Senescence marker protein 30 has a cardio-protective role in doxorubicin-induced cardiac dysfunction
| العنوان: | Senescence marker protein 30 has a cardio-protective role in doxorubicin-induced cardiac dysfunction |
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| المؤلفون: | Shu-ichi Saitoh, Makiko Miyata, Yasuchika Takeishi, Tetsuro Shishido, Akihito Ishigami, Isao Kubota, Satoshi Suzuki, Tomofumi Misaka |
| المصدر: | PLoS ONE, Vol 8, Iss 12, p e79093 (2013) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, Aging, Anatomy and Physiology, Mouse, lcsh:Medicine, Apoptosis, Ascorbic Acid, medicine.disease_cause, Toxicology, Cardiovascular, Cardiovascular System, Diagnostic Radiology, Mice, Fibrosis, Molecular Cell Biology, polycyclic compounds, Myocytes, Cardiac, Phosphorylation, lcsh:Science, bcl-2-Associated X Protein, Cellular Stress Responses, Mice, Knockout, Multidisciplinary, biology, Cell Death, Caspase 3, Intracellular Signaling Peptides and Proteins, Animal Models, Up-Regulation, Proto-Oncogene Proteins c-bcl-2, Echocardiography, Medicine, Cardiomyopathies, Radiology, medicine.drug, Signal Transduction, Research Article, Senescence, medicine.medical_specialty, Cardiotonic Agents, Histology, Toxic Agents, Mice, Transgenic, macromolecular substances, Cardiovascular Pharmacology, Bcl-2-associated X protein, Model Organisms, Downregulation and upregulation, Internal medicine, medicine, Animals, Doxorubicin, Biology, Heart Failure, Myocardium, Calcium-Binding Proteins, lcsh:R, Stroke Volume, medicine.disease, Ascorbic acid, Mice, Inbred C57BL, carbohydrates (lipids), Oxidative Stress, Endocrinology, biology.protein, Cancer research, lcsh:Q, Reactive Oxygen Species, Oxidative stress, Biomarkers, DNA Damage |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::88da9fe40ab8d7ee6557abc29fd84d1aTest http://europepmc.org/articles/PMC3876969?pdf=renderTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....88da9fe40ab8d7ee6557abc29fd84d1a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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