Transcutaneous Application of Carbon Dioxide (CO2) Induces Mitochondrial Apoptosis in Human Malignant Fibrous Histiocytoma In Vivo
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{"title"=>"Transcutaneous Application of Carbon Dioxide (CO2) Induces Mitochondrial Apoptosis in Human Malignant Fibrous Histiocytoma In Vivo", "type"=>"journal", "authors"=>[{"first_name"=>"Yasuo", "last_name"=>"Onishi", "scopus_author_id"=>"22635830000"}, {"first_name"=>"Teruya", "last_name"=>"Kawamoto", "scopus_author_id"=>"7201664292"}, {"first_name"=>"Takeshi", "last_name"=>"Ueha", "scopus_author_id"=>"40361605000"}, {"first_name"=>"Kenta", "last_name"=>"Kishimoto", "scopus_author_id"=>"13403192500"}, {"first_name"=>"Hitomi", "last_name"=>"Hara", "scopus_author_id"=>"23392351000"}, {"first_name"=>"Naomasa", "last_name"=>"Fukase", "scopus_author_id"=>"18436678800"}, {"first_name"=>"Mitsunori", "last_name"=>"Toda", "scopus_author_id"=>"53265065900"}, {"first_name"=>"Risa", "last_name"=>"Harada", "scopus_author_id"=>"55237730800"}, {"first_name"=>"Masaya", "last_name"=>"Minoda", "scopus_author_id"=>"42262364400"}, {"first_name"=>"Yoshitada", "last_name"=>"Sakai", "scopus_author_id"=>"26028456600"}, {"first_name"=>"Masahiko", "last_name"=>"Miwa", "scopus_author_id"=>"8980021800"}, {"first_name"=>"Masahiro", "last_name"=>"Kurosaka", "scopus_author_id"=>"7006134457"}, {"first_name"=>"Toshihiro", "last_name"=>"Akisue", "scopus_author_id"=>"7003544655"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203 (Electronic)\r1932-6203 (Linking)", "pmid"=>"23166610", "doi"=>"10.1371/journal.pone.0049189", "pui"=>"366057678", "issn"=>"19326203", "sgr"=>"84869207386", "scopus"=>"2-s2.0-84869207386"}, "id"=>"cba7bee1-ab30-3829-ad08-e1bbe22269db", "abstract"=>"Mitochondria play an essential role in cellular energy metabolism and apoptosis. Previous studies have demonstrated that decreased mitochondrial biogenesis is associated with cancer progression. In mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) regulates the activities of multiple nuclear receptors and transcription factors involved in mitochondrial proliferation. Previously, we showed that overexpression of PGC-1α leads to mitochondrial proliferation and induces apoptosis in human malignant fibrous histiocytoma (MFH) cells in vitro. We also demonstrated that transcutaneous application of carbon dioxide (CO(2)) to rat skeletal muscle induces PGC-1α expression and causes an increase in mitochondrial proliferation. In this study, we utilized a murine model of human MFH to determine the effect of transcutaneous CO(2) exposure on PGC-1α expression, mitochondrial proliferation and cellular apoptosis. PGC-1α expression was evaluated by quantitative real-time PCR, while mitochondrial proliferation was assessed by immunofluorescence staining and the relative copy number of mitochondrial DNA (mtDNA) was assessed by real-time PCR. Immunofluorescence staining and DNA fragmentation assays were used to examine mitochondrial apoptosis. We also evaluated the expression of mitochondrial apoptosis related proteins, such as caspases, cytochorome c and Bax, by immunoblot analysis. We show that transcutaneous application of CO(2) induces PGC-1α expression, and increases mitochondrial proliferation and apoptosis of tumor cells, significantly reducing tumor volume. Proteins involved in the mitochondrial apoptotic cascade, including caspase 3 and caspase 9, were elevated in CO(2) treated tumors compared to control. We also observed an enrichment of cytochrome c in the cytoplasmic fraction and Bax protein in the mitochondrial fraction of CO(2) treated tumors, highlighting the involvement of mitochondria in apoptosis. These data indicate that transcutaneous application of CO(2) may represent a novel therapeutic tool in the treatment of human MFH.", "link"=>"http://www.mendeley.com/research/transcutaneous-application-carbon-dioxide-co2-induces-mitochondrial-apoptosis-human-malignant-fibrou-2", "reader_count"=>7, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Postgraduate"=>1, "Student > Master"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Postgraduate"=>1, "Student > Master"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/542120"], "description"=>"<p>Implanted tumors were isolated from mice at 0 (n = 12), 6 (n = 6) and 24 hours (n = 12) after transcutaneous CO<sub>2</sub> exposure, and the intracellular Ca<sup>2+</sup> concentration was assessed using the Calcium Assay Kit. Data represent the mean ± S.E. of at least three independent experiments (*<i>p</i><0.05, **<i>p</i><0.01).</p>", "links"=>[], "tags"=>["transcutaneous", "intracellular"], "article_id"=>212603, "categories"=>["Cancer", "Cell Biology"], "users"=>["Yasuo Onishi", "Teruya Kawamoto", "Takeshi Ueha", "Kenta Kishimoto", "Hitomi Hara", "Naomasa Fukase", "Mitsunori Toda", "Risa Harada", "Masaya Minoda", "Yoshitada Sakai", "Masahiko Miwa", "Masahiro Kurosaka", "Toshihiro Akisue"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049189.g004", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_transcutaneous_CO_2_application_on_intracellular_Ca_2_concentration_in_a_mouse_model_of_human_MFH_/212603", "title"=>"Effect of transcutaneous CO<sub>2</sub> application on intracellular Ca<sup>2+</sup> concentration in a mouse model of human MFH.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-15 00:43:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/290203", "https://ndownloader.figshare.com/files/290310", "https://ndownloader.figshare.com/files/290393"], "description"=>"<div><p>Mitochondria play an essential role in cellular energy metabolism and apoptosis. Previous studies have demonstrated that decreased mitochondrial biogenesis is associated with cancer progression. In mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) regulates the activities of multiple nuclear receptors and transcription factors involved in mitochondrial proliferation. Previously, we showed that overexpression of PGC-1α leads to mitochondrial proliferation and induces apoptosis in human malignant fibrous histiocytoma (MFH) cells <em>in vitro</em>. We also demonstrated that transcutaneous application of carbon dioxide (CO<sub>2</sub>) to rat skeletal muscle induces PGC-1α expression and causes an increase in mitochondrial proliferation. In this study, we utilized a murine model of human MFH to determine the effect of transcutaneous CO<sub>2</sub> exposure on PGC-1α expression, mitochondrial proliferation and cellular apoptosis. PGC-1α expression was evaluated by quantitative real-time PCR, while mitochondrial proliferation was assessed by immunofluorescence staining and the relative copy number of mitochondrial DNA (mtDNA) was assessed by real-time PCR. Immunofluorescence staining and DNA fragmentation assays were used to examine mitochondrial apoptosis. We also evaluated the expression of mitochondrial apoptosis related proteins, such as caspases, cytochorome c and Bax, by immunoblot analysis. We show that transcutaneous application of CO<sub>2</sub> induces PGC-1α expression, and increases mitochondrial proliferation and apoptosis of tumor cells, significantly reducing tumor volume. Proteins involved in the mitochondrial apoptotic cascade, including caspase 3 and caspase 9, were elevated in CO<sub>2</sub> treated tumors compared to control. We also observed an enrichment of cytochrome c in the cytoplasmic fraction and Bax protein in the mitochondrial fraction of CO<sub>2</sub> treated tumors, highlighting the involvement of mitochondria in apoptosis. These data indicate that transcutaneous application of CO<sub>2</sub> may represent a novel therapeutic tool in the treatment of human MFH.</p> </div>", "links"=>[], "tags"=>["transcutaneous", "carbon", "dioxide", "induces", "mitochondrial", "apoptosis", "malignant", "fibrous", "histiocytoma"], "article_id"=>117140, "categories"=>["Cancer", "Cell Biology"], "users"=>["Yasuo Onishi", "Teruya Kawamoto", "Takeshi Ueha", "Kenta Kishimoto", "Hitomi Hara", "Naomasa Fukase", "Mitsunori Toda", "Risa Harada", "Masaya Minoda", "Yoshitada Sakai", "Masahiko Miwa", "Masahiro Kurosaka", "Toshihiro Akisue"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0049189.s001", "https://dx.doi.org/10.1371/journal.pone.0049189.s002", "https://dx.doi.org/10.1371/journal.pone.0049189.s003"], "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Transcutaneous_Application_of_Carbon_Dioxide_CO_2_Induces_Mitochondrial_Apoptosis_in_Human_Malignant_Fibrous_Histiocytoma_In_Vivo__/117140", "title"=>"Transcutaneous Application of Carbon Dioxide (CO<sub>2</sub>) Induces Mitochondrial Apoptosis in Human Malignant Fibrous Histiocytoma <em>In Vivo</em>", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-11-15 01:59:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/541609"], "description"=>"<p>Mice were treated with CO<sub>2</sub> or control air three days after MFH cell implantation. Treatment was administered twice weekly for two weeks. (A) MFH tumors in CO<sub>2</sub> treated and control mice, two weeks post-implantation. (B) Tumor volume (mm<sup>3</sup>) in CO<sub>2</sub> treated or control mice was monitored for two weeks post-implantation. (C) Body weight (g) of CO<sub>2</sub> treated or control mice was monitored for two weeks post-implantation. Data represent the mean ± S.E of at least three independent experiments (*<i>p</i><0.05, **<i>p</i><0.01).</p>", "links"=>[], "tags"=>["transcutaneous", "mfh"], "article_id"=>212089, "categories"=>["Cancer", "Cell Biology"], "users"=>["Yasuo Onishi", "Teruya Kawamoto", "Takeshi Ueha", "Kenta Kishimoto", "Hitomi Hara", "Naomasa Fukase", "Mitsunori Toda", "Risa Harada", "Masaya Minoda", "Yoshitada Sakai", "Masahiko Miwa", "Masahiro Kurosaka", "Toshihiro Akisue"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049189.g001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_transcutaneous_application_of_CO_2_on_MFH_cell_growth_in_vivo_/212089", "title"=>"Effect of transcutaneous application of CO<sub>2</sub> on MFH cell growth <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-15 00:34:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/541966"], "description"=>"<p>(A) DNA fragmentation analysis of tumor samples from CO<sub>2</sub> treated and control mice two weeks post-treatment by immunofluorescence. (<i>Blue</i>, nuclear; <i>Green</i>, apoptosis nuclear) (B) DNA fragmentation was assessed by flow cytometry in CO<sub>2</sub> treated tumors (<i>Blue dots</i>) and control tumors (<i>Red</i>) two weeks post-treatment. (C) Immunoblot analyses determined that increased expression of the cleavage products of caspase 3 and 9, and PARP occurred in the CO<sub>2</sub> treated tumors compared to the control tumors. Tubulin was used as an endogenous loading control. (D) Immunoblot analysis of cytochrome c and Bax in mitochondrial and cytoplasmic fractions of CO<sub>2</sub> treated and control tumors. Tubulin was used as an endogenous loading control. (C, D) Positive bands in immunoblot analyses were semiquantified using densitometrical analyses using the Image J program (NIH, USA, <a href=\"http://rsb.info.nih.gov/ij/\" target=\"_blank\">http://rsb.info.nih.gov/ij/</a>).</p>", "links"=>[], "tags"=>["mitochondrial", "induced", "apoptosis", "treated"], "article_id"=>212450, "categories"=>["Cancer", "Cell Biology"], "users"=>["Yasuo Onishi", "Teruya Kawamoto", "Takeshi Ueha", "Kenta Kishimoto", "Hitomi Hara", "Naomasa Fukase", "Mitsunori Toda", "Risa Harada", "Masaya Minoda", "Yoshitada Sakai", "Masahiko Miwa", "Masahiro Kurosaka", "Toshihiro Akisue"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049189.g003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evaluation_of_mitochondrial_induced_apoptosis_in_CO_2_or_control_treated_tumors_/212450", "title"=>"Evaluation of mitochondrial induced apoptosis in CO<sub>2</sub> or control treated tumors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-15 00:40:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/541770"], "description"=>"<p>qRT-PCR for <i>PGC-1α</i> (A) and <i>TFAM</i> (B) in CO<sub>2</sub> treated or control tumor specimens collected two weeks post-treatment. Expression was normalized to <i>β-actin</i> control. Data represent the mean ± S.E of at least three independent experiments (*<i>p</i><0.05). (C) mtDNA was measured in CO<sub>2</sub> treated or control tumor samples by PCR and the relative copy number was determined by normalizing to nDNA. Data represent the mean ± S.E. of at least three independent experiments (*<i>p</i><0.05). (D) Immunofluorescence staining of mitochondria in CO<sub>2</sub> treated or control tumors after two weeks (<i>Blue</i>, nuclear; <i>Red</i>, mitochondria).</p>", "links"=>[], "tags"=>["transcutaneous", "mitochondrial", "proliferation"], "article_id"=>212255, "categories"=>["Cancer", "Cell Biology"], "users"=>["Yasuo Onishi", "Teruya Kawamoto", "Takeshi Ueha", "Kenta Kishimoto", "Hitomi Hara", "Naomasa Fukase", "Mitsunori Toda", "Risa Harada", "Masaya Minoda", "Yoshitada Sakai", "Masahiko Miwa", "Masahiro Kurosaka", "Toshihiro Akisue"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049189.g002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_transcutaneous_application_of_CO_2_treatment_on_mitochondrial_proliferation_in_tumors_/212255", "title"=>"Effect of transcutaneous application of CO<sub>2</sub> treatment on mitochondrial proliferation in tumors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-15 00:37:35"}

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Relative Metric

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