Adenosine Prevents TNFα-Induced Decrease in Endothelial Mitochondrial Mass via Activation of eNOS-PGC-1α Regulatory Axis
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{"title"=>"Adenosine prevents TNFα-induced decrease in endothelial mitochondrial mass via activation of eNOS-PGC-1α regulatory axis", "type"=>"journal", "authors"=>[{"first_name"=>"Theodore J.", "last_name"=>"Kalogeris", "scopus_author_id"=>"7003731470"}, {"first_name"=>"Christopher", "last_name"=>"Baines", "scopus_author_id"=>"35267768400"}, {"first_name"=>"Ronald J.", "last_name"=>"Korthuis", "scopus_author_id"=>"7006497764"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"373337802", "sgr"=>"84902603260", "issn"=>"19326203", "pmid"=>"24914683", "scopus"=>"2-s2.0-84902603260", "doi"=>"10.1371/journal.pone.0098459", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"24e4a69c-ea06-3388-ab20-8d587e2c7d84", "abstract"=>"We tested whether adenosine, a cytoprotective mediator and trigger of preconditioning, could protect endothelial cells from inflammation-induced deficits in mitochondrial biogenesis and function. We examined this question using human microvascular endothelial cells exposed to TNFalpha. TNFalpha produced time and dose-dependent decreases in mitochondrial membrane potential, cellular ATP levels, and mitochondrial mass, preceding an increase in apoptosis. These effects were prevented by co-incubation with adenosine, a nitric oxide (NO) donor, a guanylate cyclase (GC) activator, or a cell-permeant cyclic GMP (cGMP) analog. The effects of adenosine were blocked by a nitric oxide synthase inhibitor, a soluble guanylate cyclase inhibitor, a morpholino antisense oligonucleotide to endothelial nitric oxide synthase (eNOS), or siRNA knockdown of the transcriptional coactivator, PGC-1alpha. Incubation with exogenous NO, a GC activator, or a cGMP analog reversed the effect of eNOS knockdown, while the effect of NO was blocked by inhibition of GC. The protective effects of NO and cGMP analog were prevented by siRNA to PGC-1alpha. TNFalpha also decreased expression of eNOS, cellular NO levels, and PGC-1alpha expression, which were reversed by adenosine. Exogenous NO, but not adenosine, rescued expression of PGC-1alpha in cells in which eNOS expression was knocked down by eNOS antisense treatment. Thus, TNFalpha elicits decreases in endothelial mitochondrial function and mass, and an increase in apoptosis. These effects were reversed by adenosine, an effect mediated by eNOS-synthesized NO, acting via soluble guanylate cyclase/cGMP to activate a mitochondrial biogenesis regulatory program under the control of PGC-1alpha. These results support the existence of an adenosine-triggered, mito-and cytoprotective mechanism dependent upon an eNOS-PGC-1alpha regulatory pathway, which acts to preserve endothelial mitochondrial function and mass during inflammatory challenge.", "link"=>"http://www.mendeley.com/research/adenosine-prevents-tnf%CE%B1induced-decrease-endothelial-mitochondrial-mass-via-activation-enospgc1%CE%B1-regu", "reader_count"=>7, "reader_count_by_academic_status"=>{"Researcher"=>1, "Student > Doctoral Student"=>1, "Student > Postgraduate"=>1, "Student > Bachelor"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Researcher"=>1, "Student > Doctoral Student"=>1, "Student > Postgraduate"=>1, "Student > Bachelor"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>2, "Medicine and Dentistry"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>4}}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1528449"], "description"=>"<p>Effect of TNFα dose and time of incubation on cellular ATP levels.</p>", "links"=>[], "tags"=>["anatomy", "biological tissue", "epithelium", "Epithelial cells", "Endothelial cells", "Biochemistry", "Bioenergetics", "Energy-producing organelles", "Neurochemistry", "Neurochemicals", "Nitric oxide", "cell biology", "Cell processes", "Cell death", "Cellular types", "Molecular cell biology", "genetics", "epigenetics", "RNA interference", "gene expression", "neuroscience", "cardiology", "incubation", "cellular", "atp"], "article_id"=>1052000, "categories"=>["Biological Sciences"], "users"=>["Theodore J. Kalogeris", "Christopher Baines", "Ronald J. Korthuis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0098459.t001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_TNF_945_dose_and_time_of_incubation_on_cellular_ATP_levels_/1052000", "title"=>"Effect of TNFα dose and time of incubation on cellular ATP levels.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-06-10 02:49:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1528451"], "description"=>"<p>Cellular ATP levels after incubation with TNFα in the presence or absence of adenosine.</p>", "links"=>[], "tags"=>["anatomy", "biological tissue", "epithelium", "Epithelial cells", "Endothelial cells", "Biochemistry", "Bioenergetics", "Energy-producing organelles", "Neurochemistry", "Neurochemicals", "Nitric oxide", "cell biology", "Cell processes", "Cell death", "Cellular types", "Molecular cell biology", "genetics", "epigenetics", "RNA interference", "gene expression", "neuroscience", "cardiology", "atp", "incubation"], "article_id"=>1052002, "categories"=>["Biological Sciences"], "users"=>["Theodore J. Kalogeris", "Christopher Baines", "Ronald J. Korthuis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0098459.t002", "stats"=>{"downloads"=>3, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cellular_ATP_levels_after_incubation_with_TNF_945_in_the_presence_or_absence_of_adenosine_/1052002", "title"=>"Cellular ATP levels after incubation with TNFα in the presence or absence of adenosine.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-06-10 02:49:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1528439"], "description"=>"<p>(<b>A</b>) HMEC-1 cells on gelatin-coated glass cover slips were incubated with TNFα at 1 or 10 ng/ml for the indicated period. At each time point, apoptotic cells were fixed, mounted, and stained with DAPI, then counted as described in Methods; apoptosis calculated as a percentage of total cells in 6 fields of view, with 200 cells counted per 40X field. Data analyzed by two-way ANOVA with multiple comparisons using a general linear model. Experiments were repeated 3–4 times per treatment group. At a given time of incubation, * indicates significantly different from respective time point control, P<0.01. (<b>B</b>) HMEC-1 cells in 24-well plates were incubated with TNFα for the indicated times, loaded with TMRM or MTG dyes, then harvested for measurement of Ψ or total mitochondrial mass, respectively, as described in Methods. Data are means ± SEM for 8 replicates for each treatment/time combination, repeated 4 separate times. Data were analyzed as described for panel (A). All TNFα values were significantly different from their respective controls at each time point, differing letters denote significant TNFα dose effects, P<0.05. (<b>C, D</b>) Attenuation of TNFα effects on apoptosis and Ψ, respectively, by adenosine. Cells set up as described for panels (A) & (B) were incubated with or without TNFα (1 or 10 ng/ml), with or without co-incubation with adenosine (Ado, 10 uM) for either 48 or 72 h, then apoptosis or Ψ were measured. Results are expressed as the % change from the respective time point controls. Data are means ± SEM for 4 separate repititions of each experiment. At both time points, all TNFα values were significantly different from respective control values (P<0.001), apoptosis values in response to Ado+TNFα were significantly higher than control at 48 h (TNFα, 10 ng/ml) and at 72 h (both doses of TNFα), p<0.05. * denote significant attenuation of TNFα-induced effect at each time point in response to Ado (P<0.001).</p>", "links"=>[], "tags"=>["anatomy", "biological tissue", "epithelium", "Epithelial cells", "Endothelial cells", "Biochemistry", "Bioenergetics", "Energy-producing organelles", "Neurochemistry", "Neurochemicals", "Nitric oxide", "cell biology", "Cell processes", "Cell death", "Cellular types", "Molecular cell biology", "genetics", "epigenetics", "RNA interference", "gene expression", "neuroscience", "cardiology", "dose-dependent", "hmec-1", "apoptosis", "mitochondrial", "membrane", "modulation"], "article_id"=>1051990, "categories"=>["Biological Sciences"], "users"=>["Theodore J. Kalogeris", "Christopher Baines", "Ronald J. Korthuis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0098459.g001", "stats"=>{"downloads"=>2, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Time_and_TNF_945_dose_dependent_changes_in_HMEC_1_apoptosis_and_mitochondrial_membrane_potential_936_and_modulation_of_TNF_945_effects_by_adenosine_/1051990", "title"=>"Time and TNFα dose-dependent changes in HMEC-1 apoptosis and mitochondrial membrane potential (Ψ), and modulation of TNFα effects by adenosine.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-10 02:49:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1528440"], "description"=>"<p>In separate experiments, HMEC-1 cells in 100 cm plates were incubated with TNFα (1 ng/ml), then 4 separate indices of mitochondrial content were examined. (<b>A</b>) Time course of effect of TNFα on mitochondrial mass as measured using a fluorescent plate assay for uptake of MTG dye. At the conclusion of TNFα incubation period, cells were loaded with MTG as described in Methods, then harvested and equal aliquots were separately analyzed for MTG fluorescence and total protein. Mitochondrial mass was expressed as MTG fluorescence, normalized for protein content. Experiments were repeated 3–4 times per time point. * denotes significant decrease in apparent mass compared with respective time point control (P<0.0001). (<b>B</b>) Cells prepared as described for panel (A) were incubated in the presence or absence of TNFα (1 ng/ml) for 48 h. Cells were harvested and total DNA was isolated, purified, and subjected to quantitative PCR as described in Methods, using primer sets for both nuclear and mitochondrial DNA (nDNA and mtDNA, respectively). Values are expressed as the mtDNA/nDNA ratio, for 5 separate replications of the experiment. * denotes significant difference from control, p<0.01). (<b>C</b>) Cells prepared and treated as described for panel (B) were harvested and lysates were analyzed for citrate synthase activity as described in Methods. Values summarize the results of 4 separate experiments, * denotes significant difference from control, p<0.05. (<b>D</b>) Cells prepared and treated as described for panel (B) were harvested and lysates were subjected to SDS-PAGE of equal amounts of lysate protein, followed by western blot anlaysis of the indicated proteins. Left-hand panel shows representative blot from among 3 separate experiments, right-hand panel shows semi-quantitative analysis of band density from the full dataset from all experiments. Except for GAPDH, TNFα elicited significantly decreased expression of all proteins examined, p values for each are shown in the figure.</p>", "links"=>[], "tags"=>["anatomy", "biological tissue", "epithelium", "Epithelial cells", "Endothelial cells", "Biochemistry", "Bioenergetics", "Energy-producing organelles", "Neurochemistry", "Neurochemicals", "Nitric oxide", "cell biology", "Cell processes", "Cell death", "Cellular types", "Molecular cell biology", "genetics", "epigenetics", "RNA interference", "gene expression", "neuroscience", "cardiology", "markers", "mitochondrial", "effector", "proteins"], "article_id"=>1051991, "categories"=>["Biological Sciences"], "users"=>["Theodore J. Kalogeris", "Christopher Baines", "Ronald J. Korthuis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0098459.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_TNF_945_on_markers_of_mitochondrial_mass_and_expression_of_several_effector_proteins_for_mitochondrial_biogenesis_/1051991", "title"=>"Effects of TNFα on markers of mitochondrial mass and expression of several effector proteins for mitochondrial biogenesis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-10 02:49:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1528441"], "description"=>"<p>(<b>A</b>) HMEC-1 cells in 100 cm dishes were incubated for 48 h with TNFα (1 ng/ml) in the presence or absence of Ado (10 µM), loaded with MTG, then harvested and MTG fluorescence and protein concentraiton were measured. MTG fluorescence was normalized to protein content; results are expressed as % of control. Experiment was repeated 4 times per group. Both TNFα and Ado+TNFα groups were significantly different from control (p<0.001), differing letters denote significant, between-group differences, p<0.01. (<b>B</b>) Total DNA isolated from cells prepared and treated as described for panel (A) was subjected to analysis by qPCR to obtain mtDNA/nDNA ratios. Experiment was repeated 5–6 times per group. Denoting of statistical differences are as described for panel (A). (<b>C</b>) Mfn-2, porin, and GAPDH expression in cells prepared and treated as described for panel (A), then lysed and subjected to SDS-PAGE followed by western blot. Figure shows representative blot from 3 separate experiments for each group.</p>", "links"=>[], "tags"=>["anatomy", "biological tissue", "epithelium", "Epithelial cells", "Endothelial cells", "Biochemistry", "Bioenergetics", "Energy-producing organelles", "Neurochemistry", "Neurochemicals", "Nitric oxide", "cell biology", "Cell processes", "Cell death", "Cellular types", "Molecular cell biology", "genetics", "epigenetics", "RNA interference", "gene expression", "neuroscience", "cardiology", "adenosine", "markers", "mitochondrial"], "article_id"=>1051992, "categories"=>["Biological Sciences"], "users"=>["Theodore J. Kalogeris", "Christopher Baines", "Ronald J. Korthuis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0098459.g003", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Modulating_effect_of_adenosine_Ado_on_TNF_945_induced_decrease_in_markers_of_mitochondrial_mass_/1051992", "title"=>"Modulating effect of adenosine (Ado) on TNFα-induced decrease in markers of mitochondrial mass.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-10 02:49:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1528442"], "description"=>"<p>(<b>A</b>) Cells were prepared and treated as described for <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0098459#pone-0098459-g003\" target=\"_blank\">Figure 3</a>, except that in one group, cells were preincubated for 15 min with L-NIO (100 µM) prior to addition of Ado and TNFα. Mitochondrial mass was assayed using MTG fluorescence as described for previous figures. Values reported are from 3 separate replications of the experiment per group, differing letters denote significant between-group differences, P<0.05. (<b>B</b>) Western blot of total eNOS expression in response to TNFα vs. Ado+TNFα; blot shown is from the same experiment shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0098459#pone-0098459-g003\" target=\"_blank\">Figure 3B</a>. (<b>C</b>) Cells were incubated with TNFα in the presence or absence of graded concentrations of the NO donor, detaNO, followed by measurement of MTG fluorescence. Differing letters denote significant dose-dependent differences (p<0.05). Experiment was repeated 4 times. (<b>D</b>) Upper panel: western blot of HMEC-1 total eNOS expression, 48 h after transfection with either morpholino eNOS antisense (NOS3) or invert control (SON3) oligonucleotides. Lower panel: MTG fluorescence in cells treated with TNFα±Ado in either non-transfected cells or cells transfected with control or eNOS antisense morpholino oligos. Experiment was repeated 4 times per group, differing letters denote significant between-group differences (p<0.01).</p>", "links"=>[], "tags"=>["anatomy", "biological tissue", "epithelium", "Epithelial cells", "Endothelial cells", "Biochemistry", "Bioenergetics", "Energy-producing organelles", "Neurochemistry", "Neurochemicals", "Nitric oxide", "cell biology", "Cell processes", "Cell death", "Cellular types", "Molecular cell biology", "genetics", "epigenetics", "RNA interference", "gene expression", "neuroscience", "cardiology", "adenosine", "mediated"], "article_id"=>1051993, "categories"=>["Biological Sciences"], "users"=>["Theodore J. Kalogeris", "Christopher Baines", "Ronald J. Korthuis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0098459.g004", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_adenosine_Ado_is_mediated_by_eNOS_NO_dependent_mechanism_/1051993", "title"=>"Effect of adenosine (Ado) is mediated by eNOS/NO-dependent mechanism.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-10 02:49:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1528443"], "description"=>"<p>HMEC were plated in 6-well plates, then treated for 48 h as described for Fig. 4. Prior to treatment, some cells were transfected with morpholino-antisense or control oligos. Cells were washed free of media then loaded in the dark for 30 min with DAF-FM diacetate (5 µM) in HBSS+10 mM HEPES. Cells were further washed free of DAF-FM-containing buffer, and incubated a further 15 min. They were then gently scraped form the plate and separate aliquots were taken for assay of fluorescence and protein content. All fluorescence measurements were normalized to protein concentration, and the percent change in cellular fluorescence was calculated. Values are means ± S.E.M. for 4 separate experiments of 3 replicates each for each experimental condition except NOS3 (eNOS antisense) + detaNO for which data are for 3 separate experiments. Differing letters denote significant, between-group differences, p<0.05.</p>", "links"=>[], "tags"=>["anatomy", "biological tissue", "epithelium", "Epithelial cells", "Endothelial cells", "Biochemistry", "Bioenergetics", "Energy-producing organelles", "Neurochemistry", "Neurochemicals", "Nitric oxide", "cell biology", "Cell processes", "Cell death", "Cellular types", "Molecular cell biology", "genetics", "epigenetics", "RNA interference", "gene expression", "neuroscience", "cardiology", "decreases", "reversal", "adenosine"], "article_id"=>1051994, "categories"=>["Biological Sciences"], "users"=>["Theodore J. Kalogeris", "Christopher Baines", "Ronald J. Korthuis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0098459.g005", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TNF_945_decreases_cell_NO_and_reversal_of_this_effect_by_adenosine_is_eNOS_dependent_/1051994", "title"=>"TNFα decreases cell NO, and reversal of this effect by adenosine is eNOS-dependent.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-10 02:49:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1528445"], "description"=>"<p>Both sets of experiments (A, B) were repeated 3 times. (<b>A</b>) Cells in 100 cm dishes were incubated for 48 h with TNFα±Ado, in the presence or absence of sGC inhibitor, ODQ (30 µM), sGC agonist, YC-1 (100 µM) or cGMP analog, 8-Br-cGMP (500 µM). Mitochondrial mass measured using MTG fluorescence. Differing letters denote significant between-group differences, p<0.01. (<b>B</b>) Cells (non-transfected, or transfected with NOS3 or SON3 morpholino oligos to eNOS) were incubated for 48 h with TNFα±detaNO (100 nM) in the presence or absence of ODQ, YC-1, or 8-Br-cGMP, then MTG fluorescence was measured. Differeing letters denote significant between-group differences, p<0.05.</p>", "links"=>[], "tags"=>["anatomy", "biological tissue", "epithelium", "Epithelial cells", "Endothelial cells", "Biochemistry", "Bioenergetics", "Energy-producing organelles", "Neurochemistry", "Neurochemicals", "Nitric oxide", "cell biology", "Cell processes", "Cell death", "Cellular types", "Molecular cell biology", "genetics", "epigenetics", "RNA interference", "gene expression", "neuroscience", "cardiology", "mediated"], "article_id"=>1051996, "categories"=>["Biological Sciences"], "users"=>["Theodore J. Kalogeris", "Christopher Baines", "Ronald J. Korthuis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0098459.g006", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_adenosine_NO_is_mediated_by_a_sGC_cGMP_dependent_mechanism_/1051996", "title"=>"Effect of adenosine/NO is mediated by a sGC/cGMP-dependent mechanism.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-10 02:49:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1528446"], "description"=>"<p>(<b>A</b>) Western blot of expression of PGC-1α, Nrf-2, eNOS, and GAPDH, 48 h after transfection with either control or PGC-1α-specific siRNA. (<b>B</b>) Western blot of PGC-1α expression in response to TNFα±Ado or detaNO in either non-transfected cells, or cells transfected with either control (SON3) or eNOS antisense (NOS3) morpholino oligonucleotides. Blot shown is representative of 3 separate experiments. (<b>C</b>) MTG fluorescence after 48 h incubation with TNFα±Ado, detaNO, or 8-Br-cGMP in either control or PGC-1α siRNA-transfected cells (PGC siRNA). Data are from 4 separate experiments for reach group, differing letters denote significant between-group differences, p<0.05. (<b>D</b>) Measurement of Ψ in HMEC-1 cells in 24-well plates, treated as indicated, then loaded with TMRM or MTG dyes, as described in Methods. Data are means ± SEM for 4 replicates for each treatment/time combination, repeated 3 separate times. Asterisks denote values significantly different from control value, *: P<0.05, **: p<0.01.</p>", "links"=>[], "tags"=>["anatomy", "biological tissue", "epithelium", "Epithelial cells", "Endothelial cells", "Biochemistry", "Bioenergetics", "Energy-producing organelles", "Neurochemistry", "Neurochemicals", "Nitric oxide", "cell biology", "Cell processes", "Cell death", "Cellular types", "Molecular cell biology", "genetics", "epigenetics", "RNA interference", "gene expression", "neuroscience", "cardiology", "mediated"], "article_id"=>1051997, "categories"=>["Biological Sciences"], "users"=>["Theodore J. Kalogeris", "Christopher Baines", "Ronald J. Korthuis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0098459.g007", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_adenosine_NO_are_mediated_by_a_PGC_1_945_dependent_mechanisim_/1051997", "title"=>"Effects of adenosine/NO are mediated by a PGC-1α-dependent mechanisim.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-10 02:49:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1528447"], "description"=>"<p>Indicated treatments were as described for other figures. Values are means ± SEM of 4 separate experiments per treatment except for NOS3/SON3 where n = 5 and PGC-1α/Control siRNA where n = 3. Differing letters denote significant between-group differences.</p>", "links"=>[], "tags"=>["anatomy", "biological tissue", "epithelium", "Epithelial cells", "Endothelial cells", "Biochemistry", "Bioenergetics", "Energy-producing organelles", "Neurochemistry", "Neurochemicals", "Nitric oxide", "cell biology", "Cell processes", "Cell death", "Cellular types", "Molecular cell biology", "genetics", "epigenetics", "RNA interference", "gene expression", "neuroscience", "cardiology", "studies", "treatments", "mtg"], "article_id"=>1051998, "categories"=>["Biological Sciences"], "users"=>["Theodore J. Kalogeris", "Christopher Baines", "Ronald J. Korthuis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0098459.g008", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Control_studies_of_effect_of_individual_treatments_48_h_on_MTG_fluorescence_/1051998", "title"=>"Control studies of effect of individual treatments (48 h) on MTG fluorescence.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-10 02:49:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1528448"], "description"=>"<p>(<b>A</b>) Apoptosis assayed by counting of DAPI-stained cells on glass coverslips after 72 h incubation with TNFα±Ado or detaNO in either control or PGC-1α siRNA-transfected cells (PGC siRNA). Differing letters denote significant between-group differences, experiment was repeated 3 times. (<b>B</b>) Western blot of expression of cleaved (activated) caspase-3 in cells treated similarly as in panel (A).</p>", "links"=>[], "tags"=>["anatomy", "biological tissue", "epithelium", "Epithelial cells", "Endothelial cells", "Biochemistry", "Bioenergetics", "Energy-producing organelles", "Neurochemistry", "Neurochemicals", "Nitric oxide", "cell biology", "Cell processes", "Cell death", "Cellular types", "Molecular cell biology", "genetics", "epigenetics", "RNA interference", "gene expression", "neuroscience", "cardiology", "hmec-1", "cells", "tnf-induced", "apoptosis", "adenosine", "detano"], "article_id"=>1051999, "categories"=>["Biological Sciences"], "users"=>["Theodore J. Kalogeris", "Christopher Baines", "Ronald J. Korthuis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0098459.g009", "stats"=>{"downloads"=>2, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Protection_of_HMEC_1_cells_from_TNF_induced_apoptosis_by_adenosine_or_detaNO_is_dependent_on_PGC_1_945_/1051999", "title"=>"Protection of HMEC-1 cells from TNF-induced apoptosis by adenosine or detaNO is dependent on PGC-1α.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-10 02:49:58"}

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Relative Metric

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