The Mitochondria-Targeted Antioxidants and Remote Kidney Preconditioning Ameliorate Brain Damage through Kidney-to-Brain Cross-Talk
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{"title"=>"The Mitochondria-Targeted Antioxidants and Remote Kidney Preconditioning Ameliorate Brain Damage through Kidney-to-Brain Cross-Talk", "type"=>"journal", "authors"=>[{"first_name"=>"Denis N.", "last_name"=>"Silachev", "scopus_author_id"=>"16204167400"}, {"first_name"=>"Nikolay K.", "last_name"=>"Isaev", "scopus_author_id"=>"35463878500"}, {"first_name"=>"Irina B.", "last_name"=>"Pevzner", "scopus_author_id"=>"7003895047"}, {"first_name"=>"Ljubava D.", "last_name"=>"Zorova", "scopus_author_id"=>"6506901552"}, {"first_name"=>"Elena V.", "last_name"=>"Stelmashook", "scopus_author_id"=>"55885114200"}, {"first_name"=>"Svetlana V.", "last_name"=>"Novikova", "scopus_author_id"=>"36470902500"}, {"first_name"=>"Egor Y.", "last_name"=>"Plotnikov", "scopus_author_id"=>"8837168500"}, {"first_name"=>"Vladimir P.", "last_name"=>"Skulachev", "scopus_author_id"=>"35468160400"}, {"first_name"=>"Dmitry B.", "last_name"=>"Zorov", "scopus_author_id"=>"7004151848"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23272118", "doi"=>"10.1371/journal.pone.0051553", "sgr"=>"84871334541", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-84871334541", "issn"=>"19326203", "pui"=>"366296337"}, "id"=>"0172118f-7a99-374a-be49-7417f4db18e0", "abstract"=>"BACKGROUND: Many ischemia-induced neurological pathologies including stroke are associated with high oxidative stress. Mitochondria-targeted antioxidants could rescue the ischemic organ by providing specific delivery of antioxidant molecules to the mitochondrion, which potentially suffers from oxidative stress more than non-mitochondrial cellular compartments. Besides direct antioxidative activity, these compounds are believed to activate numerous protective pathways. Endogenous anti-ischemic defense may involve the very powerful neuroprotective agent erythropoietin, which is mainly produced by the kidney in a redox-dependent manner, indicating an important role of the kidney in regulation of brain ischemic damage. The goal of this study is to track the relations between the kidney and the brain in terms of the amplification of defense mechanisms during SkQR1 treatment and remote renal preconditioning and provide evidence that the kidney can generate signals inducing a tolerance to oxidative stress-associated brain pathologies.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: We used the cationic plastoquinone derivative, SkQR1, as a mitochondria-targeted antioxidant to alleviate the deleterious consequences of stroke. A single injection of SkQR1 before cerebral ischemia in a dose-dependent manner reduces infarction and improves functional recovery. Concomitantly, an increase in the levels of erythropoietin in urine and phosphorylated glycogen synthase kinase-3β (GSK-3β) in the brain was detected 24 h after SkQR1 injection. However, protective effects of SkQR1 were not observed in rats with bilateral nephrectomy and in those treated with the nephrotoxic antibiotic gentamicin, indicating the protective role of humoral factor(s) which are released from functional kidneys. Renal preconditioning also induced brain protection in rats accompanied by an increased erythropoietin level in urine and kidney tissue and P-GSK-3β in brain. Co-cultivation of SkQR1-treated kidney cells with cortical neurons resulted in enchanced phosphorylation of GSK-3β in neuronal cells.\\n\\nCONCLUSION: The results indicate that renal preconditioning and SkQR1-induced brain protection may be mediated through the release of EPO from the kidney.", "link"=>"http://www.mendeley.com/research/mitochondriatargeted-antioxidants-remote-kidney-preconditioning-ameliorate-brain-damage-through-kidn", "reader_count"=>23, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>10, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>2, "Other"=>2, "Student > Master"=>1, "Student > Bachelor"=>1, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>10, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>2, "Other"=>2, "Student > Master"=>1, "Student > Bachelor"=>1, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>9, "Medicine and Dentistry"=>6, "Neuroscience"=>1, "Design"=>1, "Arts and Humanities"=>1, "Chemistry"=>1, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"Germany"=>1, "Russia"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/524440"], "description"=>"<p>Rats in SkQR1-pretreated groups (A, B, C) were given i/p SkQR1 (0.5, 1, 2 µmol/kg) or (D, E, F) subjected to remote renal preconditioning (RRPC) 24 h prior to ischemia. (A, D) Representative photomicrographs from coronal brain sections (2 mm thick, from rostral (top) towards caudal (bottom)) stained with TTC 24 h after reperfusion. Lack of red staining indicates infarction. (B, E) Infarct volume and (C, F) brain edema (swelling) were measured in the TTC-stained brain sections. * Denotes significantly different from the MCAO+VEHICLE or MCAO groups (p<0.05) (One-way ANOVA, followed by Tukey’s post hoc analysis or <i>t</i> tests for independent samples).</p>", "links"=>[], "tags"=>["skqr1", "rrpc", "mcao", "protects", "ischemic", "injured"], "article_id"=>194913, "categories"=>["Physiology", "Biochemistry", "Neuroscience", "Cell Biology"], "users"=>["Denis N. Silachev", "Nikolay K. Isaev", "Irina B. Pevzner", "Ljubava D. Zorova", "Elena V. Stelmashook", "Svetlana V. Novikova", "Egor Y. Plotnikov", "Vladimir P. Skulachev", "Dmitry B. Zorov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0051553.g001", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_treatment_with_SkQR1_and_RRPC_starting_before_the_MCAO_protects_the_ischemic_injured_brain_/194913", "title"=>"The treatment with SkQR1 and RRPC starting before the MCAO protects the ischemic injured brain.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 18:37:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/524994"], "description"=>"a<p>The neurological state scores are recorded in a blind fashion and expressed as median and interquartile ranges, the 25th to 75th percentile are shown in the parentheses. Baseline represents neurological state of intacte rats. *Denotes significant from the score at 24 h after the MCAO compared to MCAO+ VEHICLE or MCAO groups (p<0.05) (Kruskal-Wallis test with the Mann–Whitney <i>u</i>-test with Bonferroni correction post hoc or Mann–Whitney test when comparing between two groups).</p>", "links"=>[], "tags"=>["physiology", "cell biology", "neuroscience", "Biochemistry"], "article_id"=>195477, "categories"=>["Physiology", "Biochemistry", "Neuroscience", "Cell Biology"], "users"=>["Denis N. Silachev", "Nikolay K. Isaev", "Irina B. Pevzner", "Ljubava D. Zorova", "Elena V. Stelmashook", "Svetlana V. Novikova", "Egor Y. Plotnikov", "Vladimir P. Skulachev", "Dmitry B. Zorov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0051553.t001", "stats"=>{"downloads"=>8, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Neurological_state_a_/195477", "title"=>"Neurological state<sup>a</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 18:40:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/525035"], "description"=>"a<p>Hematological parameters changes after treatment with 2 µmol/kg SkQR1 for 12 h: Vehicle (n = 8) and SkQR1 (n = 8); for 24 h: Vehicle (n = 6) and SkQR1, (n = 7). RBC, red blood cells; HGB, hemoglobin; HCT, hematocrit.</p>*<p>Denotes significantly different from the vehicle group (p<0.05) (<i>t</i> tests).</p>", "links"=>[], "tags"=>["physiology", "cell biology", "neuroscience", "Biochemistry"], "article_id"=>195526, "categories"=>["Physiology", "Biochemistry", "Neuroscience", "Cell Biology"], "users"=>["Denis N. Silachev", "Nikolay K. Isaev", "Irina B. Pevzner", "Ljubava D. Zorova", "Elena V. Stelmashook", "Svetlana V. Novikova", "Egor Y. Plotnikov", "Vladimir P. Skulachev", "Dmitry B. Zorov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0051553.t002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hematological_parameters_a_/195526", "title"=>"Hematological parameters<sup>a</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 18:40:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/524566"], "description"=>"<p>(<b>A</b>) Changes in erythropoietin (EPO) level in the daily urine. 1 or 2 µmol/kg SkQR1 was injected i/p 24 h before urine collection. Rats were subjected to RRPC for 24 h and gentamicin for 6 days prior to urine collection. (<b>B</b>) Detection of phosphorylated glycogen synthase kinase-3β (P-GSK-3β) in the total brain tissue. Representative Western blots with corresponding densitometry averaged over 6 blots are shown. Band densities were normalized to the density of total GSK-3β band. 1 µmol/kg SkQR1 was injected i/p 24 h before excising the brain. (<b>C1–4</b>) Detection of P-GSK-3β in cultured cortical neurons (CNs) after co-culturing with renal tubular cells (RTC) treated with 250 nM SkQR1 for 1 h before 24 h of co-culturing (C1); control CNs (C2); co-culture of CNs and RTC (C3); co-culture of CNs with RTC primed with SkQR1 (C4). (<b>D</b>) Detection of P-GSK-3β in the cultural glial cells treated with 50 or 100 nM SkQR1 for 24 h. (<b>E</b>) Detection of EPO in the entire brain tissue. Densitometry of Western EPO spots averaged over 6 blots is shown. 1 µmol/kg SkQR1 was injected i/p 3 or 24 h before excising the brain. * Denotes significantly different from the control group (p<0.05) (One-way ANOVA, followed by Tukey’s post hoc analysis or <i>t</i> tests for independent samples).</p>", "links"=>[], "tags"=>["rrpc", "ischemic"], "article_id"=>195057, "categories"=>["Physiology", "Biochemistry", "Neuroscience", "Cell Biology"], "users"=>["Denis N. Silachev", "Nikolay K. Isaev", "Irina B. Pevzner", "Ljubava D. Zorova", "Elena V. Stelmashook", "Svetlana V. Novikova", "Egor Y. Plotnikov", "Vladimir P. Skulachev", "Dmitry B. Zorov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0051553.g002", "stats"=>{"downloads"=>1, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SkQR1_and_RRPC_provide_some_features_of_ischemic_tolerance_/195057", "title"=>"SkQR1 and RRPC provide some features of ischemic tolerance.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 18:38:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/524758"], "description"=>"<p>The effects of SkQR1 after bilateral nephrectomy on the brain infarct volume and brain swelling of rats exposed to MCAO are shown in (A, B) and (C) correspondingly. Nephrotoxic gentamicin pretreatment shows similar abrogation of beneficial effects of SkQR1 and RRPC on the brain infarct volume (D, E) and brain swelling (F) of rats exposed to MCAO. (A, D) Representative T2-weighted MR-images from coronal brain sections (0.5 mm thick, from rostral (top) towards caudal (bottom)) obtained 24 h after reperfusion. Hyperintensities regions refer to ischemic areas. The evaluation of the brain damage area and brain swelling were done by using MRI with analysis of T2-weighted images.</p>", "links"=>[], "tags"=>["nephrectomy", "gentamicin", "pretreatment", "abolish", "neuroprotective", "skqr1"], "article_id"=>195240, "categories"=>["Physiology", "Biochemistry", "Neuroscience", "Cell Biology"], "users"=>["Denis N. Silachev", "Nikolay K. Isaev", "Irina B. Pevzner", "Ljubava D. Zorova", "Elena V. Stelmashook", "Svetlana V. Novikova", "Egor Y. Plotnikov", "Vladimir P. Skulachev", "Dmitry B. Zorov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0051553.g003", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bilateral_nephrectomy_and_gentamicin_pretreatment_abolish_neuroprotective_action_of_SkQR1_and_RRPC_/195240", "title"=>"Bilateral nephrectomy and gentamicin pretreatment abolish neuroprotective action of SkQR1 and RRPC.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 18:38:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/524882"], "description"=>"<p>SkQR1 retention and distribution over kidney and brain compartments 3 and 24 hrs after i/p injection of 1 µmol/kg SkQR1. Confocal microscopy of tissues slices. As a negative control, organs from untreated animals were also analyzed. Bar, 50 µm.</p>", "links"=>[], "tags"=>["accumulates", "kidney"], "article_id"=>195374, "categories"=>["Physiology", "Biochemistry", "Neuroscience", "Cell Biology"], "users"=>["Denis N. Silachev", "Nikolay K. Isaev", "Irina B. Pevzner", "Ljubava D. Zorova", "Elena V. Stelmashook", "Svetlana V. Novikova", "Egor Y. Plotnikov", "Vladimir P. Skulachev", "Dmitry B. Zorov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0051553.g004", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SkQR1_accumulates_in_kidney_but_not_in_brain_/195374", "title"=>"SkQR1 accumulates in kidney but not in brain.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 18:39:45"}

PMC Usage Stats | Further Information

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Relative Metric

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