Chronic akt activation accentuates aging-induced cardiac hypertrophy and myocardial contractile dysfunction: role of autophagy
| العنوان: | Chronic akt activation accentuates aging-induced cardiac hypertrophy and myocardial contractile dysfunction: role of autophagy |
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| المؤلفون: | Asli F. Ceylan-Isik, Jennifer M. Nunn, Yingmei Zhang, Loren E. Wold, Yinan Hua, Jun Ren |
| المصدر: | Basic Research in Cardiology. 106:1173-1191 |
| بيانات النشر: | Springer Science and Business Media LLC, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Aging, medicine.medical_specialty, Physiology, Blotting, Western, ATG5, Cardiomegaly, Mice, Transgenic, Biology, Mice, Physiology (medical), Internal medicine, Autophagy, medicine, Animals, Myocyte, PTEN, Protein kinase B, PI3K/AKT/mTOR pathway, AMPK, Myocardial Contraction, Enzyme Activation, Endocrinology, Echocardiography, biology.protein, Phosphorylation, Cardiology and Cardiovascular Medicine, Proto-Oncogene Proteins c-akt |
| الوصف: | Aging is often accompanied with geometric and functional changes in the heart, although the underlying mechanisms remain unclear. Recent evidence has described a potential role of Akt and autophagy in aging-associated organ deterioration. This study was to examine the impact of cardiac-specific Akt activation on aging-induced cardiac geometric and functional changes and underlying mechanisms involved. Cardiac geometry, contractile and intracellular Ca(2+) properties were evaluated using echocardiography, edge-detection and fura-2 techniques. Level of insulin signaling and autophagy was evaluated by western blot. Our results revealed cardiac hypertrophy (enlarged chamber size, wall thickness, myocyte cross-sectional area), fibrosis, decreased cardiac contractility, prolonged relengthening along with compromised intracellular Ca(2+) release and clearance in aged (24-26 month-old) mice compared with young (3-4 month-old) mice, the effects of which were accentuated by chronic Akt activation. Aging enhanced Akt and mTOR phosphorylation while reducing that of PTEN, AMPK and ACC with a more pronounced response in Akt transgenic mice. GSK3β phosphorylation and eNOS levels were unaffected by aging or Akt overexpression. Levels of beclin-1, Atg5 and LC3-II-to-LC3-I ratio were decreased in aged hearts, the effect of which with the exception of Atg 5 was exacerbated by Akt overactivation. Levels of p62 were significantly enhanced in aged mice with a more pronounced increase in Akt mice. Neither aging nor Akt altered β-glucuronidase activity and cathepsin B although aging reduced LAMP1 level. In addition, rapamycin reduced aging-induced cardiomyocyte contractile and intracellular Ca(2+) dysfunction while Akt activation suppressed autophagy in young but not aged cardiomyocytes. In conclusion, our data suggest that Akt may accentuate aging-induced cardiac geometric and contractile defects through a loss of autophagic regulation. |
| تدمد: | 1435-1803 0300-8428 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6d2f39c2ac39a224649022e7f1798493 https://doi.org/10.1007/s00395-011-0222-8 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....6d2f39c2ac39a224649022e7f1798493 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14351803 03008428 |
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