The Role of Bcl-x(L) Protein in Nucleotide Excision Repair–Facilitated Cell Protection Against Cisplatin-Induced Apoptosis
| Autor: | Gan Wang, Stephanie L. Lomonaco, Xiaoxin S. Xu |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Alkylating Agents
Xeroderma pigmentosum DNA Repair Transcription Genetic DNA repair DNA damage Active Transport Cell Nucleus bcl-X Protein Apoptosis Biology Cell Line DDB1 Original Research Articles Genetics medicine Humans RNA Small Interfering Nuclear protein Molecular Biology Cisplatin Xeroderma Pigmentosum NF-kappa B Nuclear Proteins Cell Biology General Medicine Fibroblasts Endonucleases medicine.disease Molecular biology Xeroderma Pigmentosum Group A Protein DNA-Binding Proteins Cancer cell DNA Damage Transcription Factors Nucleotide excision repair medicine.drug |
| Zdroj: | DNA and Cell Biology. 28:285-294 |
| ISSN: | 1557-7430 1044-5498 |
| DOI: | 10.1089/dna.2008.0815 |
| Popis: | Many anticancer drugs target the genomic DNA of cancer cells by generating DNA damage and inducing apoptosis. DNA repair protects cells against DNA damage-induced apoptosis. Although the mechanisms of DNA repair and apoptosis have been extensively studied, the mechanism by which DNA repair prevents DNA damage-induced apoptosis is not fully understood. We studied the role of the antiapoptotic Bcl-x(L) protein in nucleotide excision repair (NER)-facilitated cell protection against cisplatin-induced apoptosis. Using both normal human fibroblasts (NF) and NER-defective xeroderma pigmentosum group A (XPA) and group G (XPG) fibroblasts, we demonstrated that a functional NER is required for cisplatin-induced transcription of the bcl-x(l) gene. The results obtained from our Western blots revealed that the cisplatin treatment led to an increase in the level of Bcl-x(L) protein in NF cells, but a decrease in the level of Bcl-x(L) protein in both XPA and XPG cells. The results of our immunofluorescence staining indicated that a functional NER pathway was required for cisplatin-induced translocation of NF-kappaB p65 from cytoplasm into nucleus, indicative of NF-kappaB activation. Given the important function of NF-kappaB in regulating transcription of the bcl-x(l) gene and the Bcl-x(L) protein in preventing apoptosis, these results suggest that NER may protect cells against cisplatin-induced apoptosis by activating NF-kappaB, which further induces transcription of the bcl-x(l) gene, resulting in an accumulation of Bcl-x(L) protein and activation of the cell survival pathway that leads to increased cell survival under cisplatin treatment. |
| Databáze: | OpenAIRE |
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