title: Downregulated endogenous sulfur dioxide/aspartate aminotransferase pathway is involved in angiotensin II-stimulated cardiomyocyte autophagy and myocardial hypertrophy in mice.
abstract: BACKGROUND
  The study was designed to investigate if endogenous sulfur dioxide (SO2) was involved in cardiomyocyte autophagy and myocardial hypertrophy stimulated by angiotensin II (Ang II).
  
  
  METHODS
  Thirty-two C57 mice were randomly divided into control, SO2, Ang II and Ang II+SO2groups. Human myocardial cell line H9c2 was divided into four groups including control, SO2, Ang II and Ang II+SO2groups. Blood pressure and myocardial hypertrophy of the mice were measured two weeks after Ang II administration. LC3 II/I ratio, and Beclin1, Atg4B and p62 expressions were determined both in vivo and in vitro. Autophagosome was observed in H9c2 cells with confocal microscope. Endogenous SO2generation and aspartate aminotransferase (AAT) expression were measured.
  
  
  RESULTS
  In animal studies, hypertension and myocardial hypertrophy developed two weeks after Ang II administration. LC3 II/I ratio and Beclin1 and Atg4B expressions were markedly elevated (P all <0.05), but p62 expression was lowered (P<0.05) both in vivo and in vitro. Compared with control group, endogenous SO2levels, AAT activity and AAT2 expression were obviously down-regulated (P all <0.05). However, SO2donor significantly reduced Ang II-induced myocardial hypertrophy in mice. LC3 II/I ratio and Beclin1 and Atg4B expressions were down-regulated (P all <0.05) but p62 expression was significantly increased (P<0.05) in the presence of SO2both in vivo and in vitro.
  
  
  CONCLUSIONS
  Down-regulated endogenous SO2/AAT2 pathway might be involved in the pathogenesis of myocardial hypertrophy. SO2prevented Ang II -induced myocardial hypertrophy accompanied by down-regulating cardiomyocyte autophagy.
authors: Department of Pediatrics, Peking University First Hospital, Beijing, PR China.
authors: Qinghua
authors: Q
authors: Chen
authors: Department of Pediatrics, Peking University First Hospital, Beijing, PR China.
authors: Lulu
authors: L
authors: Zhang
authors: Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, PR China.
authors: Siyao
authors: S
authors: Chen
authors: Department of Pediatrics, Peking University First Hospital, Beijing, PR China.
authors: Yaqian
authors: Y
authors: Huang
authors: Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, PR China.
authors: Kun
authors: K
authors: Li
authors: Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, PR China.
authors: Xiaoqi
authors: X
authors: Yu
authors: Department of Pediatrics, Peking University First Hospital, Beijing, PR China.
authors: Huijuan
authors: H
authors: Wu
authors: Department of Pediatrics, Peking University First Hospital, Beijing, PR China.
authors: Xiaoyu
authors: X
authors: Tian
authors: Department of Pediatrics, Peking University First Hospital, Beijing, PR China.
authors: Chunyu
authors: C
authors: Zhang
authors: Department of Physiology and Pathophysiology, Peking University Health Science Centre, Beijing, PR China; Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing, PR China.
authors: Chaoshu
authors: C
authors: Tang
authors: Department of Pediatrics, Peking University First Hospital, Beijing, PR China.
authors: Junbao
authors: J
authors: Du
authors: Department of Pediatrics, Peking University First Hospital, Beijing, PR China; Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing, PR China. Electronic address: jinhongfang51@126.com.
authors: Hongfang
authors: H
authors: Jin
mesh_terms: D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013458:Sulfur Dioxide / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D013458:Sulfur Dioxide; D000804:Angiotensin II; D001219:Aspartate Aminotransferases
keywords: Angiotensin II; Autophagy; Myocardial hypertrophy; Sulfur dioxide