Decreased Reactive Oxygen Species Production in Cells with Mitochondrial Haplogroups Associated with Longevity
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{"title"=>"Decreased Reactive Oxygen Species Production in Cells with Mitochondrial Haplogroups Associated with Longevity", "type"=>"journal", "authors"=>[{"first_name"=>"Ai", "last_name"=>"Chen", "scopus_author_id"=>"50760911300"}, {"first_name"=>"Nicola", "last_name"=>"Raule", "scopus_author_id"=>"6507722492"}, {"first_name"=>"Anne", "last_name"=>"Chomyn", "scopus_author_id"=>"7004058145"}, {"first_name"=>"Giuseppe", "last_name"=>"Attardi", "scopus_author_id"=>"7102516458"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84868130688", "sgr"=>"84868130688", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0046473", "pmid"=>"23144696", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"365953182"}, "id"=>"f859983f-bfb1-3482-b85f-74d579902f4d", "abstract"=>"Mitochondrial DNA (mtDNA) is highly polymorphic, and its variations in humans may contribute to individual differences in function. Zhang and colleagues found a strikingly higher frequency of a C150T transition in the D-loop of mtDNA from centenarians and twins of an Italian population, and also demonstrated that this base substitution causes a remodeling of the mtDNA 151 replication origin in human leukocytes and fibroblasts [1]. The C150T transition is a polymorphism associated with several haplogroups. To determine whether haplogroups that carry the C150T transition display any phenotype that may be advantageous for longevity, we analyzed cybrids carrying or not the C150T transition. These cybrids were obtained by fusing cytoplasts derived from human fibroblasts with human mtDNA-less cells (ρ(0) cells). We chose for cybrid construction and analysis haplogroup-matched pairs of fibroblast strains containing or not the C150T transition. In particular, we used, as one pair of mtDNA donors, a fibroblast strain of the U3a haplogroup, carrying the C150T transition and a strain of the U-K2 haplogroup, without the C150T transition, and as another pair, fibroblasts of the J2b haplogroup, carrying the C150T transition and of the J1c haplogroup, without the C150T transition. We have found no association of respiratory capacity, mtDNA level, mitochondrial gene expression level, or growth rate with the presence of the C150T transition. However, we have found that the cybrids with haplogroups that include the C150T transition have in common a lower reactive oxygen species (ROS) production rate than the haplogroup-matched cybrids without that transition. Thus, the lower ROS production rate may be a factor in the increased longevity associated with the U and the J2 haplogroups. Of further interest, we found that cybrids with the U3a haplogroup exhibited a higher respiration rate than the other cybrids examined.", "link"=>"http://www.mendeley.com/research/decreased-reactive-oxygen-species-production-cells-mitochondrial-haplogroups-associated-longevity", "reader_count"=>27, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>2, "Student > Bachelor"=>2, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>2, "Student > Bachelor"=>2, "Professor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>7, "Nursing and Health Professions"=>1, "Medicine and Dentistry"=>4, "Agricultural and Biological Sciences"=>10, "Neuroscience"=>1, "Design"=>1, "Sports and Recreations"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>2}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Neuroscience"=>{"Neuroscience"=>1}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"United Kingdom"=>1, "Portugal"=>2}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/293960/Table_S1.docx"], "description"=>"<div><p>Mitochondrial DNA (mtDNA) is highly polymorphic, and its variations in humans may contribute to individual differences in function. Zhang and colleagues found a strikingly higher frequency of a C150T transition in the D-loop of mtDNA from centenarians and twins of an Italian population, and also demonstrated that this base substitution causes a remodeling of the mtDNA 151 replication origin in human leukocytes and fibroblasts <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046473#pone.0046473-Zhang1\">[1]</a>. The C150T transition is a polymorphism associated with several haplogroups. To determine whether haplogroups that carry the C150T transition display any phenotype that may be advantageous for longevity, we analyzed cybrids carrying or not the C150T transition. These cybrids were obtained by fusing cytoplasts derived from human fibroblasts with human mtDNA-less cells (ρ<sup>0</sup> cells). We chose for cybrid construction and analysis haplogroup-matched pairs of fibroblast strains containing or not the C150T transition. In particular, we used, as one pair of mtDNA donors, a fibroblast strain of the U3a haplogroup, carrying the C150T transition and a strain of the U-K2 haplogroup, without the C150T transition, and as another pair, fibroblasts of the J2b haplogroup, carrying the C150T transition and of the J1c haplogroup, without the C150T transition. We have found no association of respiratory capacity, mtDNA level, mitochondrial gene expression level, or growth rate with the presence of the C150T transition. However, we have found that the cybrids with haplogroups that include the C150T transition have in common a lower reactive oxygen species (ROS) production rate than the haplogroup-matched cybrids without that transition. Thus, the lower ROS production rate may be a factor in the increased longevity associated with the U and the J2 haplogroups. Of further interest, we found that cybrids with the U3a haplogroup exhibited a higher respiration rate than the other cybrids examined.</p> </div>", "links"=>[], "tags"=>["decreased", "reactive", "cells", "mitochondrial", "haplogroups", "longevity"], "article_id"=>117877, "categories"=>["Biochemistry", "Biological Sciences", "Cancer", "Genetics", "Biotechnology"], "users"=>["Ai Chen", "Nicola Raule", "Anne Chomyn", "Giuseppe Attardi"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0046473"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/Decreased_Reactive_Oxygen_Species_Production_in_Cells_with_Mitochondrial_Haplogroups_Associated_with_Longevity__/117877", "title"=>"Decreased Reactive Oxygen Species Production in Cells with Mitochondrial Haplogroups Associated with Longevity", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-10-29 02:11:17"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/551471/Figure_1.tif"], "description"=>"<p>The population doubling times during 7 days of growth are indicated. The cell lines are grouped by mtDNA donor cell and the haplogroup of the donor is indicated, namely U3a, U-K2, J2b, and J1c. The horizontal gray lines indicate the mean doubling time for each group of cybrids. A black horizontal line indicates that the difference between the doubling times of the cybrid groups at the ends of the line is significant. ** indicates P≤0.01, by the t-test.</p>", "links"=>[], "tags"=>["rates", "cybrid"], "article_id"=>221968, "categories"=>["Biochemistry", "Biological Sciences", "Cancer", "Genetics", "Biotechnology"], "users"=>["Ai Chen", "Nicola Raule", "Anne Chomyn", "Giuseppe Attardi"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0046473.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Growth_rates_of_cybrid_cell_lines_/221968", "title"=>"Growth rates of cybrid cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-10-29 00:32:48"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/551618/Figure_2.tif"], "description"=>"<p><b>A</b>, Electrophoretic patterns of the mitochondrial translation products of cybrid clones labeled for 45 min with [<sup>35</sup>S]methionine in the presence of 100 µg/ml of emetine. Each lane represents a different cybrid clone, the name of which is given below the corresponding bar in panel <b>B</b>. ND1, -2, -3, -4, -4L, -5, and -6, NADH dehydrogenase subunits 1, 2, 3, 4, 4L, 5, and 6, respectively; CYTb, apocytochrome <i>b</i>; COI, -II, and -III, subunits I, II, and III, respectively of cytochrome <i>c</i> oxidase; A6 and A8, subunits 6 and 8, respectively, of the H<sup>+</sup>-ATPase. <b>B</b>, Quantification of the labeling of the mitochondrial translation products shown in panel <b>A</b>. The cell lines are grouped by haplogroup, namely U3a, U-K2, J2b, and J1c. The horizontal gray lines in panel <b>B</b> indicate the mean level of labeling for each group of cybrids. Neither the difference between the U3a and the U-K2 cybrids nor the difference between the J2b and the J1c cybrids is statistically significant.</p>", "links"=>[], "tags"=>["synthesis"], "article_id"=>222116, "categories"=>["Biochemistry", "Biological Sciences", "Cancer", "Genetics", "Biotechnology"], "users"=>["Ai Chen", "Nicola Raule", "Anne Chomyn", "Giuseppe Attardi"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0046473.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Mitochondrial_protein_synthesis_rates_/222116", "title"=>"Mitochondrial protein synthesis rates.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-10-29 00:35:16"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/551737/Figure_3.tif"], "description"=>"<p><b>A</b>, Average rates of O<sub>2</sub> consumption in intact cells, normalized to protein concentration, in individual cybrid clones are shown. Cell lines are grouped by haplogroup. A total of 3–6 determinations were made on each of three or four cybrid clones of each haplogroup. The error bars indicate the standard error of the mean. The horizontal gray lines indicate the mean respiration rate for the haplogroup. The horizontal black bars with asterisk indicate that the difference between the indicated groups is statistically significant; *, P≤0.05; **, P<0.01. <b>B</b>, DNP-uncoupled endogenous oxygen consumption rates, normalized to protein concentration, were measured 3–6 times for each cybrid clone. The ratios of uncoupled to endogenous respiration rates are shown.</p>", "links"=>[], "tags"=>["genetics and genomics", "public health and epidemiology", "Computational biology", "oncology", "Biochemistry"], "article_id"=>222231, "categories"=>["Biochemistry", "Biological Sciences", "Cancer", "Genetics", "Biotechnology"], "users"=>["Ai Chen", "Nicola Raule", "Anne Chomyn", "Giuseppe Attardi"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0046473.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Respiration_rates_/222231", "title"=>"Respiration rates.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-10-29 00:37:11"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/551891/Figure_4.tif"], "description"=>"<p>The activities of the various components of the respiratory chain were investigated by measuring the respiration rate dependent on (<b>A</b>) malate plus glutamate, on (<b>B</b>) succinate plus G3P (in the presence of rotenone) and on (<b>C</b>) TMPD plus ascorbate (in the presence of antimycin). Cell lines are grouped by haplogroup. A total of 3–4 determinations were made on each of the three or four cybrid clones derived from each fibroblast strain. The mean of those determinations is shown. The error bars indicate the standard error of the mean. Horizontal gray lines represent the average for each haplogroup. Horizontal black bars with asterisks indicate differences between averages are statistically significant; *, P≤0.05; **, P<0.01. P = 0.0578 for the difference between the means of respiration rate of the J2b and the J1c cybrids in panel <b>A</b>, i.e. not quite statistically significant.</p>", "links"=>[], "tags"=>["digitonin-permeabilized", "cells", "cybrid", "clones", "substrates"], "article_id"=>222379, "categories"=>["Biochemistry", "Biological Sciences", "Cancer", "Genetics", "Biotechnology"], "users"=>["Ai Chen", "Nicola Raule", "Anne Chomyn", "Giuseppe Attardi"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0046473.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Analysis_of_O_2_consumption_in_digitonin_permeabilized_cells_of_the_cybrid_clones_using_different_substrates_and_inhibitors_/222379", "title"=>"Analysis of O<sub>2</sub> consumption in digitonin-permeabilized cells of the cybrid clones using different substrates and inhibitors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-10-29 00:39:39"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/551977/Figure_5.tif"], "description"=>"<p>Cybrid cell lines were stained with the fluorescent membrane potential indicator dye TMRE. The fluorescence was quantified by flow cytometry. A total of 2–3 determinations were made on each cybrid cell line and the mean values are shown. The error bars indicate the standard error of the mean. Gray bars represent the average for each haplogroup. Cell lines are grouped by haplogroup. No difference between any two groups of cybrids is statistically significant.</p>", "links"=>[], "tags"=>["genetics and genomics", "public health and epidemiology", "Computational biology", "oncology", "Biochemistry"], "article_id"=>222465, "categories"=>["Biochemistry", "Biological Sciences", "Cancer", "Genetics", "Biotechnology"], "users"=>["Ai Chen", "Nicola Raule", "Anne Chomyn", "Giuseppe Attardi"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0046473.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Membrane_potential_/222465", "title"=>"Membrane potential.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-10-29 00:41:05"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/552042/Figure_6.tif"], "description"=>"<p>Cells of each cybrid clone were stained with the ROS-activated dye CM-H<sub>2</sub>DCFDA. Fluorescence data were collected on a Molecular Devices fluorescence plate reader for 1 h. A total of 2–5 rate determinations were made on each cybrid clone. Each bar represents the average fluorescence production rate for the indicated cybrid clone. The error bars indicate the standard error of the mean. The haplogroup is indicated below each group of cybrid clones. Horizontal gray lines represent the average for each haplogroup. Horizontal black bars with asterisks indicate differences between averages are statistically significant, as determined by a two-tailed unpaired t-test; *, P≤0.05; **, P<0.01.</p>", "links"=>[], "tags"=>["genetics and genomics", "public health and epidemiology", "Computational biology", "oncology", "Biochemistry"], "article_id"=>222531, "categories"=>["Biochemistry", "Biological Sciences", "Cancer", "Genetics", "Biotechnology"], "users"=>["Ai Chen", "Nicola Raule", "Anne Chomyn", "Giuseppe Attardi"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0046473.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_ROS_generation_rate_/222531", "title"=>"ROS generation rate.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-10-29 00:42:11"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/552127/Table_4.xls"], "description"=>"<p>The table lists all the individual-specific coding region polymorphisms found in the sequences of the mtDNAs of cybrids TF3A5, E8, T8, F8, and TFA7. The first column in each doublet indicates the nucleotide position of the polymorphism, the second column indicates the gene name and the nucleotide change (in the 16S or 12S rRNA genes) or the amino acid change or syn for synonymous substitution (in the protein coding genes). Polymorphisms that cause an amino acid substitution are in boldface. New, previously unreported polymorphisms are indicated in italics. We searched two databases (<a href=\"http://www.phylotree.org\" target=\"_blank\">http://www.phylotree.org</a><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046473#pone.0046473-vanOven1\" target=\"_blank\">[2]</a>;<a href=\"http://www.mitomap.org/MITOMAP\" target=\"_blank\">http://www.mitomap.org/MITOMAP</a><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046473#pone.0046473-MITOMAP1\" target=\"_blank\">[23]</a>) and found these polymorphisms absent.</p>", "links"=>[], "tags"=>["genetics and genomics", "public health and epidemiology", "Computational biology", "oncology", "Biochemistry"], "article_id"=>222618, "categories"=>["Biochemistry", "Biological Sciences", "Cancer", "Genetics", "Biotechnology"], "users"=>["Ai Chen", "Nicola Raule", "Anne Chomyn", "Giuseppe Attardi"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0046473.t004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Individual_specific_polymorphisms_/222618", "title"=>"Individual-specific polymorphisms.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-10-29 00:43:38"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/552158/Table_1.xls"], "description"=>"<p>Fibroblast strains and their haplogroups.</p>", "links"=>[], "tags"=>["strains"], "article_id"=>222660, "categories"=>["Biochemistry", "Biological Sciences", "Cancer", "Genetics", "Biotechnology"], "users"=>["Ai Chen", "Nicola Raule", "Anne Chomyn", "Giuseppe Attardi"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0046473.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Fibroblast_strains_and_their_haplogroups_/222660", "title"=>"Fibroblast strains and their haplogroups.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-10-29 00:44:20"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/552198/Table_2.xls"], "description"=>"<p>The table lists all the Control Region polymorphisms found in the sequences of the mtDNAs of cybrids TF3A5, E8, T8, F8, and TFA7. The haplogroup and subhaplogroup with which the polymorphism is associated is indicated. Most of these Control Region polymorphisms are haplogroup-specific.</p>", "links"=>[], "tags"=>["polymorphisms", "cybrid"], "article_id"=>222694, "categories"=>["Biochemistry", "Biological Sciences", "Cancer", "Genetics", "Biotechnology"], "users"=>["Ai Chen", "Nicola Raule", "Anne Chomyn", "Giuseppe Attardi"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0046473.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Control_Region_Polymorphisms_in_Cybrid_Cell_Lines_/222694", "title"=>"Control Region Polymorphisms in Cybrid Cell Lines.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-10-29 00:44:54"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/552240/Table_3.xls"], "description"=>"<p>The table lists all the haplogroup- and subhaplogroup-specifying coding region polymorphisms found in the sequences of the mtDNAs of cybrids TF3A5, E8, T8, F8, and TFA7. The first column in each triplet indicates the nucleotide position of the polymorphism, the second column indicates the gene name and the nucleotide change (in the 16S or 12S rRNA genes) or the amino acid change or syn for synonymous substitution (in the protein coding genes), and the third column indicates the haplogroup or subhaplogroup with which each particular polymorphism is associated. Polymorphisms that cause an amino acid substitution are in boldface.</p>", "links"=>[], "tags"=>["genetics and genomics", "public health and epidemiology", "Computational biology", "oncology", "Biochemistry"], "article_id"=>222730, "categories"=>["Biochemistry", "Biological Sciences", "Cancer", "Genetics", "Biotechnology"], "users"=>["Ai Chen", "Nicola Raule", "Anne Chomyn", "Giuseppe Attardi"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0046473.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Coding_Region_Polymorphisms_Haplogroup_specific_/222730", "title"=>"Coding Region Polymorphisms, Haplogroup-specific.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-10-29 00:45:30"}

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Relative Metric

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Net::HTTPTooManyRequests

Source
Scopus
Time
2019-08-15 21:09:59 UTC
Target URL
https://api.elsevier.com/content/search/index:SCOPUS?query=DOI(10.1371%2Fjournal.pone.0046473)
Trace

/app/models/concerns/networkable.rb:21:in `get_result'
/app/models/source.rb:165:in `get_data'
/app/models/retrieval_status.rb:47:in `perform_get_data'
/app/jobs/source_job.rb:52:in `block (2 levels) in perform'
/app/jobs/source_job.rb:51:in `block in perform'
/app/jobs/source_job.rb:35:in `each'
/app/jobs/source_job.rb:35:in `perform'