MitoNEET Protects HL-1 Cardiomyocytes from Oxidative Stress Mediated Apoptosis in an In Vitro Model of Hypoxia and Reoxygenation
Publication Date
May 31, 2016
Journal
PLOS ONE
Authors
Anika Habener, Arpita Chowdhury, Frank Echtermeyer, Ralf Lichtinghagen, et al
Volume
11
Issue
5
Pages
e0156054
DOI
https://dx.plos.org/10.1371/journal.pone.0156054
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0156054
Scopus
84971663790
Mendeley
http://www.mendeley.com/research/mitoneet-protects-hl1-cardiomyocytes-oxidative-stress-mediated-apoptosis-vitro-model-hypoxia-reoxyge
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Mendeley | Further Information

{"title"=>"MitoNEET protects HL-1 cardiomyocytes from oxidative stress mediated apoptosis in an in vitro model of hypoxia and reoxygenation", "type"=>"journal", "authors"=>[{"first_name"=>"Anika", "last_name"=>"Habener", "scopus_author_id"=>"57189455805"}, {"first_name"=>"Arpita", "last_name"=>"Chowdhury", "scopus_author_id"=>"56048234100"}, {"first_name"=>"Frank", "last_name"=>"Echtermeyer", "scopus_author_id"=>"6602636587"}, {"first_name"=>"Ralf", "last_name"=>"Lichtinghagen", "scopus_author_id"=>"7003928405"}, {"first_name"=>"Gregor", "last_name"=>"Theilmeier", "scopus_author_id"=>"55979408600"}, {"first_name"=>"Christine", "last_name"=>"Herzog", "scopus_author_id"=>"35553491300"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"610575907", "pmid"=>"27243905", "doi"=>"10.1371/journal.pone.0156054", "issn"=>"19326203", "scopus"=>"2-s2.0-84971663790", "sgr"=>"84971663790", "isbn"=>"1932-6203"}, "id"=>"fe7b8ad1-eac7-3e93-b8b4-5e6e037e5d01", "abstract"=>"The iron-sulfur cluster containing protein mitoNEET is known to modulate the oxidative capacity of cardiac mitochondria but its function during myocardial reperfusion injury after transient ischemia is unknown. The purpose of this study was to analyze the impact of mito-NEET on oxidative stress induced cell death and its relation to the glutathione-redox system in cardiomyocytes in an in vitro model of hypoxia and reoxygenation (H/R). Our results show that siRNA knockdown (KD) of mitoNEET caused an 1.9-fold increase in H/R induced apoptosis compared to H/R control while overexpression of mitoNEET caused a 53% decrease in apoptosis. Necrosis was not affected. Apoptosis of both, mitoNEET-KD and control cells was diminished to comparable levels by using the antioxidants Tiron and gluta-thione compound glutathione reduced ethyl ester (GSH-MEE), indicating that mitoNEET-dependent apoptosis is mediated by oxidative stress. The interplay between mitoNEET and glutathione redox system was assessed by treating cardiomyocytes with 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanylthio-carbonylamino) phenylthiocarbamoylsulfanyl] propionic acid (2-AAPA), known to effectively inhibit glutathione reductase (GSR) and to decrease the GSH/GSSG ratio. Surprisingly, inhibition of GSR-activity to 20% by 2-AAPA decreased apoptosis of control and mitoNEET-KD cells to 23% and 25% respectively, while at the same time mitoNEET-protein was increased 4-fold. This effect on mitoNEET-protein was not accessible by mitoNEET-KD but was reversed by GSH-MEE. In conclusion we show that mitoNEET protects cardiomyocytes from oxidative stress-induced apoptosis dur-ing H/R. Inhibition of GSH-recycling, GSR-activity by 2-AAPA increased mitoNEET-protein, accompanied by reduced apoptosis. Addition of GSH reversed these effects suggesting that mitoNEET can in part compensate for imbalances in the antioxidative glutathione-PLOS ONE | Funding: This study was supported by grants from the Deutsche Forschungsgemeinschaft (DFG, grant numbers: Th667/6-1 and 7-1; KFO136, TP12 (GT and CH)). The funders had no role in study design, data collection, analysis and interpretation, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Abbreviations: 2-AAPA, 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanylthio-system and therefore could serve as a potential therapeutic approach for the oxidatively stressed myocardium.", "link"=>"http://www.mendeley.com/research/mitoneet-protects-hl1-cardiomyocytes-oxidative-stress-mediated-apoptosis-vitro-model-hypoxia-reoxyge", "reader_count"=>10, "reader_count_by_academic_status"=>{"Student > Doctoral Student"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>3, "Student > Master"=>2, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Student > Doctoral Student"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>3, "Student > Master"=>2, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Medicine and Dentistry"=>2, "Agricultural and Biological Sciences"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>0}

Scopus | Further Information

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