title: Regulation of PUMA induced by mechanical stress in rat cardiomyocytes.
abstract: BACKGROUND
  PUMA (p53-up-regulated modulator of apoptosis), an apoptosis regulated gene, increased during endoplasmic reticulum stress. However, the expression of PUMA in cardiomyocytes under mechanical stress is little known. We aimed to investigate the regulation mechanism of PUMA expression and apoptosis induced by mechanical stress in cardiomyocytes.
  
  
  METHODS
  Aorta-caval (AV) shunt was performed in adult Wistar rats to induce volume overload. Rat neonatal cardiomyocytes were stretched by vacuum to 20% of maximum elongation at 60 cycles/min.
  
  
  RESULTS
  PUMA protein and mRNA were up-regulated in the shunt group as compared with sham group. The increased PUMA protein expression and apoptosis induced by shunt was reversed by treatment with atorvastatin at 30 mg/kg/ day orally for 7 days. TUNEL assay showed that treatment with atorvastatin inhibited the apoptosis induced by volume overload. Cyclic stretch significantly enhanced PUMA protein and gene expression. Addition of c-jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA (siRNA) and interferon-γ (INF-γ) antibody 30 min before stretch reduced the induction of PUMA protein. Gel shift assay demonstrated that stretch increased the DNA binding activity of interferon regulatory factor-1. Stretch increased, while PUMA-Mut plasmid, SP600125 and INF-γ antibody abolished the PUMA promoter activity induced by stretch. PUMA mediated apoptosis induced by stretch was reversed by PUMA siRNA and atorvastatin.
  
  
  CONCLUSIONS
  Mechanical stress enhanced apoptosis and PUMA expression in cardiomyocytes. Treatment with atorvastatin reversed both PUMA expression and apoptosis induced by mechanical stress in cardiomyocytes.
authors.affiliation: Department of Medical Education and Research, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
authors.forename: Wen-Pin
authors.initials: WP
authors.lastname: Cheng
authors.forename: Gong-Jhe
authors.initials: GJ
authors.lastname: Wu
authors.forename: Bao-Wei
authors.initials: BW
authors.lastname: Wang
authors.forename: Kou-Gi
authors.initials: KG
authors.lastname: Shyu
mesh_terms: D000818:Animals; D001011:Aorta / Q000601:surgery; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D000069059:Atorvastatin; D001810:Blood Volume; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006538:Heptanoic Acids / Q000008:administration & dosage; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011758:Pyrroles / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013314:Stress, Mechanical
chemical_list: D051017:Apoptosis Regulatory Proteins; C533952:Bbc3 protein, rat; D006538:Heptanoic Acids; D011758:Pyrroles; D012333:RNA, Messenger; D000069059:Atorvastatin