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Senescence Marker Protein 30 Has a Cardio-Protective Role in Doxorubicin-Induced Cardiac Dysfunction

BACKGROUND: Senescence marker protein 30 (SMP30), which was originally identified as an aging marker protein, is assumed to act as a novel anti-aging factor in the liver, lungs and brain. We hypothesized that SMP30 has cardio-protective function due to its anti-aging and anti-oxidant effects on doxo...

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Autores principales: Miyata, Makiko, Suzuki, Satoshi, Misaka, Tomofumi, Shishido, Tetsuro, Saitoh, Shu-ichi, Ishigami, Akihito, Kubota, Isao, Takeishi, Yasuchika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876969/
https://www.ncbi.nlm.nih.gov/pubmed/24391705
http://dx.doi.org/10.1371/journal.pone.0079093
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author Miyata, Makiko
Suzuki, Satoshi
Misaka, Tomofumi
Shishido, Tetsuro
Saitoh, Shu-ichi
Ishigami, Akihito
Kubota, Isao
Takeishi, Yasuchika
author_facet Miyata, Makiko
Suzuki, Satoshi
Misaka, Tomofumi
Shishido, Tetsuro
Saitoh, Shu-ichi
Ishigami, Akihito
Kubota, Isao
Takeishi, Yasuchika
author_sort Miyata, Makiko
collection PubMed
description BACKGROUND: Senescence marker protein 30 (SMP30), which was originally identified as an aging marker protein, is assumed to act as a novel anti-aging factor in the liver, lungs and brain. We hypothesized that SMP30 has cardio-protective function due to its anti-aging and anti-oxidant effects on doxorubicin (DOX)-induced cardiac dysfunction. METHODS AND RESULTS: SMP30 knockout (SMP30 KO) mice, SMP30 transgenic (SMP30 TG) mice with cardiac-specific overexpression of SMP30 gene and wild-type (WT) littermate mice at 12–14 weeks of age were given intra-peritoneal injection of DOX (20 mg/kg) or saline. Five days after DOX injection, echocardiography revealed that left ventricular ejection fraction was more severely reduced in the DOX-treated SMP30 KO mice than in the DOX-treated WT mice, but was preserved in the DOX-treated SMP30 TG mice. Generation of reactive oxygen species and oxidative DNA damage in the myocardium were greater in the DOX-treated SMP30 KO mice than in the DOX-treated WT mice, but much less in the SMP30 TG mice. The numbers of deoxynucleotidyltransferase-mediated dUTP nick end-labeling positive nuclei in the myocardium, apoptotic signaling pathways such as caspase-3 activity, Bax/Bcl-2 ratio and phosphorylation activity of c-Jun N-terminal kinase were increased in SMP30 KO mice and decreased in SMP30 TG mice compared with WT mice after DOX injection. CONCLUSIONS: SMP30 has a cardio-protective role by anti-oxidative and anti-apoptotic effects in DOX-induced cardiotoxicity, and can be a new therapeutic target to prevent DOX-induced heart failure.
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spelling pubmed-38769692014-01-03 Senescence Marker Protein 30 Has a Cardio-Protective Role in Doxorubicin-Induced Cardiac Dysfunction Miyata, Makiko Suzuki, Satoshi Misaka, Tomofumi Shishido, Tetsuro Saitoh, Shu-ichi Ishigami, Akihito Kubota, Isao Takeishi, Yasuchika PLoS One Research Article BACKGROUND: Senescence marker protein 30 (SMP30), which was originally identified as an aging marker protein, is assumed to act as a novel anti-aging factor in the liver, lungs and brain. We hypothesized that SMP30 has cardio-protective function due to its anti-aging and anti-oxidant effects on doxorubicin (DOX)-induced cardiac dysfunction. METHODS AND RESULTS: SMP30 knockout (SMP30 KO) mice, SMP30 transgenic (SMP30 TG) mice with cardiac-specific overexpression of SMP30 gene and wild-type (WT) littermate mice at 12–14 weeks of age were given intra-peritoneal injection of DOX (20 mg/kg) or saline. Five days after DOX injection, echocardiography revealed that left ventricular ejection fraction was more severely reduced in the DOX-treated SMP30 KO mice than in the DOX-treated WT mice, but was preserved in the DOX-treated SMP30 TG mice. Generation of reactive oxygen species and oxidative DNA damage in the myocardium were greater in the DOX-treated SMP30 KO mice than in the DOX-treated WT mice, but much less in the SMP30 TG mice. The numbers of deoxynucleotidyltransferase-mediated dUTP nick end-labeling positive nuclei in the myocardium, apoptotic signaling pathways such as caspase-3 activity, Bax/Bcl-2 ratio and phosphorylation activity of c-Jun N-terminal kinase were increased in SMP30 KO mice and decreased in SMP30 TG mice compared with WT mice after DOX injection. CONCLUSIONS: SMP30 has a cardio-protective role by anti-oxidative and anti-apoptotic effects in DOX-induced cardiotoxicity, and can be a new therapeutic target to prevent DOX-induced heart failure. Public Library of Science 2013-12-31 /pmc/articles/PMC3876969/ /pubmed/24391705 http://dx.doi.org/10.1371/journal.pone.0079093 Text en © 2013 Miyata et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Miyata, Makiko
Suzuki, Satoshi
Misaka, Tomofumi
Shishido, Tetsuro
Saitoh, Shu-ichi
Ishigami, Akihito
Kubota, Isao
Takeishi, Yasuchika
Senescence Marker Protein 30 Has a Cardio-Protective Role in Doxorubicin-Induced Cardiac Dysfunction
title Senescence Marker Protein 30 Has a Cardio-Protective Role in Doxorubicin-Induced Cardiac Dysfunction
title_full Senescence Marker Protein 30 Has a Cardio-Protective Role in Doxorubicin-Induced Cardiac Dysfunction
title_fullStr Senescence Marker Protein 30 Has a Cardio-Protective Role in Doxorubicin-Induced Cardiac Dysfunction
title_full_unstemmed Senescence Marker Protein 30 Has a Cardio-Protective Role in Doxorubicin-Induced Cardiac Dysfunction
title_short Senescence Marker Protein 30 Has a Cardio-Protective Role in Doxorubicin-Induced Cardiac Dysfunction
title_sort senescence marker protein 30 has a cardio-protective role in doxorubicin-induced cardiac dysfunction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876969/
https://www.ncbi.nlm.nih.gov/pubmed/24391705
http://dx.doi.org/10.1371/journal.pone.0079093
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