Nanomolar Caffeic Acid Decreases Glucose Uptake and the Effects of High Glucose in Endothelial Cells
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{"title"=>"Nanomolar caffeic acid decreases glucose uptake and the effects of high glucose in endothelial cells", "type"=>"journal", "authors"=>[{"first_name"=>"Lucia", "last_name"=>"Natarelli", "scopus_author_id"=>"56011402500"}, {"first_name"=>"Giulia", "last_name"=>"Ranaldi", "scopus_author_id"=>"6505785643"}, {"first_name"=>"Guido", "last_name"=>"Leoni", "scopus_author_id"=>"34977070800"}, {"first_name"=>"Marianna", "last_name"=>"Roselli", "scopus_author_id"=>"8121879900"}, {"first_name"=>"Barbara", "last_name"=>"Guantario", "scopus_author_id"=>"24366764000"}, {"first_name"=>"Raffaella", "last_name"=>"Comitato", "scopus_author_id"=>"7801604405"}, {"first_name"=>"Roberto", "last_name"=>"Ambra", "scopus_author_id"=>"6603647201"}, {"first_name"=>"Francesco", "last_name"=>"Cimino", "scopus_author_id"=>"7005865156"}, {"first_name"=>"Antonio", "last_name"=>"Speciale", "scopus_author_id"=>"55950056900"}, {"first_name"=>"Fabio", "last_name"=>"Virgili", "scopus_author_id"=>"7004157939"}, {"first_name"=>"Raffaella", "last_name"=>"Canali", "scopus_author_id"=>"6602487732"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"607426671", "sgr"=>"84952684646", "issn"=>"19326203", "pmid"=>"26544184", "scopus"=>"2-s2.0-84952684646", "doi"=>"10.1371/journal.pone.0142421"}, "id"=>"0ca2c69a-141c-32c4-b425-f7e726cf3541", "abstract"=>"Epidemiological studies suggest that moderate and prolonged consumption of coffee is associated with a reduced risk of developing type 2 diabetes but the molecular mechanisms underlying this effect are not known. In this study, we report the effects of physiological concentrations of caffeic acid, easily achievable by normal dietary habits, in endothelial cells cultured in 25 mM of glucose (high glucose, HG). In HG, the presence of 10 nM caffeic acid was associated with a decrease of glucose uptake but not to changes of GLUT-1 membrane localization or mRNA levels. Moreover, caffeic acid countered HG-induced loss of barrier integrity, reducing actin rearrangement and FITC-dextran passage. The decreased flux of glucose associated to caffeic acid affected HG induced apoptosis by down-regulating the expression of initiator (caspase 8 and 9) and effector caspases (caspase 7 and 3) and by increasing the levels of phosphorylated Bcl-2. We also observed that caffeic acid in HG condition was associated to a reduction of p65 subunit nuclear levels with respect to HG alone. NF-κB activation has been shown to lead to apoptosis in HG treated cells and the analysis of the expression of a panel of about 90 genes related to NF-κB signaling pathway revealed that caffeic acid significantly influenced gene expression changes induced by HG. In conclusion, our results suggest that caffeic acid, decreasing the metabolic stress induced by HG, allows the activation of survival mechanisms mediated by a different modulation of NF-κB-related signaling pathways and to the activation of anti-apoptotic proteins.", "link"=>"http://www.mendeley.com/research/nanomolar-caffeic-acid-decreases-glucose-uptake-effects-high-glucose-endothelial-cells", "reader_count"=>5, "reader_count_by_academic_status"=>{"Student > Doctoral Student"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>2, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Student > Doctoral Student"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>2, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>1, "Medicine and Dentistry"=>1, "Sports and Recreations"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Germany"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2416344"], "description"=>"<p>Cells were seeded onto PET Transwell filters and incubated in control, HG or CA+HG conditions for 48 hours. Cells were fixed in 2% PFA and permeabilized with 0.1% Triton X-100. F-actin filaments and nuclei were stained with FITC-conjugated phalloidin (green) and DAPI (blue), respectively. White arrows indicate peripheral F-actin. The image reports one out of at least 3 independent experiments.</p>", "links"=>[], "tags"=>["glut", "Decreases Glucose Uptake", "caffeic acid", "hg", "caspase", "type 2 diabetes", "nf", "glucose", "p 65 subunit", "10 nM caffeic acid", "gene expression changes", "activation"], "article_id"=>1596739, "categories"=>["Uncategorised"], "users"=>["Lucia Natarelli", "Giulia Ranaldi", "Guido Leoni", "Marianna Roselli", "Barbara Guantario", "Raffaella Comitato", "Roberto Ambra", "Francesco Cimino", "Antonio Speciale", "Fabio Virgili", "Raffaella Canali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142421.g003", "stats"=>{"downloads"=>5, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CA_reduces_HG_dependent_actin_reassessment_/1596739", "title"=>"CA reduces HG-dependent actin reassessment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-06 04:00:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2416350"], "description"=>"<p>Cells were treated for 24, 48 and 72 hours as indicated in the figures. Panels show: A) cell count expressed as number of cells per well; B) Proliferation analysis by BrdU incorporation; C) Representative dot plots of cell distribution after double labeling with Annexin-V and PI. Data are expressed as percentage of induction of early (Annexin V positive cells) and late stages of apoptosis (Annexin-V/PI double positive cells). *p<0.05 HG <i>vs</i> control; **p<0.001 <i>vs</i> control; # p<0.05 CA+HG <i>vs</i> HG. ## p< 0.001 and ### p< 0.0001 CA+HG <i>vs</i> HG. Values are the mean ± SEM from at least 3 independent experiments.</p>", "links"=>[], "tags"=>["glut", "Decreases Glucose Uptake", "caffeic acid", "hg", "caspase", "type 2 diabetes", "nf", "glucose", "p 65 subunit", "10 nM caffeic acid", "gene expression changes", "activation"], "article_id"=>1596742, "categories"=>["Uncategorised"], "users"=>["Lucia Natarelli", "Giulia Ranaldi", "Guido Leoni", "Marianna Roselli", "Barbara Guantario", "Raffaella Comitato", "Roberto Ambra", "Francesco Cimino", "Antonio Speciale", "Fabio Virgili", "Raffaella Canali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142421.g004", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_CA_on_cell_proliferation_and_apoptosis_/1596742", "title"=>"Effect of CA on cell proliferation and apoptosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-06 04:00:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2416353"], "description"=>"<p>A) A representative Western blot of procaspase and cleaved caspase-8 after 12 hours of treatments. B) A representative Western blot of caspase-7 and procaspase-9 after 12 and 24 hours of treatments. C) A representative Western blot of procaspase and cleaved caspase-3 after 12 hours of treatments. Caspase 3 activity was measured by detection of fluorescence of the caspase substrate after 12, 24 and 36 hours of treatments. Data are expressed as relative AFC (7-amino-4-trifluoromethylcpumarin) fluorescence normalized for total protein content in each sample. D) Effect of CA on phosphorylated Bcl-2 protein levels at 12 and 24 hours of treatments. Images report one representative experiment out of at least 3 independent experiments.*p<0.05 <i>vs</i> control; **p<0.001 <i>vs</i> control; # p<0.05 CA+HG <i>vs</i> HG.</p>", "links"=>[], "tags"=>["glut", "Decreases Glucose Uptake", "caffeic acid", "hg", "caspase", "type 2 diabetes", "nf", "glucose", "p 65 subunit", "10 nM caffeic acid", "gene expression changes", "activation"], "article_id"=>1596744, "categories"=>["Uncategorised"], "users"=>["Lucia Natarelli", "Giulia Ranaldi", "Guido Leoni", "Marianna Roselli", "Barbara Guantario", "Raffaella Comitato", "Roberto Ambra", "Francesco Cimino", "Antonio Speciale", "Fabio Virgili", "Raffaella Canali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142421.g005", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_activated_caspases_and_anti_apoptotic_Bcl_2_/1596744", "title"=>"Analysis of activated caspases and anti-apoptotic Bcl-2.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-06 04:00:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2416356"], "description"=>"<p>Cells were incubated with CA, HG or CA+HG for 3, 6 and 12 hours *p<0.05 <i>vs</i> control; **p<0.001 <i>vs</i> control; #p<0.05 CA+HG <i>vs</i> HG. The image reports one out of at least 3 independent experiments.</p>", "links"=>[], "tags"=>["glut", "Decreases Glucose Uptake", "caffeic acid", "hg", "caspase", "type 2 diabetes", "nf", "glucose", "p 65 subunit", "10 nM caffeic acid", "gene expression changes", "activation"], "article_id"=>1596746, "categories"=>["Uncategorised"], "users"=>["Lucia Natarelli", "Giulia Ranaldi", "Guido Leoni", "Marianna Roselli", "Barbara Guantario", "Raffaella Comitato", "Roberto Ambra", "Francesco Cimino", "Antonio Speciale", "Fabio Virgili", "Raffaella Canali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142421.g006", "stats"=>{"downloads"=>5, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_p65_nuclear_localization_/1596746", "title"=>"p65 nuclear localization.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-06 04:00:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2416358"], "description"=>"<p>The heatmap reflects the differently regulated gene expression values in CA+HG and HG (12 hours of incubation) respect to control. Color scheme goes from red for upregulated genes to blue for down-regulated genes. Data are expressed as the median of log2 of Fold Change (FC).</p>", "links"=>[], "tags"=>["glut", "Decreases Glucose Uptake", "caffeic acid", "hg", "caspase", "type 2 diabetes", "nf", "glucose", "p 65 subunit", "10 nM caffeic acid", "gene expression changes", "activation"], "article_id"=>1596747, "categories"=>["Uncategorised"], "users"=>["Lucia Natarelli", "Giulia Ranaldi", "Guido Leoni", "Marianna Roselli", "Barbara Guantario", "Raffaella Comitato", "Roberto Ambra", "Francesco Cimino", "Antonio Speciale", "Fabio Virgili", "Raffaella Canali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142421.g007", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Heat_map_generated_from_StellARray_8482_qPCR_data_/1596747", "title"=>"Heat map generated from StellARray<sup>™</sup> qPCR data.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-06 04:00:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2416361"], "description"=>"<p>The color of the nodes represents the FC expression associates to HG, the color of the frame of the nodes corresponds to the FC expression associated to AC+HG. The color intensity of the nodes is associated to the FC rate as indicated in the figure.</p>", "links"=>[], "tags"=>["glut", "Decreases Glucose Uptake", "caffeic acid", "hg", "caspase", "type 2 diabetes", "nf", "glucose", "p 65 subunit", "10 nM caffeic acid", "gene expression changes", "activation"], "article_id"=>1596749, "categories"=>["Uncategorised"], "users"=>["Lucia Natarelli", "Giulia Ranaldi", "Guido Leoni", "Marianna Roselli", "Barbara Guantario", "Raffaella Comitato", "Roberto Ambra", "Francesco Cimino", "Antonio Speciale", "Fabio Virgili", "Raffaella Canali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142421.g008", "stats"=>{"downloads"=>5, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mapping_of_the_significant_modulated_genes_within_Reactome_pathways_database_tool_/1596749", "title"=>"Mapping of the significant modulated genes within Reactome pathways database tool.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-06 04:00:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2416362", "https://ndownloader.figshare.com/files/2416363", "https://ndownloader.figshare.com/files/2416364"], "description"=>"<div><p>Epidemiological studies suggest that moderate and prolonged consumption of coffee is associated with a reduced risk of developing type 2 diabetes but the molecular mechanisms underlying this effect are not known. In this study, we report the effects of physiological concentrations of caffeic acid, easily achievable by normal dietary habits, in endothelial cells cultured in 25 mM of glucose (high glucose, HG). In HG, the presence of 10 nM caffeic acid was associated with a decrease of glucose uptake but not to changes of GLUT-1 membrane localization or mRNA levels. Moreover, caffeic acid countered HG-induced loss of barrier integrity, reducing actin rearrangement and FITC-dextran passage. The decreased flux of glucose associated to caffeic acid affected HG induced apoptosis by down-regulating the expression of initiator (caspase 8 and 9) and effector caspases (caspase 7 and 3) and by increasing the levels of phosphorylated Bcl-2. We also observed that caffeic acid in HG condition was associated to a reduction of p65 subunit nuclear levels with respect to HG alone. NF-κB activation has been shown to lead to apoptosis in HG treated cells and the analysis of the expression of a panel of about 90 genes related to NF-κB signaling pathway revealed that caffeic acid significantly influenced gene expression changes induced by HG. In conclusion, our results suggest that caffeic acid, decreasing the metabolic stress induced by HG, allows the activation of survival mechanisms mediated by a different modulation of NF-κB-related signaling pathways and to the activation of anti-apoptotic proteins.</p></div>", "links"=>[], "tags"=>["glut", "Decreases Glucose Uptake", "caffeic acid", "hg", "caspase", "type 2 diabetes", "nf", "glucose", "p 65 subunit", "10 nM caffeic acid", "gene expression changes", "activation"], "article_id"=>1596750, "categories"=>["Uncategorised"], "users"=>["Lucia Natarelli", "Giulia Ranaldi", "Guido Leoni", "Marianna Roselli", "Barbara Guantario", "Raffaella Comitato", "Roberto Ambra", "Francesco Cimino", "Antonio Speciale", "Fabio Virgili", "Raffaella Canali"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0142421.s001", "https://dx.doi.org/10.1371/journal.pone.0142421.s002", "https://dx.doi.org/10.1371/journal.pone.0142421.s003"], "stats"=>{"downloads"=>10, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nanomolar_Caffeic_Acid_Decreases_Glucose_Uptake_and_the_Effects_of_High_Glucose_in_Endothelial_Cells_/1596750", "title"=>"Nanomolar Caffeic Acid Decreases Glucose Uptake and the Effects of High Glucose in Endothelial Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-11-06 04:00:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2416334"], "description"=>"<p>Sub-confluent cells were incubated in control, CA, HG or CA+HG conditions for 30 min, 3, 6, 24 and 48 hours. At the end of the incubation, cells were treated with 100 μM 2-dGlu and 0.1 μCi/ml 2-deoxy-D- [C14]glucose for 5 minutes. At the end of the incubation, radioactivity in cell lysate was detected by scintillation counting. The rate of glucose was expressed in pmol dGlu/min/μg protein and shown in the figure as % of control at each time point. Values are the mean ± SD from at least 3 independent experiments. *p<0.05 HG <i>vs</i> control; ***p<0.0001 <i>vs</i> control; #p<0.05 AC+HG <i>vs</i> HG; α p<0.001 versus CA.</p>", "links"=>[], "tags"=>["glut", "Decreases Glucose Uptake", "caffeic acid", "hg", "caspase", "type 2 diabetes", "nf", "glucose", "p 65 subunit", "10 nM caffeic acid", "gene expression changes", "activation"], "article_id"=>1596733, "categories"=>["Uncategorised"], "users"=>["Lucia Natarelli", "Giulia Ranaldi", "Guido Leoni", "Marianna Roselli", "Barbara Guantario", "Raffaella Comitato", "Roberto Ambra", "Francesco Cimino", "Antonio Speciale", "Fabio Virgili", "Raffaella Canali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142421.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_CA_on_glucose_uptake_/1596733", "title"=>"Effect of CA on glucose uptake.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-06 04:00:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/2416336"], "description"=>"<p>Cells were seeded onto PET Transwell filters and incubated in control, CA, HG and CA+ HG conditions for 24, 30, 48 and 72 hours. FITC-FD40 was added to a final concentration of 500 μg/ml in the apical medium. The fluorescence was measured both in basal and apical medium. Data are presented as percentage of the ratios of FD40 basal <i>vs</i> apical fluorescence. ***p<0.0001 <i>vs</i> control; n.d. = not detected. Values are the mean ± SEM from at least 3 independent experiments.</p>", "links"=>[], "tags"=>["glut", "Decreases Glucose Uptake", "caffeic acid", "hg", "caspase", "type 2 diabetes", "nf", "glucose", "p 65 subunit", "10 nM caffeic acid", "gene expression changes", "activation"], "article_id"=>1596735, "categories"=>["Uncategorised"], "users"=>["Lucia Natarelli", "Giulia Ranaldi", "Guido Leoni", "Marianna Roselli", "Barbara Guantario", "Raffaella Comitato", "Roberto Ambra", "Francesco Cimino", "Antonio Speciale", "Fabio Virgili", "Raffaella Canali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142421.g002", "stats"=>{"downloads"=>3, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CA_protects_HG_dependent_loss_of_endothelial_barrier_integrity_/1596735", "title"=>"CA protects HG-dependent loss of endothelial barrier integrity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-06 04:00:46"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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