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PLoS One. 2013 Dec 31;8(12):e79093. doi: 10.1371/journal.pone.0079093. eCollection 2013.

Senescence marker protein 30 has a cardio-protective role in doxorubicin-induced cardiac dysfunction.

Author information

1
Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan.
2
First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan.
3
Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.

Abstract

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.

PMID:
24391705
PMCID:
PMC3876969
DOI:
10.1371/journal.pone.0079093
[Indexed for MEDLINE]
Free PMC Article

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