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https://www.readbyqxmd.com/read/28197079/sirt3-in-neural-stem-cells-attenuates-microglia-activation-induced-oxidative-stress-injury-through-mitochondrial-pathway
#1
De-Qi Jiang, Yan Wang, Ming-Xing Li, Yan-Jiao Ma, Yong Wang
Sirtuin 3 (SIRT3), a mitochondrial protein, is involved in energy metabolism, cell apoptosis and mitochondrial function. However, the role of SIRT3 in neural stem cells (NSCs) remains unknown. In previous studies, we found that microglia activation-induced cytotoxicity negatively regulated survival of NSCs, along with mitochondrial dysfunction. The aim of this study was to investigate the potential neuroprotective effects of SIRT3 on the microglia activation-induced oxidative stress injury in NSCs and its possible mechanisms...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28187451/gsk1059615-kills-head-and-neck-squamous-cell-carcinoma-cells-possibly-via-activating-mitochondrial-programmed-necrosis-pathway
#2
Jing Xie, Quan Li, Xi Ding, Yunyun Gao
This study tested the anti-head and neck squamous cell carcinoma (HNSCC) cell activity by GSK1059615, a novel PI3K and mTOR dual inhibitor. GSK1059615 inhibited survival and proliferation of established (SCC-9, SQ20B and A253 lines) and primary human HNSCC cells. GSK1059615 blocked PI3K-AKT-mTOR activation in HNSCC cells. Intriguingly, GSK1059615 treatment in HNSCC cells failed to provoke apoptosis, but induced programmed necrosis. The latter was tested by mitochondria depolarization, ANT-1-cyclophilin-D mitochondrial association and lactate dehydrogenase (LDH) release...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28179991/a-homolog-of-cyclophilin-d-is-expressed-in-trypanosoma-cruzi-and-is-involved-in-the-oxidative-stress-damage-response
#3
Patricia L Bustos, Bibiana J Volta, Alina E Perrone, Natalia Milduberger, Jacqueline Bua
Mitochondria have an important role in energy production, homeostasis and cell death. The opening of the mitochondrial permeability transition pore (mPTP) is considered one of the key events in apoptosis and necrosis, modulated by cyclophilin D (CyPD), a crucial component of this protein complex. In Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, we have previously described that mitochondrial permeability transition occurs after oxidative stress induction in a cyclosporin A-dependent manner, a well-known cyclophilin inhibitor...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28174681/participation-of-3-o-sulfated-heparan-sulfates-in-the-protection-of-macrophages-by-herpes-simplex-virus-1-glycoprotein-d-and-cyclophilin-b-against-apoptosis
#4
Maxime Delos, Charles Hellec, François Foulquier, Mathieu Carpentier, Fabrice Allain, Agnès Denys
Heparan sulfates (HS) are involved in numerous biological processes, which rely on their ability to interact with a large panel of proteins. Although the reaction of 3-O-sulfation can be catalysed by the largest family of HS sulfotransferases, very few mechanisms have been associated with this modification and to date, only glycoprotein D (gD) of herpes simplex virus-1 (HSV-1 gD) and cyclophilin B (CyPB) have been well-described as ligands for 3-O-sulfated HS. Here, we hypothesized that both ligands could induce the same responses via a mechanism dependent on 3-O-sulfated HS...
February 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28158898/4pba-strongly-attenuates-endoplasmic-reticulum-stress-fibrosis-and-mitochondrial-apoptosis-markers-in-cyclosporine-treated-human-gingival-fibroblasts
#5
Suresh Ranga Rao, Subbarayan Rajasekaran, Supraja Ajitkumar, Murugan Girija Dinesh
Cyclosporine induces overgrowth of human gingiva. Previously we have shown (i) cyclosporine - inducing ER stress in human gingival fibroblasts, (ii) increased matrix protein expression, and (iii) interference with mitochondrial pro- and anti - apoptotic factors. This study was undertaken to assess the effects of melatonin (an antioxidant), 4PBA (an ER stress inhibitor), and simvastatin on the expression of ER Stress markers, as well as on matrix and mitochondrial markers. Human gingival fibroblasts incubated with cyclosporine, or without melatonin/4PBA/statin...
February 3, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28153875/prognostic-impacts-of-plasma-levels-of-cyclophilin-a-in-patients-with-coronary-artery-disease
#6
Tomohiro Ohtsuki, Kimio Satoh, Junichi Omura, Nobuhiro Kikuchi, Taijyu Satoh, Ryo Kurosawa, Masamichi Nogi, Shinichiro Sunamura, Nobuhiro Yaoita, Tatsuo Aoki, Shunsuke Tatebe, Koichiro Sugimura, Jun Takahashi, Satoshi Miyata, Hiroaki Shimokawa
OBJECTIVE: Cyclophilin A (CyPA) is secreted from vascular smooth muscle cells, inflammatory cells, and activated platelets in response to oxidative stress. We have recently demonstrated that plasma CyPA level is a novel biomarker for diagnosing coronary artery disease. However, it remains to be elucidated whether plasma CyPA levels also have a prognostic impact in such patients. APPROACH AND RESULTS: In 511 consecutive patients undergoing diagnostic coronary angiography, we measured the plasma levels of CyPA, high-sensitivity C-reactive protein (hsCRP), and brain natriuretic peptide and evaluated their prognostic impacts during the follow-up (42 months, interquartile range: 25-55 months)...
February 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28152427/discovery-of-1-3-benzyloxy-pyridin-2-yl-3-2-piperazin-1-yl-ethyl-urea-a-new-modulator-for-amyloid-beta-induced-mitochondrial-dysfunction
#7
Ahmed Elkamhawy, Jung-Eun Park, Ahmed H E Hassan, Hyunhwa Ra, Ae Nim Pae, Jiyoun Lee, Beoung-Geon Park, Bongjin Moon, Hyun-Mee Park, Eun Joo Roh
Herein, we report a new series of aliphatic substituted pyridyl-urea small molecules synthesized as potential modulators for amyloid beta (Aβ) induced mitochondrial dysfunction. Their blocking activities against Aβ-induced mitochondrial permeability transition pore (mPTP) opening were evaluated by JC-1 assay which measures the change of mitochondrial membrane potential (ΔΨm). The inhibitory activity of sixteen compounds against Aβ-induced mPTP opening was superior or almost similar to that of the standard Cyclosporin A (CsA)...
December 29, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28141792/preventing-permeability-transition-pore-opening-increases-mitochondrial-maturation-myocyte-differentiation-and-cardiac-function-in-the-neonatal-mouse-heart
#8
Jayson V Lingan, Ryan E Alanzalon, George A Porter
BACKGROUND: In embryonic myocytes, closure of the mitochondrial permeability transition pore (PTP) drives mitochondrial maturation and cardiac myocyte differentiation. Since neonatal cardiac myocytes remain relatively immature, we hypothesized that inducing PTP closure at this age, by inhibiting the PTP regulator, cyclophilin D (CyPD), genetically or with Cyclosporin A (CsA) and NIM811, would increase cardiac function by increasing mitochondrial maturation and myocyte differentiation...
January 31, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28134789/mrpl10-and-tbp-are-suitable-reference-genes-for-peripheral-nerve-crush-injury
#9
Yaxian Wang, Qianqian Shan, Yali Meng, Jiacheng Pan, Sheng Yi
Peripheral nerve injury triggers the dysregulation of a large number of genes at multiple sites, including neurons, peripheral nerve stump, and the target organ. Housekeeping genes were frequently used as reference genes to normalize the expression values of target genes. Suitable selection of housekeeping genes that are stably expressed after nerve injury minimizes bias elicited by reference genes and thus helps to better and more sensitively reflect gene expression changes. However, many housekeeping genes have been used as reference genes without testing the expression patterns of themselves...
January 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28122357/activation-of-akt-by-sc79-protects-myocardiocytes-from-oxygen-and-glucose-deprivation-ogd-re-oxygenation
#10
Koulong Zheng, Qing Zhang, Gang Lin, Yefei Li, Zhenqiang Sheng, Jue Wang, Liang Chen, Hui-He Lu
SC79 is a novel Akt activator. The current study tested its potential effect against oxygen and glucose deprivation (OGD)/re-oxygenation-induced myocardial cell death. We showed that SC79 activated Akt and protected H9c2 myocardial cells and primary murine myocardiocytes from OGD/re-oxygenation. Reversely, Akt inhibitor MK-2206 or Akt1 shRNA knockdown almost completely abolished SC79-mediated myocardial cytoprotection. SC79 treatment in H9c2 cells inhibited OGD/re-oxygenation-induced programmed necrosis pathway, evidenced by mitochondrial depolarization and cyclophilin D-p53-ANT-1 (adenine nucleotide translocator 1) association...
January 21, 2017: Oncotarget
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
#11
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
#12
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
#13
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...
February 7, 2017: Structure
https://www.readbyqxmd.com/read/28079595/acetylated-cyclophilin-a-is-a-major-mediator-in-hypoxia-induced-autophagy-and-pulmonary-vascular-angiogenesis
#14
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
#15
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
#16
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-the-structural-simplification-of-sanglifehrin-a
#17
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 E 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...
February 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28074922/soybean-cyclophilin-gmcyp1-interacts-with-an-isoflavonoid-regulator-gmmyb176
#18
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
#19
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...
February 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28062572/updates-in-understanding-the-role-of-cyclophilin-a-in-leukocyte-chemotaxis
#20
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
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