Genetic Activation of Nrf2 Protects against Fasting-Induced Oxidative Stress in Livers of Mice
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{"title"=>"Genetic Activation of Nrf2 Protects against Fasting-Induced Oxidative Stress in Livers of Mice", "type"=>"journal", "authors"=>[{"first_name"=>"Yu Kun Jennifer", "last_name"=>"Zhang", "scopus_author_id"=>"16237798400"}, {"first_name"=>"Kai Connie", "last_name"=>"Wu", "scopus_author_id"=>"53867391000"}, {"first_name"=>"Curtis D.", "last_name"=>"Klaassen", "scopus_author_id"=>"7201356302"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84875061355", "doi"=>"10.1371/journal.pone.0059122", "sgr"=>"84875061355", "pmid"=>"23527105", "issn"=>"19326203", "pui"=>"368539622"}, "id"=>"fb065878-3dd4-37d3-ac8c-8b4d3d42ee2a", "abstract"=>"Acute fasting causes elevated oxidative stress. The current study investigated the effects of the nuclear factor erythoid 2-related factor 2 (Nrf2), the sensor of oxidative stress in cells, on energy homeostasis and liver pathophysiology during fasting. Feed was removed from mice possessing none (Nrf2-null), normal (wild-type, WT), enhanced (Keap1-knockdown, K1-KD), and maximum (hepatocyte-specific Keap1-knockout, K1-HKO) Nrf2 activity in liver for 24 h. Body weight, blood glucose, and blood lipid profiles were similar among mice with graded Nrf2 activity under either fed or fasted conditions. Fasting reduced liver size in mice expressing Nrf2, but not in Nrf2-null mice. Nrf2-null mice accumulated more non-esterified free fatty acids and triglycerides in liver after fasting than the other genotypes of mice. Fatty acids are mainly catabolized in mitochondria, and Nrf2-null mice had lower mitochondrial content in liver under control feeding conditions, which was further reduced by fasting. In contrast, mitochondrial contents in mice with enhanced Nrf2 activity were not affected by fasting. Oxidative stress, determined by staining of free radicals and quantification of malondialdehyde equivalents, was highest in Nrf2-null and lowest in K1-HKO mice after fasting. The exacerbated oxidative stress in livers of Nrf2-null mice is predicted to lead to damages to mitochondria, and therefore diminished oxidation and increased accumulation of lipids in livers of Nrf2-null mice. In summary, the Nrf2-regulated signaling pathway is critical in protecting mitochondria from oxidative stress during feed deprivation, which ensures efficient utilization of fatty acids in livers of mice.", "link"=>"http://www.mendeley.com/research/genetic-activation-nrf2-protects-against-fastinginduced-oxidative-stress-livers-mice", "reader_count"=>36, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Librarian"=>1, "Student > Doctoral Student"=>5, "Researcher"=>5, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>1, "Student > Master"=>10, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Librarian"=>1, "Student > Doctoral Student"=>5, "Researcher"=>5, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>1, "Student > Master"=>10, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>22, "Medicine and Dentistry"=>5, "Chemistry"=>2, "Computer Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Chemistry"=>{"Chemistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>22}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Spain"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/990431"], "description"=>"<p>(A) Messenger RNA expression of Nrf2 and Nrf2-target genes after a 24-h fasting. (B) Hepatic expression of Nrf2 and Nqo1 after either a 36-h fasting or a 24-h fasting followed by a 12-h refeeding. Data are presented as mean ± S.E. (n = 3−5). Two-way ANOVA was performed with genotype and treatment as main factors. Significant main effects and interactions were followed by Student-Newman-Keuls comparisons to assess the differences between groups. Asterisks (*) represent statistical differences (<i>p</i><0.05) compared with WT mice on the same treatment. Pounds (#) represent statistical differences (<i>p</i><0.05) between fasted (or refed) and control mice of the same genotype.</p>", "links"=>[], "tags"=>["rna", "nrf2", "nrf2-regulated", "genes"], "article_id"=>654569, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology"], "users"=>["Yu-Kun Jennifer Zhang", "Kai Connie Wu", "Curtis D. Klaassen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0059122.g005", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Messenger_RNA_expression_of_Nrf2_and_Nrf2_regulated_genes_in_mouse_livers_/654569", "title"=>"Messenger RNA expression of Nrf2 and Nrf2-regulated genes in mouse livers.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-19 09:33:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/990429"], "description"=>"<p>(A) Messenger RNA of genes encoding key enzymes for gluconeogenesis. (B) Messenger RNA expression of PPARα and genes involved in fatty acid catabolism. Data are presented as mean ± S.E. (n = 5). Two-way ANOVA was performed with genotype and treatment as main factors. Significant main effects and interactions were followed by Student-Newman-Keuls comparisons to assess the differences between groups. Asterisks (*) represent statistical differences (<i>p</i><0.05) compared with WT mice on the same treatment. Pounds (#) represent statistical differences (<i>p</i><0.05) between fasted and control mice of the same genotype.</p>", "links"=>[], "tags"=>["genes", "glucose", "lipid"], "article_id"=>654567, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology"], "users"=>["Yu-Kun Jennifer Zhang", "Kai Connie Wu", "Curtis D. Klaassen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0059122.g003", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hepatic_expression_of_genes_involved_in_glucose_and_lipid_metabolism_/654567", "title"=>"Hepatic expression of genes involved in glucose and lipid metabolism.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-19 09:32:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/990430"], "description"=>"<p>(A) Detection of superoxide in liver. Frozen liver tissue was cut into 6 µM sections and stained with dihydrothidium (DHE). (B) Contents of lipid peroxidation products (represented by malonaldehyde equivalent) and the reductive GSH in livers of mice possessing different Nrf2 activity. Data are presented as mean ± S.E. (n = 5). Two-way ANOVA was performed with genotype and treatment as main factors. Significant main effects and interactions were followed by Student-Newman-Keuls comparisons to assess the differences between groups. Asterisks (*) represent statistical differences (<i>p</i><0.05) compared with WT mice on the same treatment. Pounds (#) represent statistical differences (<i>p</i><0.05) between fasted and control mice of the same genotype.</p>", "links"=>[], "tags"=>["glutathione", "contents"], "article_id"=>654568, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology"], "users"=>["Yu-Kun Jennifer Zhang", "Kai Connie Wu", "Curtis D. Klaassen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0059122.g004", "stats"=>{"downloads"=>1, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Oxidative_stress_and_glutathione_GSH_contents_in_mouse_livers_/654568", "title"=>"Oxidative stress and glutathione (GSH) contents in mouse livers.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-19 09:33:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/990428"], "description"=>"<p>(A) Plasma concentrations of glucose, non-esterified fatty acids (NEFAs), and triglycerides. (B) Liver contents of glycogen, NEFAs, and triglycerides. Data are presented as mean ± S.E. (n = 5). Two-way ANOVA was performed with genotype and treatment as main factors. Significant main effects and interactions were followed by Student-Newman-Keuls comparisons to assess the differences between groups. Asterisks (*) represent statistical differences (<i>p</i><0.05) compared with WT mice on the same treatment. Pounds (#) represent statistical differences (<i>p</i><0.05) between fasted and control mice of the same genotype.</p>", "links"=>[], "tags"=>["lipid", "profiles"], "article_id"=>654566, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology"], "users"=>["Yu-Kun Jennifer Zhang", "Kai Connie Wu", "Curtis D. Klaassen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0059122.g002", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Glucose_and_lipid_profiles_in_blood_and_liver_/654566", "title"=>"Glucose and lipid profiles in blood and liver.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-19 09:31:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/990433"], "description"=>"<p>(A) Messenger RNA expression of transcription factors regulating mitochondria biogenesis in liver. (B) Relative mitochondrial content in livers of control and fasted mice. Data are presented as mean ± S.E. (n = 5). Two-way ANOVA was performed with genotype and treatment as main factors. Significant main effects and interactions were followed by Student-Newman-Keuls comparisons to assess the differences between groups. Asterisks (*) represent statistical differences (<i>p</i><0.05) compared with WT mice on the same treatment. Pounds (#) represent statistical differences (<i>p</i><0.05) between fasted and control mice of the same genotype.</p>", "links"=>[], "tags"=>["mitochondrial", "livers", "mice", "24-h"], "article_id"=>654571, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology"], "users"=>["Yu-Kun Jennifer Zhang", "Kai Connie Wu", "Curtis D. Klaassen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0059122.g006", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PGC_1_945_expression_and_mitochondrial_content_in_livers_of_mice_after_24_h_fasting_/654571", "title"=>"PGC-1α expression and mitochondrial content in livers of mice after 24-h fasting.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-19 09:34:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/990427"], "description"=>"<p>(A) Body weight. (B) Liver-body weight ratio. Nrf2-null, wild-type (WT), Keap1-knockdown (K1-KD), and Keap1-1 hepatocytes-specific knockout (K1-HKO) mice were either fed laboratory chow or fasted for 24 h. Data are presented as mean ± S.E. (n = 5). Two-way ANOVA was performed with genotype and treatment as main factors. Significant main effects and interactions were followed by Student-Newman-Keuls comparisons to assess the differences between groups. Asterisks (*) represent statistical differences (<i>p</i><0.05) compared with WT mice on the same treatment. Pounds (#) represent statistical differences (<i>p</i><0.05) caused by fasting in (A); and between fasted and control mice of the same genotype in (B).</p>", "links"=>[], "tags"=>["molecular biology", "cell biology", "Biochemistry"], "article_id"=>654565, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology"], "users"=>["Yu-Kun Jennifer Zhang", "Kai Connie Wu", "Curtis D. Klaassen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0059122.g001", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Body_weight_and_liver_weight_/654565", "title"=>"Body weight and liver weight.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-19 09:31:41"}

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Relative Metric

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