Serveur d'exploration sur la glutarédoxine

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Glutaredoxin regulates apoptosis in cardiomyocytes via NFkappaB targets Bcl-2 and Bcl-xL: implications for cardiac aging.

Identifieur interne : 000A26 ( Main/Exploration ); précédent : 000A25; suivant : 000A27

Glutaredoxin regulates apoptosis in cardiomyocytes via NFkappaB targets Bcl-2 and Bcl-xL: implications for cardiac aging.

Auteurs : Molly M. Gallogly [États-Unis] ; Melissa D. Shelton ; Suparna Qanungo ; Harish V. Pai ; David W. Starke ; Charles L. Hoppel ; Edward J. Lesnefsky ; John J. Mieyal

Source :

RBID : pubmed:19938943

Descripteurs français

English descriptors

Abstract

Cardiomyocyte apoptosis is a well-established contributor to irreversible injury following myocardial infarction (MI). Increased cardiomyocyte apoptosis is associated also with aging in animal models, exacerbated by MI; however, mechanisms for this increased sensitivity to oxidative stress are unknown. Protein mixed-disulfide formation with glutathione (protein glutathionylation) is known to change the function of intermediates that regulate apoptosis. Since glutaredoxin (Grx) specifically catalyzes protein deglutathionylation, we examined its status with aging and its influence on regulation of apoptosis. Grx1 content and activity are decreased by approximately 40% in elderly (24-mo) Fischer 344 rat hearts compared to adult (6-mo) controls. A similar extent of Grx1 knockdown in H9c2 cardiomyocytes led to increased apoptosis, decreased NFkappaB-dependent transcriptional activity, and decreased production (mRNA and protein) of anti-apoptotic NFkappaB target genes, Bcl-2 and Bcl-xL. Knockdown of Bcl-2 and/or Bcl-xL in wild-type H9c2 cells to the same extent ( approximately 50%) as observed in Grx1-knockdown cells increased baseline apoptosis; and knockdown of Bcl-xL, but not Bcl-2, also increased oxidant-induced apoptosis analogous to Grx1-knockdown cells. Natural Grx1-deficient cardiomyocytes isolated from elderly rats also displayed diminished NFkappaB activity and Bcl-xL content. Taken together, these data indicate diminution of Grx1 in elderly animals contributes to increased apoptotic susceptibility via regulation of NFkappaB function.

DOI: 10.1089/ars.2009.2791
PubMed: 19938943
PubMed Central: PMC2864653


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Le document en format XML

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<term>Aging (metabolism)</term>
<term>Animals (MeSH)</term>
<term>Apoptosis (drug effects)</term>
<term>Apoptosis (physiology)</term>
<term>Cells, Cultured (cytology)</term>
<term>Cells, Cultured (drug effects)</term>
<term>Cells, Cultured (metabolism)</term>
<term>Gene Expression Regulation (drug effects)</term>
<term>Gene Expression Regulation (physiology)</term>
<term>Gene Knockdown Techniques (MeSH)</term>
<term>Genes, bcl-2 (MeSH)</term>
<term>Glutaredoxins (antagonists & inhibitors)</term>
<term>Glutaredoxins (genetics)</term>
<term>Glutaredoxins (physiology)</term>
<term>Hydrogen Peroxide (pharmacology)</term>
<term>Male (MeSH)</term>
<term>Myocardium (metabolism)</term>
<term>Myocytes, Cardiac (cytology)</term>
<term>Myocytes, Cardiac (drug effects)</term>
<term>Myocytes, Cardiac (metabolism)</term>
<term>NF-kappa B (antagonists & inhibitors)</term>
<term>NF-kappa B (physiology)</term>
<term>Oxidation-Reduction (MeSH)</term>
<term>Proto-Oncogene Proteins c-bcl-2 (biosynthesis)</term>
<term>Proto-Oncogene Proteins c-bcl-2 (genetics)</term>
<term>Proto-Oncogene Proteins c-bcl-2 (physiology)</term>
<term>RNA, Messenger (biosynthesis)</term>
<term>RNA, Small Interfering (pharmacology)</term>
<term>Rats (MeSH)</term>
<term>Rats, Inbred F344 (MeSH)</term>
<term>bcl-X Protein (biosynthesis)</term>
<term>bcl-X Protein (genetics)</term>
<term>bcl-X Protein (physiology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>ARN messager (biosynthèse)</term>
<term>Animaux (MeSH)</term>
<term>Apoptose (effets des médicaments et des substances chimiques)</term>
<term>Apoptose (physiologie)</term>
<term>Cellules cultivées (cytologie)</term>
<term>Cellules cultivées (effets des médicaments et des substances chimiques)</term>
<term>Cellules cultivées (métabolisme)</term>
<term>Facteur de transcription NF-kappa B (antagonistes et inhibiteurs)</term>
<term>Facteur de transcription NF-kappa B (physiologie)</term>
<term>Glutarédoxines (antagonistes et inhibiteurs)</term>
<term>Glutarédoxines (génétique)</term>
<term>Glutarédoxines (physiologie)</term>
<term>Gènes bcl-2 (MeSH)</term>
<term>Myocarde (métabolisme)</term>
<term>Myocytes cardiaques (cytologie)</term>
<term>Myocytes cardiaques (effets des médicaments et des substances chimiques)</term>
<term>Myocytes cardiaques (métabolisme)</term>
<term>Mâle (MeSH)</term>
<term>Oxydoréduction (MeSH)</term>
<term>Peroxyde d'hydrogène (pharmacologie)</term>
<term>Petit ARN interférent (pharmacologie)</term>
<term>Protéine bcl-X (biosynthèse)</term>
<term>Protéine bcl-X (génétique)</term>
<term>Protéine bcl-X (physiologie)</term>
<term>Protéines proto-oncogènes c-bcl-2 (biosynthèse)</term>
<term>Protéines proto-oncogènes c-bcl-2 (génétique)</term>
<term>Protéines proto-oncogènes c-bcl-2 (physiologie)</term>
<term>Rats (MeSH)</term>
<term>Rats de lignée F344 (MeSH)</term>
<term>Régulation de l'expression des gènes (effets des médicaments et des substances chimiques)</term>
<term>Régulation de l'expression des gènes (physiologie)</term>
<term>Techniques de knock-down de gènes (MeSH)</term>
<term>Vieillissement (métabolisme)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en">
<term>Glutaredoxins</term>
<term>NF-kappa B</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en">
<term>Proto-Oncogene Proteins c-bcl-2</term>
<term>RNA, Messenger</term>
<term>bcl-X Protein</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr">
<term>Facteur de transcription NF-kappa B</term>
<term>Glutarédoxines</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr">
<term>ARN messager</term>
<term>Protéine bcl-X</term>
<term>Protéines proto-oncogènes c-bcl-2</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr">
<term>Cellules cultivées</term>
<term>Myocytes cardiaques</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en">
<term>Cells, Cultured</term>
<term>Myocytes, Cardiac</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>Apoptosis</term>
<term>Cells, Cultured</term>
<term>Gene Expression Regulation</term>
<term>Myocytes, Cardiac</term>
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<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr">
<term>Apoptose</term>
<term>Cellules cultivées</term>
<term>Myocytes cardiaques</term>
<term>Régulation de l'expression des gènes</term>
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<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>Glutaredoxins</term>
<term>Proto-Oncogene Proteins c-bcl-2</term>
<term>bcl-X Protein</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Glutarédoxines</term>
<term>Protéine bcl-X</term>
<term>Protéines proto-oncogènes c-bcl-2</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Aging</term>
<term>Cells, Cultured</term>
<term>Myocardium</term>
<term>Myocytes, Cardiac</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Cellules cultivées</term>
<term>Myocarde</term>
<term>Myocytes cardiaques</term>
<term>Vieillissement</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr">
<term>Peroxyde d'hydrogène</term>
<term>Petit ARN interférent</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en">
<term>Hydrogen Peroxide</term>
<term>RNA, Small Interfering</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr">
<term>Apoptose</term>
<term>Facteur de transcription NF-kappa B</term>
<term>Glutarédoxines</term>
<term>Protéine bcl-X</term>
<term>Protéines proto-oncogènes c-bcl-2</term>
<term>Régulation de l'expression des gènes</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en">
<term>Apoptosis</term>
<term>Gene Expression Regulation</term>
<term>Glutaredoxins</term>
<term>NF-kappa B</term>
<term>Proto-Oncogene Proteins c-bcl-2</term>
<term>bcl-X Protein</term>
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<keywords scheme="MESH" xml:lang="en">
<term>Animals</term>
<term>Gene Knockdown Techniques</term>
<term>Genes, bcl-2</term>
<term>Male</term>
<term>Oxidation-Reduction</term>
<term>Rats</term>
<term>Rats, Inbred F344</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Animaux</term>
<term>Gènes bcl-2</term>
<term>Mâle</term>
<term>Oxydoréduction</term>
<term>Rats</term>
<term>Rats de lignée F344</term>
<term>Techniques de knock-down de gènes</term>
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<div type="abstract" xml:lang="en">Cardiomyocyte apoptosis is a well-established contributor to irreversible injury following myocardial infarction (MI). Increased cardiomyocyte apoptosis is associated also with aging in animal models, exacerbated by MI; however, mechanisms for this increased sensitivity to oxidative stress are unknown. Protein mixed-disulfide formation with glutathione (protein glutathionylation) is known to change the function of intermediates that regulate apoptosis. Since glutaredoxin (Grx) specifically catalyzes protein deglutathionylation, we examined its status with aging and its influence on regulation of apoptosis. Grx1 content and activity are decreased by approximately 40% in elderly (24-mo) Fischer 344 rat hearts compared to adult (6-mo) controls. A similar extent of Grx1 knockdown in H9c2 cardiomyocytes led to increased apoptosis, decreased NFkappaB-dependent transcriptional activity, and decreased production (mRNA and protein) of anti-apoptotic NFkappaB target genes, Bcl-2 and Bcl-xL. Knockdown of Bcl-2 and/or Bcl-xL in wild-type H9c2 cells to the same extent ( approximately 50%) as observed in Grx1-knockdown cells increased baseline apoptosis; and knockdown of Bcl-xL, but not Bcl-2, also increased oxidant-induced apoptosis analogous to Grx1-knockdown cells. Natural Grx1-deficient cardiomyocytes isolated from elderly rats also displayed diminished NFkappaB activity and Bcl-xL content. Taken together, these data indicate diminution of Grx1 in elderly animals contributes to increased apoptotic susceptibility via regulation of NFkappaB function.</div>
</front>
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<Month>07</Month>
<Day>27</Day>
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<Month>Jun</Month>
<Day>15</Day>
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<Title>Antioxidants & redox signaling</Title>
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<ArticleTitle>Glutaredoxin regulates apoptosis in cardiomyocytes via NFkappaB targets Bcl-2 and Bcl-xL: implications for cardiac aging.</ArticleTitle>
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<AbstractText>Cardiomyocyte apoptosis is a well-established contributor to irreversible injury following myocardial infarction (MI). Increased cardiomyocyte apoptosis is associated also with aging in animal models, exacerbated by MI; however, mechanisms for this increased sensitivity to oxidative stress are unknown. Protein mixed-disulfide formation with glutathione (protein glutathionylation) is known to change the function of intermediates that regulate apoptosis. Since glutaredoxin (Grx) specifically catalyzes protein deglutathionylation, we examined its status with aging and its influence on regulation of apoptosis. Grx1 content and activity are decreased by approximately 40% in elderly (24-mo) Fischer 344 rat hearts compared to adult (6-mo) controls. A similar extent of Grx1 knockdown in H9c2 cardiomyocytes led to increased apoptosis, decreased NFkappaB-dependent transcriptional activity, and decreased production (mRNA and protein) of anti-apoptotic NFkappaB target genes, Bcl-2 and Bcl-xL. Knockdown of Bcl-2 and/or Bcl-xL in wild-type H9c2 cells to the same extent ( approximately 50%) as observed in Grx1-knockdown cells increased baseline apoptosis; and knockdown of Bcl-xL, but not Bcl-2, also increased oxidant-induced apoptosis analogous to Grx1-knockdown cells. Natural Grx1-deficient cardiomyocytes isolated from elderly rats also displayed diminished NFkappaB activity and Bcl-xL content. Taken together, these data indicate diminution of Grx1 in elderly animals contributes to increased apoptotic susceptibility via regulation of NFkappaB function.</AbstractText>
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