C. elegans Aging Is Modulated by Hydrogen Sulfide and the sulfhydrylase/cysteine Synthase cysl-2
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{"title"=>"C. elegans aging is modulated by hydrogen sulfide and the sulfhydrylase/cysteine synthase cysl-2", "type"=>"journal", "authors"=>[{"first_name"=>"Bedoor", "last_name"=>"Qabazard", "scopus_author_id"=>"56005580800"}, {"first_name"=>"Samanza", "last_name"=>"Ahmed", "scopus_author_id"=>"56005190200"}, {"first_name"=>"Ng", "last_name"=>"Li", "scopus_author_id"=>"56004851100"}, {"first_name"=>"Volker M.", "last_name"=>"Arlt", "scopus_author_id"=>"35563918200"}, {"first_name"=>"Philip K.", "last_name"=>"Moore", "scopus_author_id"=>"7403685599"}, {"first_name"=>"Stephen R.", "last_name"=>"Stürzenbaum", "scopus_author_id"=>"6603711846"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pmid"=>"24260346", "scopus"=>"2-s2.0-84892537477", "doi"=>"10.1371/journal.pone.0080135", "sgr"=>"84892537477", "pui"=>"372141694"}, "id"=>"c18a2de6-ddf0-31f4-a223-b2b6e19e6c12", "abstract"=>"Exogenous hydrogen sulfide (H2S) administration and endogenous H2S metabolism were explored in the nematode C. elegans. Chronic treatment with a slow-releasing H2S donor, GYY4137, extended median survival by 17-23% and increased tolerance towards oxidative and endoplasmic reticulum (ER) stress. Also, cysl-2, a sulfhydrylase/cysteine synthase in C. elegans, was transcriptionally upregulated by GYY4137 treatment and the deletion of cysl-2 resulted in a significant reduction in lifespan which was partially recovered by the supplementation of GYY4137. Likewise, a mammalian cell culture system, GYY4137 was able to protect bovine aortic endothelial cells (BAECs) from oxidative stress and (H2O2)-induced cell death. Taken together, this provides further support that H2S exerts a protective function which is consistent with the longevity dividend theory. Overall, this study underlines the therapeutic potential of a slow-releasing H2S donor as regulators of the aging and cellular stress pathways.", "link"=>"http://www.mendeley.com/research/c-elegans-aging-modulated-hydrogen-sulfide-sulfhydrylasecysteine-synthase-cysl2", "reader_count"=>31, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>4, "Researcher"=>6, "Student > Ph. D. Student"=>7, "Student > Master"=>6, "Other"=>2, "Student > Bachelor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>4, "Researcher"=>6, "Student > Ph. D. Student"=>7, "Student > Master"=>6, "Other"=>2, "Student > Bachelor"=>3}, "reader_count_by_subject_area"=>{"Engineering"=>4, "Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>12, "Medicine and Dentistry"=>1, "Neuroscience"=>1, "Physics and Astronomy"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>4}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Unspecified"=>{"Unspecified"=>4}}, "group_count"=>3}

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Figshare

  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/1273139/Figure_1.tif"], "description"=>"<p>(A)Intracellular levels of ROS were obtained from age-synchronized worms assayed at L4 stage following treatment with vehicle (control) or GYY4137 (100 µM) for 48 hours in liquid medium. Each bar represents data from 3 independent experiments with at least 2000 worms in each treatment group and normalized by the calculated protein content (* and ***, statistically significant c.f. control; p < 0.05 and p < 0.001, respectively). GYY4137 treatment improved (B) survival and (C-D) growth (body area and length) in wild type worms. Nematodes were exposed to the drug from L1 larval stage until death (day of death refers to the age (days) post L1); survival curves were plotted by the Kaplan-Meier method and median survival values were compared by log-rank (Mantel-Cox) test with 95% significance using GraphPad Prism v5 software. GYY4137 treatment improves the resistance of wild type nematodes to (E) oxidative, (F) ER and (H) thermal stressors, but notably not to (G) cadmium-induced stress. </p>", "links"=>[], "tags"=>["slow-releasing", "gyy4137", "mediates", "aging"], "article_id"=>844981, "categories"=>["Biological Sciences"], "users"=>["Bedoor Qabazard", "Samanza Ahmed", "Ling Li", "Volker M. Arlt", "Philip K. Moore", "Stephen R. Stürzenbaum"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0080135.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_The_slow_releasing_H_2_S_donor_GYY4137_mediates_an_aging_and_stress_response_in_C_elegans_/844981", "title"=>"The slow-releasing H<sub>2</sub>S donor GYY4137 mediates an aging and stress response in <i>C. elegans</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-08 03:00:01"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/1273140/Figure_2.tif"], "description"=>"<p>Genes involved in aging- and stress-related pathways were selected to evaluate, by qPCR, expression changes associated with GYY4137 treatment (A) in wild type <i>C. elegans</i> in the absence (-) or presence (+) of GYY4137 (100 µM) and (B) in <i>cysl-2</i> mutants compared to N2 wild type (in the absence of GYY4137).</p>", "links"=>[], "tags"=>["transcriptional", "wildtype", "exposed", "gyy4137"], "article_id"=>844982, "categories"=>["Biological Sciences"], "users"=>["Bedoor Qabazard", "Samanza Ahmed", "Ling Li", "Volker M. Arlt", "Philip K. Moore", "Stephen R. Stürzenbaum"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0080135.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_The_transcriptional_response_of_wildtype_exposed_to_GYY4137_and_in_cycl_2_mutants_/844982", "title"=>"The transcriptional response of wildtype exposed to GYY4137 and in <i>cycl-2</i> mutants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-08 03:00:01"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/1273141/Figure_3.tif"], "description"=>"<p>(A) The <i>cysl-2</i> mutant has a reduced rate of enzymatic H<sub>2</sub>S synthesis from the added substrates L-cysteine. (B) The <i>cysl-2</i> mutant is marked by a decline in reproductive output compared to wild type worms. (C) Body area and (D) length are significantly lower in <i>cysl-2</i> compared to age-matched wild type worms, and GYY4137 treatment (100 µM) effectively rescued this phenotype. (E) Lifespan is reduced in <i>cysl-2</i> compared to wild type (median survival of 11 days vs. 12 days, respectively) and the addition of GYY4137 (100 µM) reverses this effect and increases the median survival of <i>cysl-2</i>. </p>", "links"=>[], "tags"=>["mutant"], "article_id"=>844983, "categories"=>["Biological Sciences"], "users"=>["Bedoor Qabazard", "Samanza Ahmed", "Ling Li", "Volker M. Arlt", "Philip K. Moore", "Stephen R. Stürzenbaum"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0080135.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_The_cysl_2_mutant_phenotype_/844983", "title"=>"The <i>cysl-2</i> mutant phenotype.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-08 03:00:01"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/1273142/Figure_4.tif"], "description"=>"<p>(A) Cell viability was determined with the CTB assay. Cell viability testing after 24 hours incubation of BAEC cultures with a range of concentrations of the slow-releasing H<sub>2</sub>S donor GYY4137 or the oxidative stress inducer H<sub>2</sub>O<sub>2</sub>. (B) Representative images of BAEC treated cultures in the presence or absence of H<sub>2</sub>O<sub>2</sub> (100 µM) and GYY4137 (100 µM). (C) Effect of GYY4137 on cell death induced by H<sub>2</sub>O<sub>2</sub> (100 µM). BAEC were exposed to H<sub>2</sub>O<sub>2</sub> in the presence or absence of GYY4137 (100 µM) for 24 hours and cell viability was determined by means of the CTB assay. Data are expressed as percentage of untreated control from 6 repeats. </p>", "links"=>[], "tags"=>["protects", "baecs", "oxidative"], "article_id"=>844984, "categories"=>["Biological Sciences"], "users"=>["Bedoor Qabazard", "Samanza Ahmed", "Ling Li", "Volker M. Arlt", "Philip K. Moore", "Stephen R. Stürzenbaum"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0080135.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_GYY4137_protects_BAECs_from_oxidative_stress_H_2_O_2_induced_cell_death_/844984", "title"=>"GYY4137 protects BAECs from oxidative stress (H<sub>2</sub>O<sub>2</sub>)-induced cell death.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-08 03:00:01"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/1273143/Figure_S1.tif", "https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/1273144/Table_S1.docx", "https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/1273145/Table_S2.docx"], "description"=>"<div><p>Exogenous hydrogen sulfide (H<sub>2</sub>S) administration and endogenous H<sub>2</sub>S metabolism were explored in the nematode <i>C. elegans</i>. Chronic treatment with a slow-releasing H<sub>2</sub>S donor, GYY4137, extended median survival by 17-23% and increased tolerance towards oxidative and endoplasmic reticulum (ER) stress. Also, <i>cysl-2</i>, a sulfhydrylase/cysteine synthase in <i>C. elegans</i>, was transcriptionally upregulated by GYY4137 treatment and the deletion of <i>cysl-2</i> resulted in a significant reduction in lifespan which was partially recovered by the supplementation of GYY4137. Likewise, a mammalian cell culture system, GYY4137 was able to protect bovine aortic endothelial cells (BAECs) from oxidative stress and (H<sub>2</sub>O<sub>2</sub>)-induced cell death. Taken together, this provides further support that H<sub>2</sub>S exerts a protective function which is consistent with the longevity dividend theory. Overall, this study underlines the therapeutic potential of a slow-releasing H<sub>2</sub>S donor as regulators of the aging and cellular stress pathways. </p> </div>", "links"=>[], "tags"=>["aging", "modulated", "hydrogen", "sulfide", "synthase"], "article_id"=>844985, "categories"=>["Biological Sciences"], "users"=>["Bedoor Qabazard", "Samanza Ahmed", "Ling Li", "Volker M. Arlt", "Philip K. Moore", "Stephen R. Stürzenbaum"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0080135"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_C_elegans_Aging_Is_Modulated_by_Hydrogen_Sulfide_and_the_sulfhydrylase_cysteine_Synthase_cysl_2_/844985", "title"=>"<i>C. elegans</i> Aging Is Modulated by Hydrogen Sulfide and the sulfhydrylase/cysteine Synthase <i>cysl-2</i>", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-11-08 03:00:01"}

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