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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Protective effect of p53 in vascular smooth muscle cells against nitric oxide-induced apoptosis is mediated by up-regulation of heme oxygenase-2

  • Kim, Young-Myeong (Vascular System Research Center and Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University) ;
  • Choi, Byung-Min (Department of Surgery, University of Pittsburgh Medical Center) ;
  • Kim, Yong-Seok (Department of Surgery, Chung-Ang University College of Medicine) ;
  • Kwon, Young-Guen (Department of Biochemistry, College of Sciences, Yonsei University) ;
  • Kibbe, Melina R. (Department of Surgery, University of Pittsburgh Medical Center) ;
  • Billiar, Timothy R. (Department of Surgery, University of Pittsburgh Medical Center) ;
  • Tzeng, Edith (Department of Surgery, University of Pittsburgh Medical Center)
  • Received : 2007.12.24
  • Accepted : 2007.12.24
  • Published : 2008.02.29
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Abstract

The tumor suppressor gene p53 regulates apoptotic cell death and the cell cycle. In this study, we investigated the role of p53 in nitric oxide (NO)-induced apoptosis in vascular smooth muscle cells (VSMCs). We found that the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) increased apoptotic cell death in p53-deficient VSMCs compared with wild-type cells. The heme oxygen-ase (HO) inhibitor tin protoporphyrin IX reduced the resistance of wild-type VSMCs to SNAP-induced cell death. SNAP promoted HO-1 expression in both cell types. HO-2 protein was increased only in wild-type VSMCs following SNAP treatment; however, similar levels of HO-2 mRNA were detected in both cell types. SNAP significantly increased the levels of non-heme-iron and dinitrosyl iron-sulfur clusters in wild-type VSMCs compared with p53-deficient VSMCs. Moreover, pretreatment with FeSO4 and the carbon monoxide donor CORM-2, but not biliverdin, significantly protected p53-deficient cells from SNAP-induced cell death compared with normal cells. These results suggest that wild-type VSMCs are more resistant to NO-mediated apoptosis than p53-deficient VSMCs through p53-dependent up-regulation of HO-2.

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References

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