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https://www.readbyqxmd.com/read/29782963/bet-inhibition-by-jq1-alleviates-streptozotocin-induced-diabetic-cardiomyopathy
#1
Miao Guo, Hong-Xia Wang, Wen-Jun Chen
Diabetic cardiomyopathy is a cascade of complex events leading to eventual heart failure in diabetes. JQ1, one of Bromodomain and extra-terminal domain (BET) protein inhibitors, has exerted therapeutic effects on cancer proliferation, inflammation and cardiovascular disease. Recently, JQ1 was reported to protect mice from bleomycin-induced lung fibrosis and reverse the fibrotic response in carbon tetrachloride-induced liver fibrosis. However, its role in diabetic cardiomyopathy remains to be clarified. Our results indicated that JQ1 treatment suppressed cardiac fibrosis and improved cardiac function in a STZ-induced diabetic mouse model...
May 18, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29769046/%C3%AE-tocotrienol-induces-apoptosis-in-pancreatic-cancer-cells-by-upregulation-of-ceramide-synthesis-and-modulation-of-sphingolipid-transport
#2
Victoria E Palau, Kanishka Chakraborty, Daniel Wann, Janet Lightner, Keely Hilton, Marianne Brannon, William Stone, Koyamangalath Krishnan
BACKGROUND: Ceramide synthesis and metabolism is a promising target in cancer drug development. γ-tocotrienol (GT3), a member of the vitamin E family, orchestrates multiple effects that ensure the induction of apoptosis in both, wild-type and RAS-mutated pancreatic cancer cells. Here, we investigated whether these effects involve changes in ceramide synthesis and transport. METHODS: The effects of GT3 on the synthesis of ceramide via the de novo pathway, and the hydrolysis of sphingomyelin were analyzed by the expression levels of the enzymes serine palmitoyl transferase, ceramide synthase-6, and dihydroceramide desaturase, and acid sphingomyelinase in wild-type RAS BxPC3, and RAS-mutated MIA PaCa-2 and Panc 1 pancreatic cancer cells...
May 16, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29768434/plasma-membrane-insertion-of-kca2-3-sk3-is-dependent-upon-the-snare-proteins-syntaxin-4-and-snap23
#3
Claudia A Bertuccio, Tony T Wang, Kirk L Hamilton, Diego J Rodriguez-Gil, Steven B Condliffe, Daniel C Devor
We previously demonstrated endocytosis of KCa2.3 is caveolin-1-, dynamin II- and Rab5-dependent. KCa2.3 then enters Rab35/EPI64C- and RME-1-containing recycling endosomes and is returned to the plasma membrane (PM). Herein, we report on the mechanism by which KCa2.3 is inserted into the PM during recycling and following exit from the Golgi. We demonstrate KCa2.3 colocalizes with SNAP-23 and Syntaxin-4 in the PM of HEK and endothelial cells by confocal immunofluorescence microscopy. We further show KCa2.3 can be co-immunoprecipitated with SNAP-23 and Syntaxin-4...
2018: PloS One
https://www.readbyqxmd.com/read/29762069/a-common-variation-in-the-caveolin-1-gene-is-associated-with-high-serum-triglycerides-and-metabolic-syndrome-in-an-admixed-latin-american-population
#4
Gustavo Mora-García, Doris Gómez-Camargo, Ángelo Alario, Claudio Gómez-Alegría
BACKGROUND: The caveolin 1 (CAV1) gene has been associated with metabolic traits in animal models and human cohorts. Recently, a prevalent variant in CAV1 has been found to be related to metabolic syndrome in Hispanics living in North America. Since Hispanics represent an admixed population at high risk for cardiovascular diseases, in this study a Latin American population with a similar genetic background was assessed. OBJECTIVE: To analyze a genetic association between CAV1 and metabolic traits in an admixed Latin American population...
May 15, 2018: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/29761970/-caveolin-1-in-relation-with-mitochondria-and-cancer-metabolism-a-promising-target-for-cancer-therapy
#5
REVIEW
Ying Jiang, Shun Li, Hong Yang, Chunhui Wu, Yiyao Liu
To aggressively proliferate and metastasize, cancer cells are in extreme need of energy supply and nutrients. Therefore, a promising cancer therapy strategy is developed to target its hallmark feature of metabolism. Recent findings revealed the regulatory role of caveolin-1 (Cav-1), a structural protein of caveolae, in cancer metabolism. And low Cav-1 expression in tumor stroma was proved to be a central player of cancer malignant phenotype. Here, we summarized the progressions of studies on Cav-1, mitochondria and cancer metabolism to indicate that the altered metabolism induced by Cav-1 and mitochondria association is a major cause of cancer malignant phenotype...
October 1, 2017: Sheng Wu Yi Xue Gong Cheng Xue za Zhi, Journal of Biomedical Engineering, Shengwu Yixue Gongchengxue Zazhi
https://www.readbyqxmd.com/read/29760450/caveolin-3-differentially-orchestrates-cholinergic-and-serotonergic-constriction-of-murine-airways
#6
M Keshavarz, M Skill, M I Hollenhorst, S Maxeiner, M Walecki, U Pfeil, W Kummer, G Krasteva-Christ
The mechanisms of controlling airway smooth muscle (ASM) tone are of utmost clinical importance as inappropriate constriction is a hallmark in asthma and chronic obstructive pulmonary disease. Receptors for acetylcholine and serotonin, two relevant mediators in this context, appear to be incorporated in specialized, cholesterol-rich domains of the plasma membrane, termed caveolae due to their invaginated shape. The structural protein caveolin-1 partly accounts for anchoring of these receptors. We here determined the role of the other major caveolar protein, caveolin-3 (cav-3), in orchestrating cholinergic and serotonergic ASM responses, utilizing newly generated cav-3 deficient mice...
May 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29760379/autophagic-degradation-of-caveolin-1-promotes-liver-sinusoidal-endothelial-cells-defenestration
#7
Xiaoying Luo, Dan Wang, Xintao Zhu, Guozhen Wang, Yuehua You, Zuowei Ning, Yang Li, Siyi Jin, Yun Huang, Ye Hu, Tingting Chen, Ying Meng, Xu Li
Autophagy, interacting with actin cytoskeleton and the NO-dependent pathway, may affect the phenotype and function of endothelial cells. Moreover, caveolin-1 (Cav-1), as a structure protein in liver sinusoidal endothelial cells (LSECs), is closely related to autophagy. Hence, we aim to explore the role of autophagic degradation of Cav-1 in LSECs defenestration. In vivo, we found the increase of autophagy in liver sinusoidal endothelium in human fibrotic liver. Furthermore, autophagy, degradation of Cav-1, and actin filament (F-actin) remodeling were triggered during the process of CCl4-induced LSECs defenestration; in contrast, autophagy inhibitor 3MA diminished the degradation of Cav-1 to maintain fenestrae and relieve CCl4-induced fibrosis...
May 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29753904/sorbitan-ester-nanoparticles-sens-as-a-novel-topical-ocular-drug-delivery-system-design-optimization-and-in-vitro-ex-vivo-evaluation
#8
Jesus Alvarez-Trabado, Antonio López-García, Manuel Martín-Pastor, Yolanda Diebold, Alejandro Sanchez
We explored the potential of two types of sorbitan ester nanoparticles (SENS) as novel tools for topical ocular drug delivery. The optimized SENS formulation (SENS-OPT) consisted of nanoparticles (NPs) of 170.5 nm, zeta potential +33.9 mV, and cyclosporine loading of 19.66%. After hyaluronic acid (HA) coating, the resulting SENS-OPT-HA NPs had a particle size of 177.6 nm and zeta potential of -20.6 mV. The NPs were stable during 3 months of storage at different temperatures and did not aggregate in the presence of protein-enriched simulated lacrimal fluid...
May 10, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29752441/ptbp3-contributes-to-the-metastasis-of-gastric-cancer-by-mediating-cav1-alternative-splicing
#9
Xin Liang, Weixia Chen, Haiyang Shi, Xiangyu Gu, Yueqi Li, Yingxue Qi, Ke Xu, Aiguang Zhao, Jianwen Liu
Polypyrimidine tract-binding protein 3 (PTBP3) is an essential RNA-binding protein with roles in RNA splicing, 3' end processing and translation. Although increasing evidence implicates PTBP3 in several cancers, its role in gastric cancer metastasis remains poorly explored. In this study, we found that PTBP3 was upregulated in the gastric cancer tissues of patients with lymph node metastasis. Patients with high PTBP3 expression levels had significantly shorter survival than those with low PTBP3 expression. Overexpression/knockdown of PTBP3 expression had no effect on proliferation, whereas it regulated migration and invasion in vitro...
May 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29751779/essential-role-of-atp6ap2-enrichment-in-caveolae-lipid-raft-microdomains-for-the-induction-of-neuronal-differentiation-of-stem-cells
#10
Nehman Makdissy, Katia Haddad, Jeanne D'arc AlBacha, Diana Chaker, Bassel Ismail, Albert Azar, Ghada Oreibi, David Ayoub, Ibrahim Achkar, Didier Quilliot, Ziad Fajloun
BACKGROUND: The subcellular distribution of prorenin receptor and adaptor protein ATP6AP2 may affect neurogenesis. In this study, we hypothesized that ATP6AP2 expression and subcellular relocalization from caveolae/lipid raft microdomains (CLR-Ms) to intracellular sites may correlate with neuronal differentiation (Neu-Dif) of adipose-derived mesenchymal stem cells (ADSCs). METHODS: Human ADSCs isolated from 24 healthy donors and 24 patients with neurological disorders (ND) were cultured and induced for Neu-Dif...
May 11, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29746866/cav-1-promotes-atherosclerosis-by-activating-jnk-associated-signaling
#11
Dong-Xia Wang, Yong-Quan Pan, Bing Liu, Li Dai
The objective of the study is to calculate the role and underlying the molecular mechanisms of caveolin-1 (Cav-1) in atherosclerosis (AS). Cav-1 was mainly expressed in the endothelial cells of atherosclerotic lesions in both human patients and apolipoprotein E deficient (ApoE-/- ) mice. Cav-1 deficiency (Cav-1-/- ) attenuated high-fat diet (HFD)-induced atherosclerotic lesions in ApoE-/- mice, supported by the reduced aortic plaques. Cav-1-/- reduced the macrophage content and decreased the release of inflammation-related cytokines or chemokine in serum or abdominal aortas, accompanied with the inactivation of inhibitor κB kinase κ (IKKβ)/p65/IκBα signaling pathway...
May 7, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29746166/endothelial-barrier-function-is-differentially-regulated-by-ceacam1-mediated-signaling
#12
Sharang Ghavampour, Florian Kleefeldt, Heike Bömmel, Julian Volland, Alexander Paus, Andrea Horst, Verena Pfeiffer, Stefan Hübner, Nicole Wagner, Uwe Rueckschloss, Süleyman Ergün
Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) is known to be crucial to vasculogenesis and angiogenesis. Recently, CEACAM1 deficiency was shown to result in the formation of aortic plaque-like lesions, indicating a role for CEACAM1 in adult vessels as well. The underlying mechanisms remained largely elusive. Therefore, we aimed to elucidate the role of CEACAM1 in endothelial homeostasis. Here, we show that CEACAM1 deficiency causes subcellular eNOS redistribution in endothelial cells ( i...
May 10, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29741760/involvement-of-cgrp-rcp-in-the-caveolin-1-erk1-2-signal-pathway-in-the-static-pressure-induced-proliferation-of-vascular-smooth-muscle-cells
#13
Feng Guo, Li Yang, Jingfei Luo, Haiyan Quan, Zhen Wang, Hongyan Peng, Chenliang Hong, Jie Li, Zhisheng Jiang, Liang Zhang, Xuping Qin
Previous study suggested that the receptor component protein (RCP), one of the components of calcitonin gene-related peptide (CGRP) receptor, plays a multiple role in the cellular signal transduction. The study was designed to investigate whether or not the RCP involved in the regulation of caveolin-1/extracellular signal-regulated kinases-1 and -2 (ERK1/2) signal pathway in the vascular smooth muscle cells (VSMCs) proliferation induced by static pressure. Mouse-derived VSMCs line A10 (A10 VSMCs) was served as project in this experiment...
May 9, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29740099/early-events-during-human-coronavirus-oc43-entry-to-the-cell
#14
Katarzyna Owczarek, Artur Szczepanski, Aleksandra Milewska, Zbigniew Baster, Zenon Rajfur, Michal Sarna, Krzysztof Pyrc
The Coronaviridae family clusters a number of large RNA viruses, which share several structural and functional features. However, members of this family recognize different cellular receptors and exploit different entry routes, what affects their species specificity and virulence. The aim of this study was to determine how human coronavirus OC43 enters the susceptible cell. Using confocal microscopy and molecular biology tools we visualized early events during infection. We found that the virus employs caveolin-1 dependent endocytosis for the entry and the scission of virus-containing vesicles from the cell surface is dynamin-dependent...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29736213/taxifolin-attenuates-diabetic-nephropathy-in-streptozotocin-induced-diabetic-rats
#15
Yanling Zhao, Wenwen Huang, Jiali Wang, Yan Chen, Wen Huang, Yonglin Zhu
The current study evaluates the effects of taxifolin (TA) on streptozotocin (STZ)-induced diabetic nephropathy in rats. We performed oral glucose tolerance tests (OGTTs) to determine blood glucose levels. We also measured the following biochemical parameters: uric acid, creatinine, and serum insulin. Kidney pathology was examined by staining sections with hematoxylin-eosin (H&E). The expression of Caveolin-1 and NF-κB was analyzed by qRT-PCR and western blotting. TA significantly reduced the concentrations of blood glucose, uric acid, creatinine, and serum insulin in STZ-induced diabetic rats...
2018: American Journal of Translational Research
https://www.readbyqxmd.com/read/29736031/nuclear-pore-complex-mediated-modulation-of-tcr-signaling-is-required-for-na%C3%A3-ve-cd4-t-cell-homeostasis
#16
Joana Borlido, Stephen Sakuma, Marcela Raices, Florent Carrette, Roberto Tinoco, Linda M Bradley, Maximiliano A D'Angelo
Nuclear pore complexes (NPCs) are channels connecting the nucleus with the cytoplasm. We report that loss of the tissue-specific NPC component Nup210 causes a severe deficit of naïve CD4+ T cells. Nup210-deficient CD4+ T lymphocytes develop normally but fail to survive in the periphery. The decreased survival results from both an impaired ability to transmit tonic T cell receptor (TCR) signals and increased levels of Fas, which sensitize Nup210-/- naïve CD4+ T cells to Fas-mediated cell death. Mechanistically, Nup210 regulates these processes by modulating the expression of Cav2 (encoding Caveolin-2) and Jun at the nuclear periphery...
May 7, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29734378/correction-caveolin-3-promotes-glycometabolism-growth-and-proliferation-in-muscle-cells
#17
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0189004.].
2018: PloS One
https://www.readbyqxmd.com/read/29729269/ll-37-induced-human-osteoblast-cytotoxicity-and-permeability-occurs-independently-of-cellular-ll-37-uptake-through-clathrin-mediated-endocytosis
#18
Emma Anders, Sara Dahl, Daniel Svensson, Bengt-Olof Nilsson
The host defense peptide LL-37 is cytotoxic for bacteria but it has also been reported to reduce host cell viability through an intracellular mechanism. LL-37-evoked cytotoxicity may be involved in the loss of bone tissue in periodontitis which is an inflammatory disease characterized by high concentrations of LL-37 observed locally in the periodontal tissue at the inflammation process. Here, we showed that LL-37 reduced human osteoblast-like MG63 cell viability assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and increased plasma membrane permeability determined by measuring intracellular Ca2+ levels and lactate dehydrogenase (LDH) release...
May 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29728594/roles-of-galnac-disialyl-lactotetraosyl-antigens-in-renal-cancer-cells
#19
Akiko Tsuchida, Motohiro Senda, Akihiro Ito, Seiichi Saito, Makoto Kiso, Takayuki Ando, Anne Harduin-Lepers, Akio Matsuda, Keiko Furukawa, Koichi Furukawa
GalNAc-disialyl Lc4 (GalNAc-DSLc4) was reported as a novel antigen that associated with malignant features of renal cell cancers (RCCs). To clarify roles of GalNAc-DSLc4 in malignant properties of RCCs, we identified B4GalNAc-T2 as a responsible gene for the synthesis of GalNAc-DSLc4, and prepared stable transfectants of GalNAc-T2 cDNA using VMRC-RCW cells, resulting in the establishment of high expressants of GalNAc-DSLc4. They showed increased proliferation and invasion, and specific adhesion to laminin. In the transfectants, PI3K/Akt signals were highly activated by serum stimulation or adhesion to laminin...
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29716956/cell-free-formation-and-interactome-analysis-of-caveolae
#20
WooRam Jung, Emma Sierecki, Michele Bastiani, Ailis O'Carroll, Kirill Alexandrov, James Rae, Wayne Johnston, Dominic J B Hunter, Charles Ferguson, Yann Gambin, Nicholas Ariotti, Robert G Parton
Caveolae have been linked to the regulation of signaling pathways in eukaryotic cells through direct interactions with caveolins. Here, we describe a cell-free system based on Leishmania tarentolae ( Lt ) extracts for the biogenesis of caveolae and show its use for single-molecule interaction studies. Insertion of expressed caveolin-1 (CAV1) into Lt membranes was analogous to that of caveolin in native membranes. Electron tomography showed that caveolins generate domains of precise size and curvature. Cell-free caveolae were used in quantitative assays to test the interaction of membrane-inserted caveolin with signaling proteins and to determine the stoichiometry of interactions...
May 1, 2018: Journal of Cell Biology
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