Protective Effect of Hypercapnic Acidosis in Ischemia-Reperfusion Lung Injury Is Attributable to Upregulation of Heme Oxygenase-1
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{"title"=>"Protective Effect of Hypercapnic Acidosis in Ischemia-Reperfusion Lung Injury Is Attributable to Upregulation of Heme Oxygenase-1", "type"=>"journal", "authors"=>[{"first_name"=>"Shu Yu", "last_name"=>"Wu", "scopus_author_id"=>"55771414200"}, {"first_name"=>"Min Hui", "last_name"=>"Li", "scopus_author_id"=>"36071225100"}, {"first_name"=>"Fu Chang", "last_name"=>"Ko", "scopus_author_id"=>"23392548500"}, {"first_name"=>"Geng Chin", "last_name"=>"Wu", "scopus_author_id"=>"25627032700"}, {"first_name"=>"Kun Lun", "last_name"=>"Huang", "scopus_author_id"=>"55453803300"}, {"first_name"=>"Shi Jye", "last_name"=>"Chu", "scopus_author_id"=>"7403621864"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84883786177", "sgr"=>"84883786177", "doi"=>"10.1371/journal.pone.0074742", "issn"=>"19326203", "pui"=>"369796148", "pmid"=>"24040332"}, "id"=>"1a59cd96-e5e6-3a72-9f9f-6f1410517911", "abstract"=>"Hypercapnic acidosis (HCA) has protective effects in animal models of acute lung injury, but the mechanism underlying the effect of HCA is unclear. Heme oxygenase-1 (HO-1) is an antioxidant enzyme that protects tissue from inflammation injury. We investigated whether HO-1 contributes to the protective effects of HCA in ischemia-reperfusion (IR)-induced lung injury. Typical acute lung injury in rats was successfully induced by 40 min of ischemia and 90 min of reperfusion in an isolated perfused lung model. The rat lungs were randomly assigned to the control group, IR group or IR + HCA group with or without zinc protoporphyrin IX (ZnPP), an HO-1 activity inhibitor. At the end of the experiment, bronchoalveolar lavage fluid (BALF) and lung tissues were collected to evaluate the degree of lung injury. In in vitro experiments, HO-1 siRNA transfected A549 cells were exposed to a normoxic or hypoxia-reoxygenation (H/R) environment in the presence or absence of HCA. IR caused significant increases in the pulmonary arterial pressure, lung weight to body weight and wet/dry ratios, lung weight gain, capillary filtration coefficient, lung injury scores, neutrophil infiltration, and concentrations of protein and TNF-α in the BALF. IR also induced degradation of inhibitor of nuclear factor (NF)-κB-α, increased IκB kinase (IKK)-β phosphorylation and nuclear translocation of NF-κB, and up-regulated HO-1 expression and activity. Furthermore, IR decreased Bcl-2 protein expression and increased the number of active caspase-3 stained cells. HCA treatment enhanced HO-1 expression and activity, and accordingly reduced IKK-NF-κB signaling, inhibited apoptosis, and significantly attenuated IR-induced changes. Treatment with ZnPP partially blocked the protective effect of HCA. In addition, HO-1 siRNA significantly reversed HCA-mediated inhibition of NF-κB signaling in A549 cells subjected to H/R. In conclusion, the protective effect of HCA in IR lung injury in rats was mediated in part by the anti-inflammatory and anti-apoptotic action of HO-1.", "link"=>"http://www.mendeley.com/research/protective-effect-hypercapnic-acidosis-ischemiareperfusion-lung-injury-attributable-upregulation-hem", "reader_count"=>6, "reader_count_by_academic_status"=>{"Researcher"=>1, "Student > Ph. D. Student"=>4, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>1, "Student > Ph. D. Student"=>4, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Medicine and Dentistry"=>3, "Agricultural and Biological Sciences"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}}, "reader_count_by_country"=>{"United States"=>1, "Brazil"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1199179"], "description"=>"<p>Western blot and densitometry analysis were used for HO-1 protein expression (A). The induction of HO-1 protein by ischemia-reperfusion (IR) was accompanied by a marked increase in HO-1 activity (B). HCA further enhanced HO-1 protein expression and activity. ZnPP completely abolished HO-1 activity in either the absence or presence of HCA, although ZnPP also increased HO-1 protein expression. A representative blot is shown. Data are expressed as mean ± SD. *<i>P</i> < 0.05, ***<i>P</i> < 0.001, compared with control; <sup>+</sup><i>P</i> < 0.05, compared with IR-vehicle; <sup>#</sup><i>P</i> < 0.05, compared with IR+HCA, using one-way ANOVA with Bonferroni post-test.</p>", "links"=>[], "tags"=>["hca", "znpp", "ho-1"], "article_id"=>795454, "categories"=>["Biological Sciences"], "users"=>["Shu-Yu Wu", "Min-Hui Li", "Fu-Chang Ko", "Geng-Chin Wu", "Kun-Lun Huang", "Shi-Jye Chu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0074742.g001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_HCA_and_ZnPP_on_HO_1_protein_expression_and_activity_in_lung_tissue_/795454", "title"=>"Effect of HCA and ZnPP on HO-1 protein expression and activity in lung tissue.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-10 01:39:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1199190"], "description"=>"<p>Hypercapnic acidosis (HCA) increased the IκB-α level and reduced cytoplasmic phosphorylated IKK and nuclear NF-κB p65 levels in ischemia-reperfusion (IR)-induced lung injury. Zinc protoporphyrin IX (ZnPP) treatment partially attenuated the protective effect of HCA. TATA and β-actin served as loading controls for nuclear and cytoplasmic proteins, respectively. A representative blot is shown. Data are expressed as mean ± SD. *significantly different from control (<i>P</i> < 0.05); +significantly different from IR-vehicle (<i>P</i> < 0.05); <sup>#</sup> significantly different from IR+HCA (<i>P</i> < 0.05), using one-way ANOVA with Bonferroni post-test.</p>", "links"=>[], "tags"=>["hca", "znpp", "pathway"], "article_id"=>795465, "categories"=>["Biological Sciences"], "users"=>["Shu-Yu Wu", "Min-Hui Li", "Fu-Chang Ko", "Geng-Chin Wu", "Kun-Lun Huang", "Shi-Jye Chu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0074742.g006", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_HCA_and_ZnPP_for_IKK_NF_954_B_signaling_pathway_in_lung_tissue_/795465", "title"=>"Effect of HCA and ZnPP for IKK-NFκB signaling pathway in lung tissue.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-10 01:39:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1199187"], "description"=>"<p>(A) Western blot and densitometry analysis of Bcl-2 protein in lung tissue. β-actin served as a loading control for cytoplasmic proteins. A representative blot is shown. (B) Immunohistochemistry for active caspase-3 in the lung (200× magnification). Ischemia-reperfusion (IR) significantly decreased Bcl-2 protein expression and induced caspase-3 activation in the lung tissue. Hypercapnic acidosis (HCA) treatment significantly increased Bcl-2 protein expression and attenuated the signals for active caspase-3. When zinc protoporphyrin IX (ZnPP) was added, the protective effect was partially blocked. Data are expressed as mean ± D. *significantly different from control (<i>P</i> < 0.05); <sup>+</sup> significantly different from IR-vehicle (<i>P</i> < 0.05); <sup>#</sup> significantly different from IR+HCA (<i>P</i> < 0.05), using one-way ANOVA with Bonferroni post-test.</p>", "links"=>[], "tags"=>["hca", "znpp", "bcl-2", "caspase-3"], "article_id"=>795462, "categories"=>["Biological Sciences"], "users"=>["Shu-Yu Wu", "Min-Hui Li", "Fu-Chang Ko", "Geng-Chin Wu", "Kun-Lun Huang", "Shi-Jye Chu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0074742.g005", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_HCA_and_ZnPP_on_the_expression_of_Bcl_2_and_caspase_3_in_the_lung_/795462", "title"=>"Effect of HCA and ZnPP on the expression of Bcl-2 and caspase-3 in the lung.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-10 01:39:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1199184"], "description"=>"<p>As shown by a representative micrograph of lung tissue (400× magnification) (A), infiltrating neutrophils and septal widening were increased in the ischemia-reperfusion (IR) group. HCA treatment improved the histopathological changes, but the improvement was partially abolished by ZnPP treatment. The lung injury scores (B) and the numbers of neutrophils per high power field (400× magnification) (C) were significantly higher (<i>P</i> < 0.05) in the IR group than in the control group. HCA treatment significantly reduced the increase, but these improvements were partially abolished by ZnPP treatment. Data are expressed as mean ± SD. *significantly different from control (<i>P</i> < 0.05); +significantly different from IR-vehicle (<i>P</i> < 0.05); <sup>#</sup> significantly different from IR+HCA (<i>P</i> < 0.05), using one-way ANOVA with Bonferroni post-test.</p>", "links"=>[], "tags"=>["hca", "znpp", "histological"], "article_id"=>795459, "categories"=>["Biological Sciences"], "users"=>["Shu-Yu Wu", "Min-Hui Li", "Fu-Chang Ko", "Geng-Chin Wu", "Kun-Lun Huang", "Shi-Jye Chu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0074742.g004", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_HCA_and_ZnPP_on_the_histological_appearance_of_lung_tissue_/795459", "title"=>"Effect of HCA and ZnPP on the histological appearance of lung tissue.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-10 01:39:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1199195", "https://ndownloader.figshare.com/files/1199196"], "description"=>"<div><p>Hypercapnic acidosis (HCA) has protective effects in animal models of acute lung injury, but the mechanism underlying the effect of HCA is unclear. Heme oxygenase-1 (HO-1) is an antioxidant enzyme that protects tissue from inflammation injury. We investigated whether HO-1 contributes to the protective effects of HCA in ischemia-reperfusion (IR)-induced lung injury. Typical acute lung injury in rats was successfully induced by 40 min of ischemia and 90 min of reperfusion in an isolated perfused lung model. The rat lungs were randomly assigned to the control group, IR group or IR + HCA group with or without zinc protoporphyrin IX (ZnPP), an HO-1 activity inhibitor. At the end of the experiment, bronchoalveolar lavage fluid (BALF) and lung tissues were collected to evaluate the degree of lung injury. In <i>in vitro</i> experiments, HO-1 siRNA transfected A549 cells were exposed to a normoxic or hypoxia-reoxygenation (H/R) environment in the presence or absence of HCA. IR caused significant increases in the pulmonary arterial pressure, lung weight to body weight and wet/dry ratios, lung weight gain, capillary filtration coefficient, lung injury scores, neutrophil infiltration, and concentrations of protein and TNF-α in the BALF. IR also induced degradation of inhibitor of nuclear factor (NF)-κB-α, increased IκB kinase (IKK)-β phosphorylation and nuclear translocation of NF-κB, and up-regulated HO-1 expression and activity. Furthermore, IR decreased Bcl-2 protein expression and increased the number of active caspase-3 stained cells. HCA treatment enhanced HO-1 expression and activity, and accordingly reduced IKK-NF-κB signaling, inhibited apoptosis, and significantly attenuated IR-induced changes. Treatment with ZnPP partially blocked the protective effect of HCA. In addition, HO-1 siRNA significantly reversed HCA-mediated inhibition of NF-κB signaling in A549 cells subjected to H/R. In conclusion, the protective effect of HCA in IR lung injury in rats was mediated in part by the anti-inflammatory and anti-apoptotic action of HO-1.</p> </div>", "links"=>[], "tags"=>["hypercapnic", "acidosis", "ischemia-reperfusion", "attributable", "upregulation", "heme"], "article_id"=>795470, "categories"=>["Biological Sciences"], "users"=>["Shu-Yu Wu", "Min-Hui Li", "Fu-Chang Ko", "Geng-Chin Wu", "Kun-Lun Huang", "Shi-Jye Chu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0074742.s001", "https://dx.doi.org/10.1371/journal.pone.0074742.s002"], "stats"=>{"downloads"=>3, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Protective_Effect_of_Hypercapnic_Acidosis_in_Ischemia_Reperfusion_Lung_Injury_Is_Attributable_to_Upregulation_of_Heme_Oxygenase_1_/795470", "title"=>"Protective Effect of Hypercapnic Acidosis in Ischemia-Reperfusion Lung Injury Is Attributable to Upregulation of Heme Oxygenase-1", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-09-10 01:39:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1199192"], "description"=>"<p>(A) HO-1 siRNA significantly attenuated the protective effect of HCA which reduced the increase of phosphorylated NF-κB p65 (p-p65) at 4 h, and p-IKK at 2 h, and the degradation of IκB-α at 2 h in A549 cells exposed to H/R. (B) HO-1 siRNA blocked the decrease of CXCL8 production by HCA in H/R-exposed A549 cells. A representative blot is shown. Data are expressed as mean ± SD. *<i>P</i> < 0.05, **<i>P</i> < 0.01, <i>***P</i> < 0.001 versus 5% CO<sub>2</sub>; <sup># </sup><i>P</i> < 0.05, <i><sup># # #</sup> P</i> < 0.001 versus 10% CO<sub>2</sub>, using one-way ANOVA with Bonferroni post-test.</p>", "links"=>[], "tags"=>["hca", "ho-1", "sirna", "a549", "cells", "subjected", "hypoxia-reoxygenation"], "article_id"=>795467, "categories"=>["Biological Sciences"], "users"=>["Shu-Yu Wu", "Min-Hui Li", "Fu-Chang Ko", "Geng-Chin Wu", "Kun-Lun Huang", "Shi-Jye Chu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0074742.g007", "stats"=>{"downloads"=>3, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_HCA_and_HO_1_siRNA_in_A549_cells_subjected_to_hypoxia_reoxygenation_H_R_/795467", "title"=>"Effect of HCA and HO-1 siRNA in A549 cells subjected to hypoxia-reoxygenation (H/R).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-10 01:39:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1199182"], "description"=>"<p>The lung weight gain (A), K<sub>f</sub> (B), lung weight/body weight (LW/BW) (C) and wet/dry (W/D) weight ratios (D), protein concentration (E) and TNF-α level in the bronchoalveolar lavage fluid (F) increased significantly in the ischemia-reperfusion (IR) group. The increase in these parameters was significantly attenuated by treatment with HCA. The protective effect of HCA was partially abrogated by ZnPP treatment. Data are expressed as mean ± SD. *significantly different from control (<i>P</i> < 0.05); <sup>+</sup> significantly different from IR-vehicle (<i>P</i> < 0.05); <i><sup>#</sup></i> significantly different from IR+HCA (<i>P</i> < 0.05), using one-way or two-way ANOVA with Bonferroni post-test.</p>", "links"=>[], "tags"=>["hca", "znpp", "pulmonary", "edema", "bronchoalveolar", "lavage"], "article_id"=>795457, "categories"=>["Biological Sciences"], "users"=>["Shu-Yu Wu", "Min-Hui Li", "Fu-Chang Ko", "Geng-Chin Wu", "Kun-Lun Huang", "Shi-Jye Chu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0074742.g003", "stats"=>{"downloads"=>2, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_HCA_and_ZnPP_on_pulmonary_edema_and_TNF_945_level_in_bronchoalveolar_lavage_fluid_/795457", "title"=>"Effect of HCA and ZnPP on pulmonary edema and TNF-α level in bronchoalveolar lavage fluid.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-10 01:39:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1199180"], "description"=>"<p>The PAP increased significantly in the ischemia-reperfusion (IR) group. The increase in the PAP was attenuated significantly by treatment with HCA, but not when ZnPP was added. Data are expressed as mean ± SD. <sup>+</sup>significantly different from IR-vehicle (<i>P</i> < 0.05); <i><sup>#</sup></i> significantly different from IR+HCA (<i>P</i> < 0.05), using two-way ANOVA with Bonferroni post-test.</p>", "links"=>[], "tags"=>["hca", "znpp", "pulmonary", "artery"], "article_id"=>795455, "categories"=>["Biological Sciences"], "users"=>["Shu-Yu Wu", "Min-Hui Li", "Fu-Chang Ko", "Geng-Chin Wu", "Kun-Lun Huang", "Shi-Jye Chu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0074742.g002", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_HCA_and_ZnPP_on_pulmonary_artery_pressure_916_PAP_/795455", "title"=>"Effect of HCA and ZnPP on pulmonary artery pressure (ΔPAP).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-10 01:39:57"}

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Relative Metric

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