Protective effect of p53 in vascular smooth muscle cells against nitric oxide-induced apoptosis is mediated by up-regulation of heme oxygenase-2

Young Myeong Kim, Byung Min Choi, Yong Seok Kim, Young Guen Kwon, Melina R. Kibbe, Timothy R. Billiar, Edith Tzeng

Research output: Contribution to journalArticle

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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-acetylpenicillamine (SNAP) increased apoptotic cell death in p53-deficient VSMCs compared with wild-type cells. The heme oxygenase (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.

Original languageEnglish
Pages (from-to)164-169
Number of pages6
JournalJournal of Biochemistry and Molecular Biology
Volume41
Issue number2
Publication statusPublished - 2008 Feb 1

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S-Nitroso-N-Acetylpenicillamine
Vascular Smooth Muscle
Smooth Muscle Myocytes
Muscle
Nitric Oxide
Up-Regulation
Cells
Apoptosis
Cell death
Cell Death
Iron
Biliverdine
Heme Oxygenase (Decyclizing)
Heme Oxygenase-1
Nitric Oxide Donors
heme oxygenase-2
Carbon Monoxide
Tumor Suppressor Genes
Sulfur
Tumors

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

Kim, Young Myeong ; Choi, Byung Min ; Kim, Yong Seok ; Kwon, Young Guen ; Kibbe, Melina R. ; Billiar, Timothy R. ; Tzeng, Edith. / Protective effect of p53 in vascular smooth muscle cells against nitric oxide-induced apoptosis is mediated by up-regulation of heme oxygenase-2. In: Journal of Biochemistry and Molecular Biology. 2008 ; Vol. 41, No. 2. pp. 164-169.
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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-acetylpenicillamine (SNAP) increased apoptotic cell death in p53-deficient VSMCs compared with wild-type cells. The heme oxygenase (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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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; Choi, Byung Min; Kim, Yong Seok; Kwon, Young Guen; Kibbe, Melina R.; Billiar, Timothy R.; Tzeng, Edith.

In: Journal of Biochemistry and Molecular Biology, Vol. 41, No. 2, 01.02.2008, p. 164-169.

Research output: Contribution to journalArticle

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