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4-Hydroxynonenal modulation of p53 family gene expression in the SK-N-BE neuroblastoma cell line
- Source :
- Free radical biologymedicine. 38(2)
- Publication Year :
- 2004
-
Abstract
- 4-Hydroxynonenal (HNE), a product of lipid peroxidation, inhibits proliferation of several tumor cells. The p53 tumor suppressor protein plays a critical role in cell cycle control, by inducing p21 expression, and in apoptosis, by inducing bax expression. Recently, two other proteins with many p53-like properties, TAp73 (p73) and TAp63 (p63), have been discovered. SK-N-BE human neuroblastoma cells express the three p53 family proteins and can be used for the study of their induction. We investigated HNE action in the control of proliferation, differentiation, and apoptosis in SK-N-BE cells and the HNE effect on the expression of p53, p63, p73, p21, bax, and G1 cyclins. Retinoic acid (RA) was used as a positive control. HNE inhibited cell proliferation without inducing differentiation; it decreased S-phase cells and increased the number of apoptotic cells. RA reduced the proportion of S-phase cells and did not induce apoptosis. HNE increased p53, p73, p63, p21, and bax expression at different time points. HNE reduced cyclin D2 expression and the phosphorylation of pRb protein. Our results demonstrated that HNE inhibits SK-N-BE cell proliferation by increasing the expression of p53 family proteins and p53 target proteins which modulate cell cycle progression and apoptosis.
- Subjects :
- p53
Time Factors
Cellular differentiation
Apoptosis
Cell Cycle Proteins
Biochemistry
Retinoblastoma Protein
chemistry.chemical_compound
Neuroblastoma
cell growth
Tumor Protein p73
Genes, Tumor Suppressor
Phosphorylation
Chromatography, High Pressure Liquid
Cyclin
bcl-2-Associated X Protein
p63
biology
Reverse Transcriptase Polymerase Chain Reaction
Cell Cycle
Nuclear Proteins
Cell Differentiation
Cell cycle
Flow Cytometry
Cell biology
Peroxides
DNA-Binding Proteins
Proto-Oncogene Proteins c-bcl-2
4-hydroxynonenal
p73
apoptosis
SK-N-BE human neuroblastoma cell line
free radicals
Cyclin-Dependent Kinase Inhibitor p21
Blotting, Western
HL-60 Cells
Tretinoin
Cysteine Proteinase Inhibitors
4-Hydroxynonenal
Bcl-2-associated X protein
Cyclin D2
Physiology (medical)
Cell Line, Tumor
Humans
Cell Proliferation
Aldehydes
Cell growth
Tumor Suppressor Proteins
Lipid Metabolism
Phosphoproteins
chemistry
Microscopy, Fluorescence
biology.protein
Cancer research
Trans-Activators
Tumor Suppressor Protein p53
Transcription Factors
Subjects
Details
- ISSN :
- 08915849
- Volume :
- 38
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Free radical biologymedicine
- Accession number :
- edsair.doi.dedup.....be56f7d3ab8bf8aa8a46bc4d2c4b8c4d