Age-related changes of forkhead transcription factor FOXO1 in the liver of senescence-accelerated mouse SAMP8
| Autor: | Yoshie Kawashima-Ohya, Tatsuo Shinozuka, Koji Tomobe, Tsuyoshi Kawashima, Yasuyuki Nomura |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Senescence endocrine system Aging medicine.medical_specialty Health (social science) Blotting Western FOXO1 Polymerase Chain Reaction Receptor IGF Type 1 Mice Internal medicine medicine Animals Protein Phosphatase 2 Phosphorylation Receptor Protein kinase B biology Forkhead Box Protein O1 Superoxide Dismutase Chemistry Forkhead Transcription Factors Protein phosphatase 2 Accelerated aging Mice Mutant Strains Oncogene Protein v-akt Endocrinology Liver Catalase biology.protein Geriatrics and Gerontology Gerontology hormones hormone substitutes and hormone antagonists |
| Zdroj: | Archives of Gerontology and Geriatrics. 57:417-422 |
| ISSN: | 0167-4943 |
| DOI: | 10.1016/j.archger.2013.06.004 |
| Popis: | SAMP8 exhibits accelerated aging and a short lifespan. Insulin-like growth factor-1 receptor (IGF-1R)/FOXO pathway is associated with aging. Phosphorylation of IGF-1R, Akt, and FOXO1 was found to be increased during aging in the liver of SAMR1 normal aging mice. However, significant decreases in the phosphorylation of IGF-1R and Akt were observed in the liver of SAMP8 during aging compared with that in SAMR1, whereas phosphorylation of FOXO1 was markedly increased with age in SAMP8. In addition, the protein level of FOXO1 was decreased with age in SAMP8. Protein phosphatase 2A (PP2A) directly dephosphorylates FOXO1. Significant reduction of PP2A activity was observed in the liver nucleus of SAMP8. These results suggest the possibility that the increased FOXO1 phosphorylation might occur by the decreased activity of PP2A, resulting in the decrease in the protein level of FOXO1 in SAMP8. Furthermore, FOXO1 regulates longevity and the expression of antioxidant enzymes such as Mn-SOD and catalase. The expression of Mn-SOD and catalase was significantly decreased in the liver of SAMP8. Therefore, it is possible that the elevation of phosphorylated FOXO1 level with age causes a short lifespan in SAMP8. |
| Databáze: | OpenAIRE |
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