8 results on '"Cav-1, caveolin-1"'
Search Results
2. Membrane cholesterol regulates TRPV4 function, cytoskeletal expression, and the cellular response to tension
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David Križaj, Trine Lisberg Toft-Bertelsen, Michael H. Elliott, Nanna MacAulay, Paul S. Bernstein, Grace F. Hoffmann, Eric Enyong, Aruna Gorusupudi, Amy Lin, and Monika Lakk
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Male ,MβCD, m-β-cyclodextrin ,TM, trabecular meshwork ,ROI, region of interest ,Mechanotransduction, Cellular ,Biochemistry ,[Ca2+]i, intracellular calcium concentration ,TMCM, trabecular meshwork cell medium ,Xenopus laevis ,Transient receptor potential channel ,chemistry.chemical_compound ,Endocrinology ,Caveolae ,TRPV4, transient receptor potential vanilloid isoform 4 ,Mechanotransduction ,dyslipidemias ,Cytoskeleton ,Lipid raft ,Cells, Cultured ,lipid rafts ,Chemistry ,NA, numerical aperture ,Cav-1, caveolin-1 ,smooth muscle cells ,ECM, extracellular matrix ,Cell biology ,αSMA, α-smooth muscle actin ,Cholesterol ,medicine.anatomical_structure ,eye/retina ,lipids (amino acids, peptides, and proteins) ,Research Article ,TRPV4 ,HTS, hypotonic stimuli ,PBS, phosphate-buffered saline ,TRPV Cation Channels ,QD415-436 ,ir, immunoreactivity ,medicine ,cell signaling ,Animals ,Humans ,mechanotransduction ,Aged ,cyclodextrins ,Cell Membrane ,Cell Biology ,Actin cytoskeleton ,IOP, intraocular pressure ,F-actin, filamentous actin ,glaucoma ,Tonicity ,Trabecular meshwork ,Homeostasis ,C/PC, cholesterol/phosphatidylcholine - Abstract
Despite the association of cholesterol with debilitating pressure-related diseases such as glaucoma, heart disease, and diabetes, its role in mechanotransduction is not well understood. We investigated the relationship between mechanical strain, free membrane cholesterol, actin cytoskeleton, and the stretch-activated transient receptor potential vanilloid isoform 4 (TRPV4) channel in human trabecular meshwork (TM) cells. Physiological levels of cyclic stretch resulted in time-dependent decreases in membrane cholesterol/phosphatidylcholine ratio and upregulation of stress fibers. Depleting free membrane cholesterol with m-β-cyclodextrin (MβCD) augmented TRPV4 activation by the agonist GSK1016790A, swelling and strain, with the effects reversed by cholesterol supplementation. MβCD increased membrane expression of TRPV4, caveolin-1, and flotillin. TRPV4 did not colocalize or interact with caveolae or lipid rafts, apart from a truncated ∼75 kDa variant partially precipitated by a caveolin-1 antibody. MβCD induced currents in TRPV4-expressing Xenopus laevis oocytes. Thus, membrane cholesterol regulates trabecular transduction of mechanical information, with TRPV4 channels mainly located outside the cholesterol-enriched membrane domains. Moreover, the biomechanical milieu itself shapes the lipid content of TM membranes. Diet, cholesterol metabolism, and mechanical stress might modulate the conventional outflow pathway and intraocular pressure in glaucoma and diabetes in part by modulating TM mechanosensing., Graphical abstract more...
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- 2021
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Catalog
3. Polysaccharides from Panax ginseng promote intestinal epithelial cell migration through affecting the Ca 2+ related regulators.
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Zhu H, Cao J, Liang X, Luo M, Wang A, Hu L, and Li R
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Background and Aim: Panax ginseng , a key herbal medicine of replenishing Qi and tonifying Spleen, is widely used in the treatment of gastrointestinal diseases in East Asia. In this study, we aim to investigate the potential effects and mechanisms of polysaccharides from P. ginseng (PGP) on intestinal mucosal restitution which is one of the crucial repair modalities during the recovery of mucosal injury controlled by the Ca
2+ signaling., Methods: Rat model of intestinal mucosal injury was induced by indomethacin. The fractional cell migration was carried out by immunohistochemistry staining with BrdU. The morphological observations on intestinal mucosal injury were also performed. Intestinal epithelial cell (IEC-6) migration in vitro was conducted by scratch method. Western-blot was adopted to determine the expressions of PLC-γ1, Rac1, TRPC1, RhoA and Cav-1. Immunoprecipitation was used to evaluate the levels of Rac1/PLC-γ1, RhoA/TRPC1 and Cav-1/TRPC1., Results: The results showed that PGP effectively reduced the assessment of intestinal mucosal injury, reversed the inhibition of epithelial cell migration induced by Indomethacin, and increased the level of Ca2+ in intestinal mucosa in vivo. Moreover, PGP dramatically promoted IEC-6 cell migration, the expression of Ca2+ regulators (PLC-γ1, Rac1, TRPC1, Cav-1 and RhoA) as well as protein complexes (Rac1/PLC-γ1, Cav-1/TRPC1 and RhoA/TRPC1) in vitro., Conclusion: PGP increases the Ca2+ content in intestinal mucosa partly through controlling the regulators of Ca2+ mobilization, subsequently promotes intestinal epithelial cell migration, and then prevents intestinal mucosal injury induced by indomethacin., Competing Interests: All authors have no conflicts of interest to declare., (© 2022 The Korean Society of Ginseng. Publishing services by Elsevier B.V.) more...- Published
- 2023
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4. Suppression of P-glycoprotein gene expression in Hs578T/Dox by the overexpression of caveolin-1
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Zhu, Hua, Cai, Chuanxi, and Chen, Jianwen
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GENE expression , *GENETIC regulation , *MOLECULAR cloning , *DNA polymerases - Abstract
Caveolin-1, the principal component of caveolae, is a 21–24 kDa integral membrane protein. The interaction of the caveolin-1 scaffolding domain with signaling molecules can functionally inhibit the activity of these signaling proteins. Little is known about how caveolin-1 influences the expression of P-glycoprotein (P-gp), an ABC transporter encoded by multi-drug resistance (MDR1) gene. To elucidate the possible mechanism between caveolin-1 and P-gp expression, in the present study, we overexpressed caveolin-1 in the Hs578T/Dox breast adenocarcinoma cells, a multidrug resistant line, and then selected single clone cells highly expressing caveolin-1 level. Both Western blot and confocal microscopy analyses showed that caveolin-1 was markedly overexpressed in the transfectants, while P-gp protein was almost abolished. Reverse transcription polymerase chain reaction also showed that the expression of P-gp mRNA was significantly suppressed in the transfectants. It was confirmed further by Northern blot analysis. Moreover, through measuring the changes of drug resistance and P-gp transport activity in the transfectants, we found that overexpression of caveolin-1 reversed drug resistance of transfectants and lowered their P-gp transport activity to the level of Hs578T/S. Taken together, our results indicate that such suppression of P-gp in the transfectants overexpressing caveolin-1 may occur at the transcriptional level. [Copyright &y& Elsevier] more...
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- 2004
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5. Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia/reperfusion-induced cerebral microcirculatory disturbances and neuron damage
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Kai Sun, Jing-Yan Han, and Jing-Yu Fan
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OGD, oxygen-glucose deprivation ,MPO, myeloperoxidase ,Brain blood barrier ,Review ,ICAM-1, intercellular adhesion molecule-1 ,Traditional Chinese medicine ,JAM-1, junctional adhesion molecule-1 ,BNDF, brain-derived neurotrophic factor ,ZO-1, zonula occludens-1 ,Cognitive disabilities ,bFGF, basic fibroblast growth factor ,ERK, extracellular signal-regulated kinase ,GSH, glutathione ,RANTES, regulated upon activation normal T-cell expressed and secreted ,Asian country ,BMEC, brain microvascular endothelial cell ,General Pharmacology, Toxicology and Pharmaceutics ,IL-8, interleukin-8 ,ICAM-1 ,I-κBα, Inhibitory κBα ,LDH, lactate dehydrogenase ,GRK2, G protein-coupled receptor kinase 2 ,GSSH, glutathione disulfide ,HE, hematoxylin and eosin ,Cav-1, caveolin-1 ,IL-10, interleukin-10 ,TTC, 2,3,5-triphenyltetrazolium chloride ,Hyperpermeability ,I/R, ischemia-reperfusion ,VEGF, vascular endothelial growth factor ,cAMP, cyclic adenosine monophosphate ,HIF, hypoxia-inducible factor ,medicine.anatomical_structure ,HPLC, high performance liquid chromatography ,COX-2, cyclooxygenase-2 ,JNK, Jun N-terminal kinase ,iNOS, inducible nitric oxide synthase ,TBARS, thiobarbituric acid reactive substance ,Cardiology ,Antioxidant ,CBF, cerebral blood flow ,TCM, traditional Chinese medicine ,Gly, glysine ,AIF, apoptosis inducing factor ,Perfusion ,AP-1, activator protein-1 ,PARP, poly-ADP-ribose polymerase ,Asp, aspartate ,medicine.medical_specialty ,AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ,GSH-Px, glutathione peroxidase ,IL-1β, interleukin-1β ,NGF, nerve growth factor ,rtPA, recombinant tissue plasminogen activator ,Ischemia ,Materia medica ,Ischemia/reperfusion ,PMN, polymorphonuclear ,BBB, brain blood barrier ,8-OHdG, 8-hydroxydeoxyguanosine ,ROS, reactive oxygen species ,SOD, superoxide dismutase ,Internal medicine ,VCAM-1, vascular adhesion molecule-1 ,medicine ,NMDA, N-methyl-d-aspartic acid ,NSC, neural stem cells ,MCAO, middle cerebral artery occlusion ,TNF-α, tissue necrosis factor-α ,MDA, malondialdehyde ,NO, nitric oxide ,Glu, glutamate ,business.industry ,lcsh:RM1-950 ,TGF-β1, transforming growth factor β1 ,Neuron ,NADPH, nicotinamide adenine dinucleotide phosphate ,NF-κB, nuclear factor κ-B ,medicine.disease ,Tuj-1, class III β-tublin ,hs-CRP, high-sensitivity C-reactive protein ,lcsh:Therapeutics. Pharmacology ,TIMP-1, tissue inhibitor of metalloproteinase-1 ,Leukocyte adhesion ,TUNEL, terminal-deoxynucleoitidyl transferase mediated nick end labeling ,Immunology ,MMPs, matrix metalloproteinases ,DPPH, 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl ,CAT, catalase ,business ,DHR, dihydrorhodamine 123 ,GABA, γ-aminobutyric acid ,MRI, magnetic resonance imaging ,MAPK, mitogen activated protein kinase ,SFDA, state food and drug administration - Abstract
Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM) has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound TCM preparation, Chinese materia medica, and active components on I/R-induced cerebral microcirculatory disturbances, brain injury and neuron damage., Graphical abstract TCM preparation, Chinese materia medica and their active compounds show potential to ameliorate I/R-induced cerebral microcirculatory disturbances, brain injury and neuron damage with anti-inflammation, anti-oxidation, anti-apoptosis, anti-excitoxicity and pro-neurogenesis as the major underlying mechanisms. more...
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- 2015
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6. Exploration and insights into the cellular internalization and intracellular fate of amphiphilic polymeric nanocarriers.
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Mazumdar S, Chitkara D, and Mittal A
- Abstract
The beneficial or deleterious effects of nanomedicines emerge from their complex interactions with intracellular pathways and their subcellular fate. Moreover, the dynamic nature of plasma membrane accounts for the movement of these nanocarriers within the cell towards different organelles thereby not only influencing their pharmacokinetic and pharmacodynamic properties but also bioavailability, therapeutic efficacy and toxicity. Therefore, an in-depth understanding of underlying parameters controlling nanocarrier endocytosis and intracellular fate is essential. In order to direct nanoparticles towards specific sub-cellular organelles the physicochemical attributes of nanocarriers can be manipulated. These include particle size, shape and surface charge/chemistry. Restricting the particle size of nanocarriers below 200 nm contributes to internalization via clathrin and caveolae mediated pathways. Similarly, a moderate negative surface potential confers endolysosomal escape and targeting towards mitochondria, endoplasmic reticulum (ER) and Golgi. This review aims to provide an insight into these physicochemical attributes of nanocarriers fabricated using amphiphilic graft copolymers affecting cellular internalization. Fundamental principles understood from experimental studies have been extrapolated to draw a general conclusion for the designing of optimized nanoparticulate drug delivery systems and enhanced intracellular uptake via specific endocytic pathway., Competing Interests: The authors (Deepak Chitkara and Anupama Mittal) are the founding directors of Nanobrid Innovations Private Limited that is involved in the development of nanotechnology based products. They have business and/or financial interest in the operations of the company. The same could be disclosed on request. The authors declare that they have no conflict of interest pertaining to the work outlined in this study., (© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.) more...
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- 2021
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7. Molecular mechanism of statin-mediated LOX-1 inhibition
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Silvia Biocca, Mattia Falconi, Federico Iacovelli, Francesco Oteri, Sara Matarazzo, Giulia Vindigni, Alessandro Desideri, Biologie Computationnelle et Quantitative = Laboratory of Computational and Quantitative Biology (LCQB), Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma Tor Vergata [Roma], FILAS, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) more...
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CTLD ,[SDV]Life Sciences [q-bio] ,ox-LDL ,01 natural sciences ,Pathogenesis ,chemistry.chemical_compound ,Chlorocebus aethiops ,1′-dioctadecyl-3 ,3-hydroxy-3-methylglutaryl coenzyme A ,Receptor ,0303 health sciences ,Mab ,pravastatin ,010304 chemical physics ,medicine.diagnostic_test ,Settore BIO/11 ,Protein Stability ,Dulbecco's modified Eagle's medium ,atorvastatin ,Ligand (biochemistry) ,monomer-dimer ratio ,Scavenger Receptors, Class E ,3′ ,3 ` ,Lov ,3. Good health ,Lipoproteins, LDL ,Molecular Docking Simulation ,lectin-like oxidized low-density lipoprotein receptor-1 ,molecular dynamics simulation ,Biochemistry ,COS Cells ,lipids (amino acids, peptides, and proteins) ,Lovastatin ,Dimerization ,medicine.drug ,DiI ,Cav-1 ,Protein Binding ,caveolin-1 ,Statin ,3′-tetramethyllindocarbocyanine perchlorate ,Flu ,medicine.drug_class ,fluvastatin ,human embryonic kidney ,DMEM ,3 `-tetramethyllindocarbocyanine perchlorate ,Biology ,LDL ,03 medical and health sciences ,Western blot ,HMG-CoA ,Report ,0103 physical sciences ,medicine ,Animals ,Humans ,LDL-C ,Molecular Biology ,030304 developmental biology ,Fluorescent Dyes ,HEK ,oxidized low-density lipoprotein ,Binding Sites ,Cholesterol ,Ato, atorvastatin ,CTLD, C-type lectin-like domain ,Cav-1, caveolin-1 ,DMEM, Dulbecco's modified Eagle's medium ,DiI, 1,1′-dioctadecyl-3,3,3′,3′-tetramethyllindocarbocyanine perchlorate ,Flu, fluvastatin ,HEK, human embryonic kidney ,HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A ,LDL, low-density lipoprotein ,LDL-C, low-density lipoprotein-cholesterol ,LOX-1 receptor ,LOX-1, lectin-like oxidized low-density lipoprotein receptor-1 ,Lov, lovastatin ,Mab, monoclonal antibody ,Pra, pravastatin ,molecular docking ,ox-LDL, oxidized low-density lipoprotein ,statin ,substrate recognition ,Ligand binding assay ,1 `-dioctadecyl-3 ,Cell Biology ,low-density lipoprotein-cholesterol ,Protein Structure, Tertiary ,Pra ,LOX-1 ,HEK293 Cells ,chemistry ,low-density lipoprotein ,Microscopy, Fluorescence ,monoclonal antibody ,C-type lectin-like domain ,Biophysics ,Ato ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Developmental Biology - Abstract
International audience; Statins are largely used in clinics in the treatment of patients with cardiovascular diseases for their effect on lowering circulating cholesterol. Lectin-like oxidized low-density lipoprotein (LOX-1), the primary receptor for ox-LDL, plays a central role in the pathogenesis of atherosclerosis and cardiovascular disorders. We have recently shown that chronic exposure of cells to lovastatin disrupts LOX-1 receptor cluster distribution in plasma membranes, leading to a marked loss of LOX-1 function. Here we investigated the molecular mechanism of statin-mediated LOX-1 inhibition and we demonstrate that all tested statins are able to displace the binding of fluorescent ox-LDL to LOX-1 by a direct interaction with LOX-1 receptors in a cell-based binding assay. Molecular docking simulations confirm the interaction and indicate that statins completely fill the hydrophobic tunnel that crosses the C-type lectin-like (CTLD) recognition domain of LOX-1. Classical molecular dynamics simulation technique applied to the LOX-1 CTLD, considered in the entire receptor structure with or without a statin ligand inside the tunnel, indicates that the presence of a ligand largely increases the dimer stability. Electrophoretic separation and western blot confirm that different statins binding stabilize the dimer assembly of LOX-1 receptors in vivo. The simulative and experimental results allow us to propose a CTLD clamp motion, which enables the receptor-substrate coupling. These findings reveal a novel and significant functional effect of statins. more...
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- 2015
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8. Vascular smooth muscle cell proliferation depends on caveolin-1-regulated polyamine uptake
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Karl Swärd, Amalia Forte, Per Hellstrand, Mario Grossi, Ramasri Sathanoori, Lo Persson, Bengt-Olof Nilsson, David Erlinge, and Catarina Rippe
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HBSS, Hanks balanced salt solution ,Vascular smooth muscle ,[3H]Put, [3H]putrescine ,Cell ,Caveolin 1 ,lcsh:Life ,lcsh:QR1-502 ,Gene Expression ,Muscle Proteins ,Biochemistry ,lcsh:Microbiology ,DMEM, Dulbecco’s modified Eagle’s medium ,VSMC, vascular smooth muscle cell ,Muscle, Smooth, Vascular ,Ornithine decarboxylase ,HRP, horseradish peroxidise ,chemistry.chemical_compound ,polyamine ,Cell Movement ,Polyamines ,Myocyte ,ornithine decarboxylase ,Cardiac and Cardiovascular Systems ,Cells, Cultured ,Mice, Knockout ,Reverse Transcriptase Polymerase Chain Reaction ,Microfilament Proteins ,Cav-1, caveolin-1 ,qRT-PCR, quantitative real-time PCR ,Cell cycle ,Immunohistochemistry ,[3H]Spd, [3H]spermidine ,medicine.anatomical_structure ,Carotid Arteries ,cardiovascular system ,cell cycle ,DFMO, difluoromethylornithine ,caveolin-1 ,Calponin ,Blotting, Western ,Myocytes, Smooth Muscle ,Biophysics ,Biology ,Ornithine Decarboxylase ,S2 ,PI, propidium iodide ,medicine ,Animals ,HSP90, heat-shock protein 90 ,Rats, Wistar ,Molecular Biology ,Cell Proliferation ,Original Paper ,KO, knockout ,Cell growth ,Calcium-Binding Proteins ,Cell Biology ,DNA ,polyamine transporter ,Molecular biology ,WT, wild-type ,Mice, Inbred C57BL ,lcsh:QH501-531 ,ASMC, aortic smooth muscle cell ,chemistry ,CEA, carotid endarterectomy ,ODC, ornithine decarboxylase ,biology.protein ,Amino Acid Transport Systems, Basic ,vascular smooth muscle cell ,Polyamine ,Cell and Molecular Biology - Abstract
Much evidence highlights the importance of polyamines for VSMC (vascular smooth muscle cell) proliferation and migration. Cav-1 (caveolin-1) was recently reported to regulate polyamine uptake in intestinal epithelial cells. The aim of the present study was to assess the importance of Cav-1 for VSMC polyamine uptake and its impact on cell proliferation and migration. Cav-1 KO (knockout) mouse aortic cells showed increased polyamine uptake and elevated proliferation and migration compared with WT (wild-type) cells. Both Cav-1 KO and WT cells expressed the smooth muscle differentiation markers SM22 and calponin. Cell-cycle phase distribution analysis revealed a higher proportion of Cav-1 KO than WT cells in the S phase. Cav-1 KO cells were hyper-proliferative in the presence but not in the absence of extracellular polyamines, and, moreover, supplementation with exogenous polyamines promoted proliferation in Cav-1 KO but not in WT cells. Expression of the solute carrier transporters Slc7a1 and Slc43a1 was higher in Cav-1 KO than in WT cells. ODC (ornithine decarboxylase) protein and mRNA expression as well as ODC activity were similar in Cav-1 KO and WT cells showing unaltered synthesis of polyamines in Cav-1 KO cells. Cav-1 was reduced in migrating cells in vitro and in carotid lesions in vivo. Our data show that Cav-1 negatively regulates VSMC polyamine uptake and that the proliferative advantage of Cav-1 KO cells is critically dependent on polyamine uptake. We provide proof-of-principle for targeting Cav-1-regulated polyamine uptake as a strategy to fight unwanted VSMC proliferation as observed in restenosis., We demonstrate that caveolin-1 negatively regulates vascular smooth muscle cell polyamine uptake and show that caveolin-1-regulated polyamine uptake is critical for proliferative advantage of caveolin-1 deficient cells, providing proof-of-principle for targeting this mechanism as a strategy to fight unwanted proliferation. more...
- Published
- 2014
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