期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 90, 期 6, 页码 1098-1111出版社
WILEY
DOI: 10.1002/jcb.10736
关键词
bilirubin; oxidative stress; cyclin; gene profiling; cell proliferation; quantitative real-time RT-PCR
资金
- NHLBI NIH HHS [HL55601] Funding Source: Medline
- PHS HHS [34300] Funding Source: Medline
The purpose of the present study was to examine the role of human hemeoxygenase (human HO-1) in cell cycle progression following exposure to heme or human HO-1 gene transfer and to identify target genes associated with human HO-1-meditated increases in cell cycle progression using cDNA microarray technology. Heme-induced robust human HO-1 expression in quiescent human microvessel enclothelial cells cultured in 1% FBS and the levels of human HO-1 expression progressively declined without a change in the cell cyclin. To identify genes regulated by human HO-1 in the cell cycle, human enclothelial cells were transcluced with a retroviral vector encoded with human HO-1 gene or an empty vector. Transgene expression and functionality of the recombinant protein were assessed by Western blotting, enzyme activity, carbon monoxide, cGMP production, and cell cycle analysis. Human cDNA gene array and quantitative real-time RT-PCR were used to identify both known and novel differentially expressed genes in cells overexpressing human HO-1. Major findings were upregulation of several genes associated with cell cycle progression, including cyclin E and D; downregulation of cyclin-dependent kinase inhibitors p21 and p27, cyclin-dependent kinases 2, 5, and 6, and monocyte chemoattractant protein-1; and upregulation of growth factors, including vascular enclothelial growth factor (VEGF) and vascular enclothelial growth factor receptor I (VEGFRI), enclothelial growth factor (EGF) and hepatic-derived growth factor (HDGF). These findings identify an array of gene responses to overexpression of human HO-1 and elucidate new aspects of human HO-1 signaling involved in cell growth. (C) 2003 Wiley-Liss, Inc.
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