scholarly journals Preparation, Characterization and Refolding in Vitro of a Recombinant Human Cyclophilin A Mutant: Effect of a Single Pro/Ser Substitution on Cyclophilin A Structure and Properties

2008 ◽  
Vol 24 (2) ◽  
pp. 302-310 ◽  
Author(s):  
L.-R. Xu ◽  
X. Yan ◽  
M. Luo ◽  
Y.-X. Guan ◽  
S.-J. Yao
Keyword(s):  
Cyclophilin A ◽  
Structure And Properties ◽  
Mutant Effect

scholarly journals Intravenous injection of cyclophilin A realizes the transient and reversible opening of barrier of neural vasculature through basigin in endothelial cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Narumi Nakada-Honda ◽  
Dan Cui ◽  
Satoshi Matsuda ◽  
Eiji Ikeda
Keyword(s):  
Endothelial Cells ◽  
Single Dose ◽  
Blood Brain Barrier ◽  
Intravenous Injection ◽  
Cyclophilin A ◽  
Brain Barrier ◽  
Blood Brain ◽  
Neural Tissues ◽  
Neural Diseases

AbstractNeural vasculature forms the blood–brain barrier against the delivery of systemically administered therapeutic drugs into parenchyma of neural tissues. Therefore, procedures to open the blood–brain barrier with minimal damage to tissues would lead to the great progress in therapeutic strategy for intractable neural diseases. In this study, through analyses with mouse in vitro brain microvascular endothelial cells and in vivo neural vasculature, we demonstrate that the administration of cyclophilin A (CypA), a ligand of basigin which is expressed in barrier-forming endothelial cells, realizes the artificial opening of blood–brain barrier. Monolayers of endothelial cells lost their barrier properties through the disappearance of claudin-5, an integral tight junction molecule, from cell membranes in a transient and reversible manner. Furthermore, the intravenous injection of a single dose of CypA into mice resulted in the opening of blood–brain barrier for a certain period which enabled the enhanced delivery of systemically administered doxorubicin into the parenchyma of neural tissues. These findings that the pre-injection of a single dose of CypA realizes an artificial, transient as well as reversible opening of blood–brain barrier are considered to be a great step toward the establishment of therapeutic protocols to overcome the intractability of neural diseases.

Evidence that intracellular cyclophilin A and cyclophilin A/CD147 receptor-mediated ERK1/2 signalling can protect neurons against in vitro oxidative and ischemic injury

2007 ◽  
Vol 25 (1) ◽  
pp. 54-64 ◽  
Author(s):  
Sherif Boulos ◽  
Bruno P. Meloni ◽  
Peter G. Arthur ◽  
Bernadette Majda ◽  
Christina Bojarski ◽  
...  
Keyword(s):  
Ischemic Injury ◽  
Cyclophilin A

scholarly journals Cyclophilin a as a Mediator of Tissue Injure and Nephrotoxicity

2012 ◽  
Vol 4 (2) ◽  
pp. 42-44
Author(s):  
Grace Moscoso-Solorzano ◽  
Gianna Mastroianni-Kirsztajn
Keyword(s):  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Cyclophilin A ◽  
Common Mechanism ◽  
Ppiase Activity ◽  
Expression Of Genes ◽  
Inflammatory Stimuli ◽  
Genes Encoding ◽  
Inflammatory Processes

Cyclophilin A (CypA) belongs to the peptidyl-prolil isomerase (PPlase) family of proteins and it is also known as the cellular receptor for cyclosporine A (CsA). CsA binds to CypA and inhibits the PPIase activity, but the CypA-CsA complex also binds to calcineurin that promotes the expression of genes encoding cytokines and other proteins required for immune response. In addition, the polymorphism variation of CypA promoter seems to have an influence on the expression of CypA in in vitro studies. CypA was also implicated in inflammatory processes (such as, among others, those observed in rheumatoid arthritis, atherosclerotic disease, nephrotoxicity) and it can be secreted by cells in response to inflammatory stimuli. CypA can also have a role in the molecular mechanisms by which CsA induces nephroxicity but these remain poorly understood. Recent studies suggest that CsA inhibition of CypA PPlase activity is a possible mechanism of this drug toxicity. In addition, CypA overexpression could be protective against CsA nephrotoxicity. Finally, the putative common mechanism by which CypA could be involved in CsA nephrotoxicity and tissue injury is related to its proinflammatory effects in cells.

In vitro studies on the structure and properties of silk fibroin aqueous solutions in silkworm

2013 ◽  
Vol 62 ◽  
pp. 162-166 ◽  
Author(s):  
Yuan Jin ◽  
Yichun Hang ◽  
Jie Luo ◽  
Yaopeng Zhang ◽  
Huili Shao ◽  
...  
Keyword(s):  
Aqueous Solutions ◽  
Silk Fibroin ◽  
In Vitro Studies ◽  
Structure And Properties

scholarly journals A New Method for in vitro Glycogen Synthesis, and the Structure and Properties of the Synthesized Glycogen

2010 ◽  
Vol 57 (2) ◽  
pp. 105-111 ◽  
Author(s):  
Hideki Kajiura ◽  
Hiroki Takata ◽  
Tsunehisa Akiyama ◽  
Reiko Ueyama ◽  
Ryo Kakutani ◽  
...  
Keyword(s):  
Glycogen Synthesis ◽  
New Method ◽  
Structure And Properties

scholarly journals Cyclophilin A plays an important role in embryo implantation through activating Stat3

Reproduction ◽  
2020 ◽  
Vol 160 (3) ◽  
pp. 343-351
Author(s):  
Tao Yu ◽  
Shuai Lin ◽  
Rui Xu ◽  
Tian-Xi Du ◽  
Yang Li ◽  
...  
Keyword(s):  
Embryo Implantation ◽  
Specific Inhibitor ◽  
Cyclophilin A ◽  
Cellular Functions ◽  
Ovariectomized Mice ◽  
Inflammatory Stimuli ◽  
Implantation Sites ◽  
Cypa Expression

Embryo implantation is a crucial step for the successful establishment of mammalian pregnancy. Cyclophilin A (CYPA) is a ubiquitously expressed intracellular protein and is secreted in response to inflammatory stimuli to regulate diverse cellular functions. However, there are currently no reports about the role of CYPA in embryo implantation. Here, we examine the expression pattern of CYPA during mouse early pregnancy and explore the potential role of CYPA during implantation. CYPA is expressed in the subluminal stroma surrounding the implanting blastocyst on day 5 of pregnancy, but not at inter-implantation sites. In ovariectomized mice, estrogen and progesterone significantly stimulate CYPA expression. When pregnant mice are injected intraperitoneally with CYPA inhibitor, the numbers of implantation sites are significantly reduced. Using an in vitro stromal cell culture system, Ppia siRNA knockdown of CYPA and CYPA-specific inhibitor treatment partially inhibits levels of CD147, MMP3 and MMP9. Decreased CYPA expression also significantly inhibits Stat3 activity and expands estrogen responsiveness. Taken together, CYPA may play an important role during mouse embryo implantation.

Abstract 518: Cyclophilin A is a Novel Pro-Inflammatory Cytokine that Accelerates Development of Atherosclerosis

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kimio Satoh ◽  
Michael R O’Dell ◽  
Duan-fang Liao ◽  
Zhaoqiang Cui ◽  
Patrizia Nigro ◽  
...  
Keyword(s):  
New York ◽  
Cell Migration ◽  
Rhode Island ◽  
Inflammatory Cytokine ◽  
Inflammatory Cell ◽  
Cyclophilin A ◽  
Heart Association ◽  
List Type ◽  
En Face

Background - Cyclophilin A (CyPA), a member of the immunophilin family, is highly expressed in vascular smooth muscle cells (VSMC) in mice and humans. CyPA is secreted in response to reactive oxygen species (ROS) and also is a positive regulator of helper T (Th) profile promoting differentiation of Th0 cells into Th1 lymphocytes (increased IFN-γ The development of atherosclerosis involves vascular inflammatory cytokine release, inflammatory cell migration/activation, and altered Th1/Th2 profile. Based on the role of CyPA in ROS signaling and Th profile we hypothesized that CyPA would promote atherosclerosis. Methods and Results - We compared atherosclerosis development in ApoE −/− and ApoE −/− CyPA −/− mice using two different models. In ApoE −/− mice fed a high-fat diet for 16 weeks, atherosclerosis assessed by oil-red O (ORO) staining was significantly greater in ApoE −/− mice compared to ApoE −/− CyPA −/− mice (%ORO, en face aorta; 23.1±5.5 vs. 6.8±3.2, P <0.01). Immunostaining of atherosclerotic lesions in the aortic cusp revealed the co-localization of CyPA, CD45, and MCP-1, suggesting the importance of CyPA for inflammatory cell recruitment and cytokine production. Angiotensin II infusion (AngII, 1000 ng/min/kg, 4 weeks) significantly increased atherosclerosis area in ApoE −/− mice, which was significantly less in ApoE −/− CyPA −/− mice (%ORO, en face aorta; 11.1±4.6 vs. 4.0±2.8, P<0.01). ApoE −/− mice showed significant increases in vascular MCP-1 expression, VCAM-1 expression, and inflammatory cell migration to the aortic wall, all of which were significantly less in ApoE −/− CyPA −/− mice. Cytokine/chemokine array analysis revealed that AngII significantly increased secretion of numerous cytokine/chemokines from ApoE −/− spleno-cytes, which was significantly less in ApoE −/− CyPA −/− splenocytes. Mechanistic studies in vitro revealed that AngII enhanced CyPA secretion from mouse aortic VSMC. Finally, expression of CyPA was significantly increased in atherosclerotic plaques of patients with acute coronary syndromes. Conclusion - CyPA is a novel mediator of atherosclerosis by promoting inflammatory cytokine/chemokine secretion, adhesion molecule expression, and inflammatory cell migration. This research has received full or partial funding support from the American Heart Association, AHA Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).

Leukocyte Adhesion and Activation in Atherothrombosis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. SCI-52-SCI-52
Author(s):  
Meinrad Gawaz
Keyword(s):  
Myocardial Infarction ◽  
Progenitor Cells ◽  
Myocardial Injury ◽  
Conflicts Of Interest ◽  
Vascular Inflammation ◽  
Dynamic Change ◽  
Cyclophilin A ◽  
Ppiase Activity ◽  
Monocyte Migration

Abstract Platelets interact with a variety of cells, including leukocytes and progenitor cells. Upon activation, platelets release chemokines such as CXCL12/SDF-1 that modulate important functional aspects of vascular inflammation and atherogenesis. Platelet-derived SDF-1 and CyPA regulate chemotaxis, migration, and cell activation in the microenvironment of accumulating platelets. Previously we have shown that platelets are the major source of CXCL12/SDF-1. Platelet-derived SDF-1 provides a strong signal for recruitment of circulating progenitor cells and leukocytes towards vascular and myocardial injury. Patients with severe coronary artery disease have enhanced levels of plasma and platelet-associated SDF-1 that correlates with an enhanced number of circulating progenitor cells and the development of cardiovascular diseases. In patients with both acute myocardial infarction platelet-SDF-1 and an increase in circulating platelet/progenitor cell aggregates, the combination is associated with myocardial recovery and improved prognosis, indicating that platelet-SDF-1 is critical for repair and regeneration of vascular or myocardial injury. Administration of a stable recombinant SDF-1 fusion protein reduces infarct size and preserves myocardial infarction in mice. We showed that platelet-derived SDF-1 is an important survival factor both for platelets (in an autocrine manner) and for surrounding cells. SDF-1 released from activated platelets binds to its receptor CXCR4 and induces internalization of the SDF-1/CXCR4 complex. SDF-1-ligation of CXCR4 augments surface expression of CXCR7; a process coupled via ERK1/2 and cyclophilin A. SDF-1α caused downstream phosphorylation of Erk1/2 and cyclophilin A (CyPA). NIM-811 a CyPA-PPIase-activity inhibitor significantly abolished SDF-1α-driven CXCR7 surface exposure. Moreover, Cypa-/-murine platelets failed to show SDF-1α/CXCR4-mediated CXCR7 translocation. SDF-1α-induced ubiquitination of CXCR7 was essential for its surface translocation and was dependent on Erk1/2 and CyPA-PPIase activity, inhibited by U0126 and NIM-811, respectively. In contrast to wild-type, Cypa-/- murine platelets failed to exhibit a dynamic change in CXCR7 ubiquitination status upon SDF-1α exposure and thus failed in subsequent CXCR7 externalization. SDF-1/CXR4-driven CXCR7 translocation inhibits activation-induced apoptosis of platelets and prolongs platelet survival in vitro and in vivo. Similarly, platelet SDF-1 interacts with monocytes, reduces apoptosis and promotes differentiation of monocytes into macrophages. Inhibition of platelet release and adhesion to endothelial cells reduces monocyte migration and differentiation into macrophages in vitro and attenuates vascular inflammation and atheroprogression in apoE-deficient mice. In conclusion, platelets and platelet interaction with leukocytes are critical in regulation of vascular inflammation and atheroprogression and may offer promising targets for modulating inflammation in disease states. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document