Earticle

초록

영어

To explore the role of histone deactylase (HDAC) activation in an in vivo model of hypertrophy, we studied the effects of Trichostatin A (TSA). TSA subjected to thoracic aortic banding (TAB)-induced pressure stress in mice. In histological observations, TAB in treated mice showed a significant hypertrophic response, whereas the sham operation remained nearly normal structure with partially blunted hypertrophy. TSA treatment had no effect (measured as HW/BW) on sham-operated animals. TAB animals treated with vehicle manifested a robust ～50% hypertrophic response (p<0.05 vs sham). TAB mice treated with 2 mg/kg/day TSA manifested a blunted growth responses, which was significantly diminished (p<0.05) compared with vehicle-treated TAB mice. TAB mice treated with a lower dose of TSA (0.5 mg/kg/day) manifested a similar blunting of hypertrophic growth (～25% increase in heart mass). Furthermore, to determine activity duration of TSA in vitro, 1 nM TSA was added to H9c2 cells. Histone acetylation was initiated at 4 hr after treatment, and it was peak up to 18 hr, then followed by significantly reduced to 30 hr. We also analyzed the expression of p53 following TSA treatment, wherein p53 expression was elevated at 4 hr, and it was maintained to 24 hr after treatment. ERK was activated at 8 hr, and maintained till 30 hr after treatment suggesting an intracellular signaling interaction between TSA and p53 expression. Taken together, it is suggested that HDAC activation is required for pressure-overload growth of the heart. Eventually, these data suggest that histone acetylation may be a novel target for therapeutic intervention in pressure-overloaded cardiac hypertrophy.

목차

ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
  Materials
  Animal Surgery
  Histological Staining
  Immunoblot Analysis
  Statistical Analysis
 RESULTS
  TSA Diminishes the TAB-Induced Cardiac Hypertrophy
  HDAC Suppression by TSA Leads to Dose-Responsive Blunted of Pathologic Cardiac Growth
  Immunoblot Analysis on Histone Acetylation
  Duration of Histone H3 Activity by TSA in H9c2 Cells
 DISCUSSION
 REFERENCES

키워드

저자

• Yunkyung Hong [ Department Rehabilitation Science in Interdisciplinary PhD Program, Graduate School of Inje University ]
• Jongwook Song [ Cardiovascular and Metabolic Disease Center, College of Biomedical Science and Engineering ]
• Sang-Kil Lee [ Cardiovascular and Metabolic Disease Center, College of Biomedical Science and Engineering ]
• Youngjeon Lee [ Department Rehabilitation Science in Interdisciplinary PhD Program, Graduate School of Inje University ]
• Gyu-Jin Rho [ Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University ]
• Joo-Heon Kim [ Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University ]
• Yonggeun Hong [ Department Rehabilitation Science in Interdisciplinary PhD Program, Graduate School of Inje University, Cardiovascular and Metabolic Disease Center, College of Biomedical Science and Engineering ] Corresponding author

참고문헌

발행기관

간행물

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• 간행물명

  Reproductive & developmental biology

• 간기

  계간

• pISSN

  1738-2432

• eISSN

  2288-0151

• 수록기간

  1977~2018

• 십진분류

  KDC 527 DDC 636