Inhibition of p53, p21 and Bax by pifithrin-α does not affect UV induced apoptotic response in CS-B cells

Cockayne syndrome (CS) is a human autosomal recessive disorder characterized by many neurological and developmental abnormalities. CS cells are defective in transcription coupled repair (TCR) pathway that removes DNA damage from the transcribed strand of active genes. In spite of a TCR deficiency at...

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Bibliographic Details
Published in:DNA repair 2003-08, Vol.2 (8), p.891-900
Main Authors: Proietti De Santis, Luca, Balajee, Adayabalam S., Lorenti Garcia, Claudia, Pepe, Gaetano, Worboys, Ana Montes, Palitti, Fabrizio
Format: Article
Language:English
Subjects:
Apoptosis - genetics
Apoptosis - radiation effects
bcl-2-Associated X Protein
Benzothiazoles
Biological and medical sciences
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Cells, Cultured
Cockayne Syndrome - genetics
CS-B cells
Electrophoresis, Polyacrylamide Gel
Fluorescent Antibody Technique
Fundamental and applied biological sciences. Psychology
Humans
Immunoblotting
Molecular and cellular biology
p53
Pifithrin-α
Proto-Oncogene Proteins - antagonists & inhibitors
Proto-Oncogene Proteins c-bcl-2
rho GTP-Binding Proteins - antagonists & inhibitors
Thiazoles - pharmacology
Toluene - analogs & derivatives
Toluene - pharmacology
Transcriptional Activation - drug effects
Tumor Suppressor Protein p53 - antagonists & inhibitors
Ultraviolet Rays
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Summary:Cockayne syndrome (CS) is a human autosomal recessive disorder characterized by many neurological and developmental abnormalities. CS cells are defective in transcription coupled repair (TCR) pathway that removes DNA damage from the transcribed strand of active genes. In spite of a TCR deficiency at the cellular level, CS patients do not develop cancer. The lack of cancer incidence in CS patients may be due to the selective elimination of cells by an apoptotic pathway. In order to verify the role of p53-associated pathway in ultraviolet (UV) induced apoptosis in human CS-B cells, the expression of p53 and p53 responsive genes was analysed in UV irradiated human cells after treatment with pifithrin-α (PFTα). PTFα effectively inhibited the induction of p53, p21 and Bax after UV treatment without affecting the apoptotic response in CS-B cells. Our results indicate that the p53-associated pathway involving p21 and Bax does not largely contribute to UV induced apoptosis in TCR defective human CS-B cells.
ISSN:1568-7864
1568-7856
DOI:10.1016/S1568-7864(03)00088-0