Mitochondrial DNA 10609T Promotes Hypoxia-Induced Increase of Intracellular ROS and Is a Risk Factor of High Altitude Polycythemia
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{"title"=>"Mitochondrial DNA 10609T promotes hypoxia-induced increase of intracellular ROS and is a risk factor of high altitude polycythemia", "type"=>"journal", "authors"=>[{"first_name"=>"Chunhua", "last_name"=>"Jiang", "scopus_author_id"=>"7403665903"}, {"first_name"=>"Jianhua", "last_name"=>"Cui", "scopus_author_id"=>"7401811734"}, {"first_name"=>"Fuyu", "last_name"=>"Liu", "scopus_author_id"=>"7406212520"}, {"first_name"=>"Liang", "last_name"=>"Gao", "scopus_author_id"=>"55368696100"}, {"first_name"=>"Yongjun", "last_name"=>"Luo", "scopus_author_id"=>"35218174100"}, {"first_name"=>"Peng", "last_name"=>"Li", "scopus_author_id"=>"56156839300"}, {"first_name"=>"Libin", "last_name"=>"Guan", "scopus_author_id"=>"55229106600"}, {"first_name"=>"Yuqi", "last_name"=>"Gao", "scopus_author_id"=>"35309941600"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pmid"=>"24498190", "pui"=>"373070856", "scopus"=>"2-s2.0-84900428689", "doi"=>"10.1371/journal.pone.0087775", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"84900428689"}, "id"=>"69e057de-09b9-3aef-a199-80371347fce3", "abstract"=>"Hypobaric hypoxia is the primary cause of high altitude polycythemia (HAPC). Mitochondria are critical organelles that consume high levels of oxygen and generate ATP. We hypothesize that the mitochondrion may be at the center of HAPC, and mitochondrial DNA (mtDNA) SNPs may be involved in its development. First, we conducted a case-control study to investigate the association of mtDNA variants with HAPC in Han Chinese migrating to the Qinghai-Tibetan Plateau. Pearson's chi-square tests revealed that mtDNA 8414T (MU) frequency (19.5%) in the HAPC group was significantly higher than that of the control (13.0%, P = 0.04, OR = 1.615, 95%CI: 1.020-2.555). The multivariate logistic regression analysis, after adjustment for environmental factors, revealed that mtDNA 10609T (WT) was significantly associated with an increased risk of HAPC (P<0.01, OR = 2.558, 95%CI: 1.250-5.236). Second, to verify the association, in vitro experiments of transmitochondrial cybrids was performed and revealed that the mtDNA 10609 variant promoted hypoxia-induced increase of intracellular ROS, but the mtDNA 8414 variant did not. Our findings provide evidence that, in Han Chinese, mtDNA 10609T promotes hypoxia-induced increase of intracellular ROS and is a HAPC risk factor.", "link"=>"http://www.mendeley.com/research/mitochondrial-dna-10609t-promotes-hypoxiainduced-increase-intracellular-ros-risk-factor-high-altitud", "reader_count"=>8, "reader_count_by_academic_status"=>{"Researcher"=>2, "Student > Ph. D. Student"=>1, "Other"=>3, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>2, "Student > Ph. D. Student"=>1, "Other"=>3, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>1, "Agricultural and Biological Sciences"=>3, "Social Sciences"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1368951", "https://ndownloader.figshare.com/files/1368952", "https://ndownloader.figshare.com/files/1368953", "https://ndownloader.figshare.com/files/1368954", "https://ndownloader.figshare.com/files/1368955"], "description"=>"<div><p>Hypobaric hypoxia is the primary cause of high altitude polycythemia (HAPC). Mitochondria are critical organelles that consume high levels of oxygen and generate ATP. We hypothesize that the mitochondrion may be at the center of HAPC, and mitochondrial DNA (mtDNA) SNPs may be involved in its development. First, we conducted a case-control study to investigate the association of mtDNA variants with HAPC in Han Chinese migrating to the Qinghai-Tibetan Plateau. Pearson’s chi-square tests revealed that mtDNA 8414T (MU) frequency (19.5%) in the HAPC group was significantly higher than that of the control (13.0%, P = 0.04, OR = 1.615, 95%CI: 1.020–2.555). The multivariate logistic regression analysis, after adjustment for environmental factors, revealed that mtDNA 10609T (WT) was significantly associated with an increased risk of HAPC (P<0.01, OR = 2.558, 95%CI: 1.250–5.236). Second, to verify the association, <i>in vitro</i> experiments of transmitochondrial cybrids was performed and revealed that the mtDNA 10609 variant promoted hypoxia-induced increase of intracellular ROS, but the mtDNA 8414 variant did not. Our findings provide evidence that, in Han Chinese, mtDNA 10609T promotes hypoxia-induced increase of intracellular ROS and is a HAPC risk factor.</p></div>", "links"=>[], "tags"=>["Biochemistry", "Bioenergetics", "Energy-producing organelles", "cytochemistry", "organelles", "Nucleic acids", "dna", "genetics", "population genetics", "Genetic polymorphism", "Molecular cell biology", "Cellular structures", "Subcellular organelles", "Population biology", "Clinical genetics", "Mitochondrial diseases", "hematology", "hematopoiesis", "10609t", "hypoxia-induced", "intracellular", "ros", "altitude"], "article_id"=>919948, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Chunhua Jiang", "Jianhua Cui", "Fuyu Liu", "Liang Gao", "Yongjun Luo", "Peng Li", "Libin Guan", "Yuqi Gao"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0087775.s001", "https://dx.doi.org/10.1371/journal.pone.0087775.s002", "https://dx.doi.org/10.1371/journal.pone.0087775.s003", "https://dx.doi.org/10.1371/journal.pone.0087775.s004", "https://dx.doi.org/10.1371/journal.pone.0087775.s005"], "stats"=>{"downloads"=>15, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mitochondrial_DNA_10609T_Promotes_Hypoxia_Induced_Increase_of_Intracellular_ROS_and_Is_a_Risk_Factor_of_High_Altitude_Polycythemia_/919948", "title"=>"Mitochondrial DNA 10609T Promotes Hypoxia-Induced Increase of Intracellular ROS and Is a Risk Factor of High Altitude Polycythemia", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-01-30 04:30:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1368948"], "description"=>"<p>Data are presented as mean ± SD. Hb = hemoglobin; EPO = erythropoietin; ROS = reactive oxygen species; BMI = body mass index.</p>*<p>compared with the control group = P<0.05;</p>**<p>compared with the control group = P<0.01.</p>", "links"=>[], "tags"=>["Biochemistry", "Bioenergetics", "Energy-producing organelles", "cytochemistry", "organelles", "Nucleic acids", "dna", "genetics", "population genetics", "Genetic polymorphism", "Molecular cell biology", "Cellular structures", "Subcellular organelles", "Population biology", "Clinical genetics", "Mitochondrial diseases", "hematology", "hematopoiesis", "physiological", "indices"], "article_id"=>919945, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Chunhua Jiang", "Jianhua Cui", "Fuyu Liu", "Liang Gao", "Yongjun Luo", "Peng Li", "Libin Guan", "Yuqi Gao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087775.t002", "stats"=>{"downloads"=>3, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Assessment_of_basic_physiological_indices_in_the_study_population_/919945", "title"=>"Assessment of basic physiological indices in the study population.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-01-30 04:30:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1368946"], "description"=>"*<p>compared with the control group = P<0.05.</p>", "links"=>[], "tags"=>["Biochemistry", "Bioenergetics", "Energy-producing organelles", "cytochemistry", "organelles", "Nucleic acids", "dna", "genetics", "population genetics", "Genetic polymorphism", "Molecular cell biology", "Cellular structures", "Subcellular organelles", "Population biology", "Clinical genetics", "Mitochondrial diseases", "hematology", "hematopoiesis", "mtdna", "variants", "hapc", "groups"], "article_id"=>919943, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Chunhua Jiang", "Jianhua Cui", "Fuyu Liu", "Liang Gao", "Yongjun Luo", "Peng Li", "Libin Guan", "Yuqi Gao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087775.t004", "stats"=>{"downloads"=>3, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Allele_frequency_of_mtDNA_variants_in_the_HAPC_and_control_groups_/919943", "title"=>"Allele frequency of mtDNA variants in the HAPC and control groups (%).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-01-30 04:30:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1368947"], "description"=>"<p>OR = odds ratio; CI = confidence interval.</p>a<p> = WT genotype is ref.</p>", "links"=>[], "tags"=>["Biochemistry", "Bioenergetics", "Energy-producing organelles", "cytochemistry", "organelles", "Nucleic acids", "dna", "genetics", "population genetics", "Genetic polymorphism", "Molecular cell biology", "Cellular structures", "Subcellular organelles", "Population biology", "Clinical genetics", "Mitochondrial diseases", "hematology", "hematopoiesis", "logistic", "regression", "hapc", "mtdna", "adjusted"], "article_id"=>919944, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Chunhua Jiang", "Jianhua Cui", "Fuyu Liu", "Liang Gao", "Yongjun Luo", "Peng Li", "Libin Guan", "Yuqi Gao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087775.t005", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Multiple_logistic_regression_analysis_of_the_relationship_between_HAPC_and_mtDNA_variants_adjusted_for_environmental_factors_/919944", "title"=>"Multiple logistic regression analysis of the relationship between HAPC and mtDNA variants, adjusted for environmental factors.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-01-30 04:30:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1368945"], "description"=>"<p>A. <i>qRT-PCR</i> analysis of mRNA level of EPO from 143B-10609T (WT) and 143B-10609C (MU) cultured for 12 h under hypoxic conditions (37°C, 5% carbon dioxide, and 3% oxygen) (n = 3). B. <i>qRT-PCR</i> analysis of mRNA level of EPO from 143B-10609T (WT) incubated in the absence or presence of 2.5 mM N-acetyl-L-cysteine (NAC) for 12 h under hypoxic conditions (37°C, 5% carbon dioxide, and 3% oxygen) (n = 3). Housekeeping gene was beta-actin, and the relative expression value was calculated by 2−ΔΔT method. Error bars indicate the standard deviation. * P<0.01; significantly different from 143B-10609C (MU). ΔP<0.05; significantly different from 143B-10609T (WT) incubated in the absence of 2.5 mM NAC.</p>", "links"=>[], "tags"=>["Biochemistry", "Bioenergetics", "Energy-producing organelles", "cytochemistry", "organelles", "Nucleic acids", "dna", "genetics", "population genetics", "Genetic polymorphism", "Molecular cell biology", "Cellular structures", "Subcellular organelles", "Population biology", "Clinical genetics", "Mitochondrial diseases", "hematology", "hematopoiesis", "mrna", "epo"], "article_id"=>919942, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Chunhua Jiang", "Jianhua Cui", "Fuyu Liu", "Liang Gao", "Yongjun Luo", "Peng Li", "Libin Guan", "Yuqi Gao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087775.g005", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_mRNA_level_of_EPO_in_cybrids_/919942", "title"=>"The mRNA level of EPO in cybrids.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-30 04:30:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1368942"], "description"=>"<p>Schematic of transmitochondrial cybrid generation for the mtDNA 10609 site.</p>", "links"=>[], "tags"=>["Biochemistry", "Bioenergetics", "Energy-producing organelles", "cytochemistry", "organelles", "Nucleic acids", "dna", "genetics", "population genetics", "Genetic polymorphism", "Molecular cell biology", "Cellular structures", "Subcellular organelles", "Population biology", "Clinical genetics", "Mitochondrial diseases", "hematology", "hematopoiesis", "transmitochondrial", "cybrid", "mtdna", "10609"], "article_id"=>919939, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Chunhua Jiang", "Jianhua Cui", "Fuyu Liu", "Liang Gao", "Yongjun Luo", "Peng Li", "Libin Guan", "Yuqi Gao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087775.g002", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_of_transmitochondrial_cybrid_generation_for_the_mtDNA_10609_site_/919939", "title"=>"Schematic of transmitochondrial cybrid generation for the mtDNA 10609 site.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-30 04:30:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1368941"], "description"=>"<p>Schematic of transmitochondrial cybrid generation for the mtDNA 8414 site.</p>", "links"=>[], "tags"=>["Biochemistry", "Bioenergetics", "Energy-producing organelles", "cytochemistry", "organelles", "Nucleic acids", "dna", "genetics", "population genetics", "Genetic polymorphism", "Molecular cell biology", "Cellular structures", "Subcellular organelles", "Population biology", "Clinical genetics", "Mitochondrial diseases", "hematology", "hematopoiesis", "transmitochondrial", "cybrid", "mtdna", "8414"], "article_id"=>919938, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Chunhua Jiang", "Jianhua Cui", "Fuyu Liu", "Liang Gao", "Yongjun Luo", "Peng Li", "Libin Guan", "Yuqi Gao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087775.g001", "stats"=>{"downloads"=>5, "page_views"=>176, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_of_transmitochondrial_cybrid_generation_for_the_mtDNA_8414_site_/919938", "title"=>"Schematic of transmitochondrial cybrid generation for the mtDNA 8414 site.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-30 04:30:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1368950"], "description"=>"<p>BMI = body mass index;</p>a<p> = <i>χ</i><sup>2</sup> test.</p>", "links"=>[], "tags"=>["Biochemistry", "Bioenergetics", "Energy-producing organelles", "cytochemistry", "organelles", "Nucleic acids", "dna", "genetics", "population genetics", "Genetic polymorphism", "Molecular cell biology", "Cellular structures", "Subcellular organelles", "Population biology", "Clinical genetics", "Mitochondrial diseases", "hematology", "hematopoiesis"], "article_id"=>919947, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Chunhua Jiang", "Jianhua Cui", "Fuyu Liu", "Liang Gao", "Yongjun Luo", "Peng Li", "Libin Guan", "Yuqi Gao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087775.t001", "stats"=>{"downloads"=>4, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characteristics_of_the_study_population_n_/919947", "title"=>"Characteristics of the study population. (n, %).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-01-30 04:30:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1368949"], "description"=>"<p>Hb = hemoglobin; EPO = erythropoietin;</p>a<p> = <i>t</i> test.</p>", "links"=>[], "tags"=>["Biochemistry", "Bioenergetics", "Energy-producing organelles", "cytochemistry", "organelles", "Nucleic acids", "dna", "genetics", "population genetics", "Genetic polymorphism", "Molecular cell biology", "Cellular structures", "Subcellular organelles", "Population biology", "Clinical genetics", "Mitochondrial diseases", "hematology", "hematopoiesis", "hapc", "mtdna"], "article_id"=>919946, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Chunhua Jiang", "Jianhua Cui", "Fuyu Liu", "Liang Gao", "Yongjun Luo", "Peng Li", "Libin Guan", "Yuqi Gao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087775.t003", "stats"=>{"downloads"=>5, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Initial_screening_of_potential_HAPC_associated_mtDNA_variants_/919946", "title"=>"Initial screening of potential HAPC associated mtDNA variants.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-01-30 04:30:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1368944"], "description"=>"<p>First, the normoxic and hypoxic cybrids were cultured in a normoxic incubator (37°C, 5% carbon dioxide, and 21% oxygen) for 48 hours. Second, hypoxic cybrids were shifted and cultured in a hypoxic incubator (37°C, 5% carbon dioxide, and 3% oxygen) for 12 hours. Normoxic cybrids were still cultured in the normoxic incubator for 12 hours. Finally, all of the cybrids were incubated with 2.5 mM DCFH-DA fluorescent probe. The average fluorescence intensity of the cybrids was measured by flow cytometry. The average fluorescence intensity reflected the level of intracellular ROS. All cultures were done in triplicate (n = 3). A. Intracellular ROS in 143B-8414C (WT) and 143B-8414T (MU) under normoxic and hypoxic conditions. B. Intracellular ROS in 143B-10609T (WT) and 143B-10609C (MU) under normoxic and hypoxic conditions. C. The increasing rate of intracellular ROS relative to normoxic conditions in the 143B-8414C (WT) and 143B-8414T (MU) cybrids. D. The increasing rate of intracellular ROS relative to normoxic conditions in the 143B-10609T (WT) and 143B-10609C (MU) cybrids. Error bars indicate the standard deviation. *P<0.05; significantly different from culture under 21% oxygen. ▴ P<0.05; significantly different from 143B-10609C (MU) cybrids.</p>", "links"=>[], "tags"=>["Biochemistry", "Bioenergetics", "Energy-producing organelles", "cytochemistry", "organelles", "Nucleic acids", "dna", "genetics", "population genetics", "Genetic polymorphism", "Molecular cell biology", "Cellular structures", "Subcellular organelles", "Population biology", "Clinical genetics", "Mitochondrial diseases", "hematology", "hematopoiesis", "ros", "cybrids", "normoxic", "hypoxic"], "article_id"=>919941, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Chunhua Jiang", "Jianhua Cui", "Fuyu Liu", "Liang Gao", "Yongjun Luo", "Peng Li", "Libin Guan", "Yuqi Gao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087775.g004", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Intracellular_ROS_in_the_cybrids_under_normoxic_and_hypoxic_conditions_/919941", "title"=>"Intracellular ROS in the cybrids under normoxic and hypoxic conditions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-30 04:30:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1368943"], "description"=>"<p>Identification of the transmitochondrial cybrids by PCR.</p>", "links"=>[], "tags"=>["Biochemistry", "Bioenergetics", "Energy-producing organelles", "cytochemistry", "organelles", "Nucleic acids", "dna", "genetics", "population genetics", "Genetic polymorphism", "Molecular cell biology", "Cellular structures", "Subcellular organelles", "Population biology", "Clinical genetics", "Mitochondrial diseases", "hematology", "hematopoiesis", "transmitochondrial", "cybrids"], "article_id"=>919940, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Chunhua Jiang", "Jianhua Cui", "Fuyu Liu", "Liang Gao", "Yongjun Luo", "Peng Li", "Libin Guan", "Yuqi Gao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087775.g003", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identification_of_the_transmitochondrial_cybrids_by_PCR_/919940", "title"=>"Identification of the transmitochondrial cybrids by PCR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-30 04:30:22"}

PMC Usage Stats | Further Information

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