TGF-β1 stimulates mitochondrial oxidative phosphorylation and generation of reactive oxygen species in cultured mouse podocytes, mediated in part by the mTOR pathway
Identifieur interne : 000184 ( Main/Curation ); précédent : 000183; suivant : 000185TGF-β1 stimulates mitochondrial oxidative phosphorylation and generation of reactive oxygen species in cultured mouse podocytes, mediated in part by the mTOR pathway
Auteurs : Yoshifusa Abe [Japon, États-Unis] ; Toru Sakairi [Japon] ; Craig Beeson [États-Unis] ; Jeffrey B. Kopp [États-Unis]Source :
- American journal of physiology. Renal physiology [ 1931-857X ] ; 2013.
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- Pascal (Inist)
- Wicri :
- topic : Acidification.
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Abstract
Transforming growth factor (TGF)-β has been associated with podocyte injury; we have examined its effect on podocyte bioenergetics. We studied transformed mouse podocytes, exposed to TGF-β1, using a label-free assay system, Seahorse XF24, which measures oxygen consumption rates (OCR) and extracellular acidification rates (ECAR). Both basal OCR and ATP generation-coupled OCR were significantly higher in podocytes exposed to 0.3-10 ng/ml of TGF-β1 for 24, 48, and 72 h. TGF-β1 (3 ng/ml) increased oxidative capacity 75%, and 96% relative to control after 48 and 72 h, respectively. ATP content was increased 19% and 30% relative to control after a 48- and 72-h exposure, respectively. Under conditions of maximal mitochondrial function, TGF-β1 increased palmitate-driven OCR by 49%. Thus, TGF-β1 increases mitochondrial oxygen consumption and ATP generation in the presence of diverse energy substrates. TGF-β1 did not increase cell number or mitochondrial DNA copy number but did increase mitochondrial membrane potential (MMP), which could explain the OCR increase. Reactive oxygen species (ROS) increased by 32% after TGF-β1 exposure for 48 h. TGF-β activated the mammalian target of rapamycin (mTOR) pathway, and rapamycin reduced the TGF-β1-stimulated increases in OCR, ECAR, ATP generation, cellular metabolic activity, and protein generation. Our data suggest that TGF-β1, acting, in part, via mTOR, increases mitochondrial MMP and OCR, resulting in increased ROS generation and that this may contribute to podocyte injury.
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Kopp</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health</s1><s2>Bethesda, Maryland</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">15-0012900</idno><date when="2013">2013</date><idno type="stanalyst">PASCAL 15-0012900 INIST</idno><idno type="RBID">Pascal:15-0012900</idno><idno type="wicri:Area/PascalFrancis/Corpus">000001</idno><idno type="wicri:Area/PascalFrancis/Curation">000764</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000027</idno><idno type="wicri:doubleKey">1931-857X:2013:Abe Y:tgf:stimulates:mitochondrial</idno><idno type="wicri:Area/Main/Merge">000187</idno><idno type="wicri:Area/Main/Curation">000184</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">TGF-β1 stimulates mitochondrial oxidative phosphorylation and generation of reactive oxygen species in cultured mouse podocytes, mediated in part by the mTOR pathway</title><author><name sortKey="Abe, Yoshifusa" sort="Abe, Yoshifusa" uniqKey="Abe Y" first="Yoshifusa" last="Abe">Yoshifusa Abe</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Pediatrics, Showa University School of Medicine</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>1 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health</s1><s2>Bethesda, Maryland</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Sakairi, Toru" sort="Sakairi, Toru" uniqKey="Sakairi T" first="Toru" last="Sakairi">Toru Sakairi</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine</s1><s2>Maebashi, Gunma</s2><s3>JPN</s3><sZ>2 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Maebashi, Gunma</wicri:noRegion></affiliation></author><author><name sortKey="Beeson, Craig" sort="Beeson, Craig" uniqKey="Beeson C" first="Craig" last="Beeson">Craig Beeson</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Pharmaceutical and Biomedical Sciences, Medical University of South Carolina</s1><s2>Charleston, South Carolina</s2><s3>USA</s3><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Sud</region></placeName></affiliation></author><author><name sortKey="Kopp, Jeffrey B" sort="Kopp, Jeffrey B" uniqKey="Kopp J" first="Jeffrey B." last="Kopp">Jeffrey B. Kopp</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health</s1><s2>Bethesda, Maryland</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author></analytic><series><title level="j" type="main">American journal of physiology. Renal physiology</title><idno type="ISSN">1931-857X</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">American journal of physiology. Renal physiology</title><idno type="ISSN">1931-857X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acidification</term><term>Extracellular</term><term>Mitochondria</term><term>Mouse</term><term>Oxidative phosphorylation</term><term>Oxygen consumption</term><term>Reactive oxygen species</term><term>Rhythm</term><term>Transforming growth factor β1</term><term>Urinary system</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Facteur croissance transformant β1</term><term>Mitochondrie</term><term>Phosphorylation oxydative</term><term>Espèces réactives de l'oxygène</term><term>Souris</term><term>Consommation oxygène</term><term>Rythme</term><term>Extracellulaire</term><term>Acidification</term><term>Appareil urinaire</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Acidification</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Transforming growth factor (TGF)-β has been associated with podocyte injury; we have examined its effect on podocyte bioenergetics. We studied transformed mouse podocytes, exposed to TGF-β1, using a label-free assay system, Seahorse XF24, which measures oxygen consumption rates (OCR) and extracellular acidification rates (ECAR). Both basal OCR and ATP generation-coupled OCR were significantly higher in podocytes exposed to 0.3-10 ng/ml of TGF-β1 for 24, 48, and 72 h. TGF-β1 (3 ng/ml) increased oxidative capacity 75%, and 96% relative to control after 48 and 72 h, respectively. ATP content was increased 19% and 30% relative to control after a 48- and 72-h exposure, respectively. Under conditions of maximal mitochondrial function, TGF-β1 increased palmitate-driven OCR by 49%. Thus, TGF-β1 increases mitochondrial oxygen consumption and ATP generation in the presence of diverse energy substrates. TGF-β1 did not increase cell number or mitochondrial DNA copy number but did increase mitochondrial membrane potential (MMP), which could explain the OCR increase. Reactive oxygen species (ROS) increased by 32% after TGF-β1 exposure for 48 h. TGF-β activated the mammalian target of rapamycin (mTOR) pathway, and rapamycin reduced the TGF-β1-stimulated increases in OCR, ECAR, ATP generation, cellular metabolic activity, and protein generation. Our data suggest that TGF-β1, acting, in part, via mTOR, increases mitochondrial MMP and OCR, resulting in increased ROS generation and that this may contribute to podocyte injury.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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