| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Research Abstract |
High Mobility Group Box 1 (HMGB1) is an abundant and ubiquitous nuclear DNA-binding protein that has multiple functions dependent on its cellular location. In the nucleus, HMGB1 binds to DNA, facilitating numerous nuclear functions including maintenance of genome stability, transcription and repair. However, little is known about the effects of nuclear HMGB1 on cardiac hypertrophy and heart failure. The aim of this study was to examine whether nuclear HMGB1 modifies the development of cardiac hypertrophy induced by pressure overload. Thoracic transverse aortic constriction (TAC) was created in transgenic mice with cardiac-specific overexpression of HMGB1 (HMGB1-TG) and wild type (WT) mice. Cardiac hypertrophy after TAC was attenuated in HMGB1-TG mice and survival rate after TAC was higher in HMGB1-TG mice than in WT mice. Induction of fetal cardiac genes was decreased in HMGB1-TG mice than in WT mice. Nuclear HMGB1 expression was preserved in HMGB1-TG mice compared with WT mice after TAC. Preserved nuclear HMGB1 expression significantly attenuated histone deacetylase (HDAC) activity and DNA damage after TAC. In conclusion, these results suggest that preserved nuclear HMGB1 prevents hypertrophy and heart failure via repressing HDAC activity and DNA damage.
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