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https://www.readbyqxmd.com/read/28442737/structural-and-biochemical-insights-of-cypa-and-aif-interaction
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28391416/serum-cyclophilin-a-correlates-with-increased-tissue-mmp-9-in-patients-with-ulcerative-colitis-but-not-with-crohn-s-disease
#9
Aleksandra Piechota-Polanczyk, Marcin Włodarczyk, Aleksandra Sobolewska-Włodarczyk, Mateusz Jonakowski, Andrzej Pilarczyk, Krystyna Stec-Michalska, Maria Wiśniewska-Jarosińska, Jakub Fichna
BACKGROUND: Cyclophilin A (CyPA) is an immunomodulatory protein, high expression of which correlates with poor outcome of patients with inflammatory diseases. However, its role in inflammatory bowel disease (IBD) has not been studied. AIM: This study analyzes the correlation between cyclophilin A, matrix metalloproteinase (MMP)-9, and tissue inhibitor of MMP (TIMP)/MMP-9 complexes in the inflamed and non-inflamed colon mucosa of UC and CD patients. METHODS: Serum and biopsy specimens from inflamed and non-inflamed colonic mucosa of 38 patients with IBD (19 with UC and 19 with CD) and 16 controls were included in our study...
April 8, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28387980/immune-balance-in-hepatitis-b-infection-present-and-future-therapies
#10
REVIEW
Ashish Kumar Vyas, Ankur Jindal, Syed Hissar, Gayatri Ramakrishna, Nirupama Trehanpati
Chronic hepatitis B virus (HBV) infection affects millions of people worldwide and about half a million people die every year. India represents the second largest pool of chronic HBV infections with an estimated 40 million chronically infected patients. Persistence or clearance of HBV infection mainly depends upon host immune responses. Chronically infected individuals remain in immune tolerant phase unless HBV flares and leads to development of chronic active hepatitis or acute on chronic liver failure. Strategies based on inhibition of viral replication (nucleoside analogues) or immune modulation (Interferons) as monotherapy, or in combination in sequential therapies, are currently being used globally for reducing HBV viral load and mediating HBsAg clearance...
April 7, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28385890/ziploc-ing-the-structure-2-0-endoplasmic-reticulum-resident-peptidyl-prolyl-isomerases-show-different-activities-toward-hydroxyproline
#11
Yoshihiro Ishikawa, Kazunori Mizuno, Hans Peter Bächinger
Extracellular matrix proteins are biosynthesized in the rough endoplasmic reticulum (rER), and the triple-helical protein collagen is the most abundant extracellular matrix component in the human body. Many enzymes, molecular chaperones, and post-translational modifiers facilitate collagen biosynthesis. Collagen contains a large number of proline residues, so the cis/trans isomerization of proline peptide bonds is the rate-limiting step during triple-helix formation. Accordingly, the rER-resident peptidyl prolyl cis/trans isomerases (PPIases) play an important role in the zipper-like triple-helix formation in collagen...
April 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28384284/correction-blockade-of-cyclophilin-d-rescues-dexamethasone-induced-oxidative-stress-in-gingival-tissue
#12
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0173270.].
2017: PloS One
https://www.readbyqxmd.com/read/28378042/mitochondrial-permeability-transition-in-cardiac-ischemia-reperfusion-whether-cyclophilin-d-is-a-viable-target-for-cardioprotection
#13
REVIEW
Sabzali Javadov, Sehwan Jang, Rebecca Parodi-Rullán, Zaza Khuchua, Andrey V Kuznetsov
Growing number of studies provide strong evidence that the mitochondrial permeability transition pore (PTP), a non-selective channel in the inner mitochondrial membrane, is involved in the pathogenesis of cardiac ischemia-reperfusion and can be targeted to attenuate reperfusion-induced damage to the myocardium. The molecular identity of the PTP remains unknown and cyclophilin D is the only protein commonly accepted as a major regulator of the PTP opening. Therefore, cyclophilin D is an attractive target for pharmacological or genetic therapies to reduce ischemia-reperfusion injury in various animal models and humans...
April 4, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28363167/emodin-targets-mitochondrial-cyclophilin-d-to-induce-apoptosis-in-hepg2-cells
#14
Ling Zhang, Dian He, Kun Li, Hongli Liu, Baitao Wang, Lifang Zheng, Jiazhong Li
Emodin has demonstrated potent anticancer activity in human hepatocarcinoma cells and animal models, however, the cellular targets of emodin have not been fully defined. Here we report that emodin induces the dysfunction of mitochondria and the apoptosis in HepG2 cells through an enrichment in mitochondria. Specifically, A mitochondrial matrix protein (cyclophilin D, CyPD) is involved in emodin-induced apoptosis, and the inhibitor of CyPD (cyclosporin A) could almost completely suppressing the apoptosis; Moreover, as the expression of CyPD could be effectively inhibited by antioxidant N-acetyl-l-cysteine and epidermal growth factor (the activator of ERK), reactive oxygen species and ERK might be involved in the relevant role of CyPD...
March 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28356935/melittin-inhibits-the-invasion-of-mcf-7-cells-by-downregulating-cd147-and-mmp-9-expression
#15
Jianjun Wang, Fengyu Li, Jiang Tan, Xuewei Peng, Lili Sun, Ping Wang, Shengnan Jia, Qingmiao Yu, Hongliang Huo, Hongyan Zhao
Tumor invasion and metastasis are the critical steps in determining the aggressive phenotype of human cancers. Melittin, a major component of bee venom, has been reported to induce apoptosis in several cancer cells. However, the mechanisms of melittin involvement in cancer invasion and metastasis remain unclear. Our previous study indicated that melittin inhibits cyclophilin A (CypA), a ubiquitously distributed peptidylprolyl cis-trans isomerase, in macrophage cells. In the present study, the Transwell assay results showed that melittin may downregulate the invasion level of MCF-7 cells in a dose-dependent manner...
February 2017: Oncology Letters
https://www.readbyqxmd.com/read/28351946/stress-induced-dynamic-regulation-of-mitochondrial-stat3-and-its-association-with-cyclophilin-d-reduce-mitochondrial-ros-production
#16
Jeremy A Meier, Moonjung Hyun, Marc Cantwell, Ali Raza, Claudia Mertens, Vidisha Raje, Jennifer Sisler, Erin Tracy, Sylvia Torres-Odio, Suzana Gispert, Peter E Shaw, Heinz Baumann, Dipankar Bandyopadhyay, Kazuaki Takabe, Andrew C Larner
Signal transducer and activator of transcription 3 (STAT3) is associated with various physiological and pathological functions, mainly as a transcription factor that translocates to the nucleus upon tyrosine phosphorylation induced by cytokine stimulation. In addition, a small pool of STAT3 resides in the mitochondria, where it serves as a sensor for various metabolic stressors including reactive oxygen species (ROS). Mitochondrially localized STAT3 largely exerts its effects through direct or indirect regulation of the activity of the electron transport chain (ETC)...
March 28, 2017: Science Signaling
https://www.readbyqxmd.com/read/28345672/cyclophilins-and-nucleoporins-are-required-for-infection-mediated-by-capsids-from-circulating-hiv-2-primary-isolates
#17
João I Mamede, Florence Damond, Ariel de Bernardo, Sophie Matheron, Diane Descamps, Jean-Luc Battini, Marc Sitbon, Valérie Courgnaud
HIV-2 groups have emerged from sooty mangabey SIV and entered the human population in Africa on several separate occasions. Compared to world pandemic HIV-1 that arose from the chimpanzee SIVcpz virus, the SIVsm-derived HIV-2, largely confined to West Africa, is less replicative, less transmissible and less pathogenic. Here, we evaluated the interactions between host cellular factors, which control HIV-1 infection and target the capsid, and HIV-2 capsids obtained from primary isolates from patients with different disease progression status...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28339017/sirt1-is-required-for-mitochondrial-biogenesis-reprogramming-in-hypoxic-human-pulmonary-arteriolar-smooth-muscle-cells
#18
Pengyun Li, Yan Liu, Nana Burns, Ke-Seng Zhao, Rui Song
Although recent studies have reported that mitochondria are putative oxygen sensors underlying hypoxic pulmonary vasoconstriction, little is known concerning the sirtuin 1 (SIRT1)-mediated mitochondrial biogenesis regulatory program in pulmonary arteriolar smooth muscle cells (PASMCs) during hypoxia/reoxygenation (H/R). We investigated the epigenetic regulatory mechanism of mitochondrial biogenesis and function in human PASMCs during H/R. Human PASMCs were exposed to hypoxia of 24-48 h and reoxygenation of 24-48 h...
May 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28328748/cyclophilin-d-modulates-the-cardiac-mitochondrial-target-of-isoflurane-sevoflurane-and-desflurane
#19
Rania Harisseh, Pascal Chiari, Camille Villedieu, Pauline Sueur, Maryline Abrial, Jean-Luc Fellahi, Michel Ovize, Abdallah Gharib
BACKGROUND: Volatile anesthetics are known to limit myocardial ischemia-reperfusion injuries. Mitochondria were shown to be major contributors to cardioprotection. Cyclophilin D (CypD) is one of the main regulators of mitochondria-induced cell death. We compared the effect of isoflurane, sevoflurane and desflurane in the presence or absence of CypD, to clarify its role in the mechanism of cardioprotection induced by these anesthetics. METHODS: Oxidative phosphorylation, mitochondrial membrane potential and H2O2 production were measured in isolated mitochondria from wild-type or CypD knockout mice in basal conditions and after hypoxia-reoxygenation in presence or absence of volatiles anesthetics...
March 17, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28326644/hiv-1-susceptibility-of-transgenic-rat-derived-primary-macrophage-t-cells-and-a-t-cell-line-that-express-human-receptors-cyclint1-and-crm1-genes
#20
Hisatoshi Shida, Hiroyuki Okada, Hajime Suzuki, Xianfeng Zhang, Jing Chen, Yasuko Tsunetsugu-Yokota, Yuetsu Tanaka, Fumika Yakushiji, Yoshio Hayashi
We developed transgenic (Tg) rats that express human CD4, CCR5, CXCR4, CyclinT1, and CRM1 genes. Tg rat macrophages were efficiently infected with HIV-1 and supported production of infectious progeny virus. By contrast, both rat primary CD4(+) T cells and established T cell lines expressing human CD4, CCR5, CyclinT1, and CRM1 genes were infected inefficiently, but this was ameliorated by inhibition of cyclophilin A. The infectivity of rat T cell-derived virus was lower than that of human T cell-derived virus...
March 22, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
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