Basel) 2021 Apr 21;11(5). Epub 2021 Apr 21.

Department of Radiology, Kyung Hee University Hospital at Gangdong, 892 Dongnam-ro, Gangdong-Gu, Seoul 05278, Korea.

Cyclophilin A (CypA), heme oxygenase-1 (HO-1), and inositol-requiring enzyme 1 (IRE1) are believed to be associated with Alzheimer's disease (AD). In this study, we investigated the association between gray matter volume (GMV) changes and blood levels of CypA, HO-1, and IRE1 in cognitively normal (CN) subjects and those with amnestic mild cognitive impairment (aMCI) and AD. Forty-five elderly CN, 34 aMCI, and 39 AD subjects were enrolled in this study. Read More

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DNase II mediates a parthanatos-like developmental cell death pathway in Drosophila primordial germ cells.

Nat Commun 2021 04 16;12(1):2285. Epub 2021 Apr 16.

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel.

During Drosophila embryonic development, cell death eliminates 30% of the primordial germ cells (PGCs). Inhibiting apoptosis does not prevent PGC death, suggesting a divergence from the conventional apoptotic program. Here, we demonstrate that PGCs normally activate an intrinsic alternative cell death (ACD) pathway mediated by DNase II release from lysosomes, leading to nuclear translocation and subsequent DNA double-strand breaks (DSBs). Read More

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Cyclophilins A, B, and C Role in Human T Lymphocytes Upon Inflammatory Conditions.

Front Immunol 2021 30;12:609196. Epub 2021 Mar 30.

Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, Spain.

Cyclophilins (Cyps) are a group of peptidyl-prolyl isomerases that play crucial roles in regulatory mechanisms of cellular physiology and pathology in several inflammatory conditions. Their receptor, CD147, also participates in the development and progression of the inflammatory response. Nevertheless, the main function of Cyps and their receptor are yet to be deciphered. Read More

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Levels of S100 calcium binding protein B (S100B), neuron-specific enolase (NSE), and cyclophilin A (CypA) in the serum of patients with severe craniocerebral injury and multiple injuries combined with delirium transferred from the ICU and their prognostic value.

Ann Palliat Med 2021 Mar;10(3):3371-3378

Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China; Department of anesthesia operation center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

Background: To analyze the levels of S100 calcium binding protein B (S100B), neuron-specific enolase (NSE), and cyclophilin A (CypA) in the serum of patients with severe craniocerebral injury combined with delirium and multiple injuries transferred from the intensive care unit (ICU), and their prognostic value.

Methods: The data of 98 patients with severe craniocerebral injury combined with delirium and multiple injuries admitted to our hospital from January 2018 to May 2019 were retrospectively analyzed as the study group. The differences in serum S100B, NSE, and CypA levels in each group were compared, and the deaths of the study group during follow-up were counted. Read More

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[Expression of cyclophilin A in oral squamous cell carcinoma and its effect on cell proliferation and invasion].

Hua Xi Kou Qiang Yi Xue Za Zhi 2021 Apr;39(2):164-169

Dept. of Stomatology, Wuhan University People,s Hospital, Wuhan 430060, China.

Objectives: To investigate the expression of cyclophilin A (CyPA) in oral squamous cell carcinoma (OSCC) and explore the effect of downregulating the expression of CyPA gene on the proliferation and invasion of SCC-25 cells.

Methods: A total of 77 cases of patients with OSCC were selected. The expression levels of CyPA proteins in OSCC and adjacent normal tissues were evaluated. Read More

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Ivabradine Induces Cardiac Protection against Myocardial Infarction by Preventing Cyclophilin-A Secretion in Pigs under Coronary Ischemia/Reperfusion.

Int J Mol Sci 2021 Mar 12;22(6). Epub 2021 Mar 12.

Hospital Ramón y Cajal Research Unit (IRYCIS), Cardiology Department, Universidad Francisco de Vitoria, 28223 Madrid, Spain.

In response to cardiac ischemia/reperfusion, proteolysis mediated by extracellular matrix metalloproteinase inducer (EMMPRIN) and its secreted ligand cyclophilin-A (CyPA) significantly contributes to cardiac injury and necrosis. Here, we aimed to investigate if, in addition to the effect on the funny current (I(f)), Ivabradine may also play a role against cardiac necrosis by reducing EMMPRIN/CyPA-mediated cardiac inflammation. In a porcine model of cardiac ischemia/reperfusion (IR), we found that administration of 0. Read More

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Identification of Cyclophilin A as a Potential Anticancer Target of Novel Nargenicin A1 Analog in AGS Gastric Cancer Cells.

Int J Mol Sci 2021 Mar 1;22(5). Epub 2021 Mar 1.

Department of Life Science and Biochemical Engineering, Sun Moon University, Asan 31460, Korea.

We recently discovered a novel nargenicin A1 analog, 23-demethyl 8,13-deoxynargenicin (compound 9), with potential anti-cancer and anti-angiogenic activities against human gastric adenocarcinoma (AGS) cells. To identify the key molecular targets of compound 9, that are responsible for its biological activities, the changes in proteome expression in AGS cells following compound 9 treatment were analyzed using two-dimensional gel electrophoresis (2-DE), followed by MALDI/TOF/MS. Analyses using chemical proteomics and western blotting revealed that compound 9 treatment significantly suppressed the expression of cyclophilin A (CypA), a member of the immunophilin family. Read More

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Cytoplasmic CPSF6 Regulates HIV-1 Capsid Trafficking and Infection in a Cyclophilin A-Dependent Manner.

mBio 2021 03 23;12(2). Epub 2021 Mar 23.

Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

Human immunodeficiency virus type 1 (HIV-1) capsid binds host proteins during infection, including cleavage and polyadenylation specificity factor 6 (CPSF6) and cyclophilin A (CypA). We observe that HIV-1 infection induces higher-order CPSF6 formation, and capsid-CPSF6 complexes cotraffic on microtubules. CPSF6-capsid complex trafficking is impacted by capsid alterations that reduce CPSF6 binding or by excess cytoplasmic CPSF6 expression, both of which are associated with decreased HIV-1 infection. Read More

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Cyclophilin A is an endogenous ligand for the triggering receptor expressed on myeloid cells-2 (TREM2).

FASEB J 2021 04;35(4):e21479

School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.

Triggering receptor expressed on myeloid cells 2 (TREM2) is a cell surface receptor expressed on macrophages, microglial cells, and pre-osteoclasts, and that participates in diverse cellular function, including inflammation, bone homeostasis, neurological development, and coagulation. In spite of the indispensable role of the TREM2 protein in the maintenance of immune homeostasis and osteoclast differentiation, the exact ligand for TREM2 has not yet been identified. Here, we report a putative TREM2 ligand which is secreted from MC38 cells and identified as a cyclophilin A (CypA). Read More

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Urinary Cyclophilin A as Marker of Tubular Cell Death and Kidney Injury.

Biomedicines 2021 Feb 20;9(2). Epub 2021 Feb 20.

Research Institute-Fundación Jiménez Díaz, Autonoma University, 28040 Madrid, Spain.

Despite the term acute kidney injury (AKI), clinical biomarkers for AKI reflect function rather than injury and independent markers of injury are needed. Tubular cell death, including necroptotic cell death, is a key feature of AKI. Cyclophilin A (CypA) is an intracellular protein that has been reported to be released during necroptosis. Read More

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February 2021

Cyclophilin A is a factor of antitumor defense in the early stages of tumor development.

Int Immunopharmacol 2021 May 26;94:107470. Epub 2021 Feb 26.

Federal State Budgetary Institution "N.N. Blokhin National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation, Kashirskoe sh. 24, Moscow 115478, Russian Federation. Electronic address:

Cyclophilin A (CypA) is a pro-inflammatory factor with multiple immunomodulating effects. Here, we investigated the effects of recombinant human CypA (rhCypA) as a factor of antitumor host defense. Our results demonstrated that rhCypA dramatically inhibited the growth of murine transplantable tumors (mammary adenocarcinoma Ca755, melanoma B16, Lewis lung carcinoma (LLC), and cervical cancer CC-5). Read More

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Structural Flexibility of Cyclosporine A Is Mediated by Amide - Isomerization and the Chameleonic Roles of Calcium.

J Phys Chem B 2021 02 1;125(5):1378-1391. Epub 2021 Feb 1.

Department of Chemistry, University of Tennessee, Knoxville, Tennessee 37996, United States.

Falling outside of Lipinski's rule of five, macrocyclic drugs have accessed unique binding sites of their target receptors unreachable by traditional small molecules. Cyclosporin(e) A (CycA), an extensively studied macrocyclic natural product, is an immunosuppressant with undesirable side effects such as electrolytic imbalances. In this work, a comprehensive view on the conformational landscape of CycA, its interactions with Ca, and host-guest interactions with cyclophilin A (CypA) is reported through exhaustive analyses that combine ion-mobility spectrometry-mass spectrometry (IMS-MS), nuclear magnetic resonance (NMR) spectroscopy, distance-geometry modeling, and NMR-driven molecular dynamics. Read More

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February 2021

Cyclophilin A: a key player for etiological agent infection.

Appl Microbiol Biotechnol 2021 Feb 25;105(4):1365-1377. Epub 2021 Jan 25.

Institute of Pathogenic Biology, Hengyang Medical College, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, No. 28, West Changsheng Road, Hengyang City, 421001, Hunan Province, People's Republic of China.

Cyclophilin A (CypA), a key member of the immunophilin family, is the most abundantly expressed isozyme of the 18 known human cyclophilins. Besides acting as an intracellular receptor for cyclosporine A, CypA plays a vital role in microorganismal infections, cardiovascular diseases, liver diseases, kidney diseases, neurodegeneration, cancer, rheumatoid arthritis, periodontitis, sepsis, asthma, and aging. This review focuses on the pivotal roles of CypA in the infection of etiological agents, which manifests mainly in promoting or inhibiting viral replication based on the host cell type and viral species. Read More

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February 2021

Identification of Celastrol as a Novel Therapeutic Agent for Pulmonary Arterial Hypertension and Right Ventricular Failure Through Suppression of Bsg (Basigin)/CyPA (Cyclophilin A).

Arterioscler Thromb Vasc Biol 2021 03 21;41(3):1205-1217. Epub 2021 Jan 21.

Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

Objective: Pulmonary arterial hypertension is characterized by abnormal proliferation of pulmonary artery smooth muscle cells and vascular remodeling, which leads to right ventricular (RV) failure. Bsg (Basigin) is a transmembrane glycoprotein that promotes myofibroblast differentiation, cell proliferation, and matrix metalloproteinase activation. CyPA (cyclophilin A) binds to its receptor Bsg and promotes pulmonary artery smooth muscle cell proliferation and inflammatory cell recruitment. Read More

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Maedi-visna virus Vif protein uses motifs distinct from HIV-1 Vif to bind zinc and the cofactor required for A3 degradation.

J Biol Chem 2021 Jan-Jun;296:100045. Epub 2020 Nov 24.

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA. Electronic address:

The mammalian apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3 or A3) family of cytidine deaminases restrict viral infections by mutating viral DNA and impeding reverse transcription. To overcome this antiviral activity, most lentiviruses express a viral accessory protein called the virion infectivity factor (Vif), which recruits A3 proteins to cullin-RING E3 ubiquitin ligases such as cullin-5 (Cul5) for ubiquitylation and subsequent proteasomal degradation. Although Vif proteins from primate lentiviruses such as HIV-1 utilize the transcription factor core-binding factor subunit beta as a noncanonical cofactor to stabilize the complex, the maedi-visna virus (MVV) Vif hijacks cyclophilin A (CypA) instead. Read More

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November 2020

Cyclophilin A inhibits A549 cell oxidative stress and apoptosis by modulating the PI3K/Akt/mTOR signaling pathway.

Biosci Rep 2021 01;41(1)

College of Life Sciences, Henan Agricultural University, Zhengzhou 450002, China.

The excessive and inappropriate production of reactive oxygen species (ROS) can cause oxidative stress and is implicated in the pathogenesis of lung cancer. Cyclophilin A (CypA), a member of the immunophilin family, is secreted in response to ROS. To determine the role of CypA in oxidative stress injury, we investigated the role that CypA plays in human lung carcinoma (A549) cells. Read More

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January 2021