Human 8-oxoguanine DNA glycosylase increases resistance to hyperoxic cytotoxicity in lung epithelial cells and involvement with altered MAPK activity
| Autor: | M Wu, Z Rao, H Pang, D C Foster, Shibichakravarthy Kannan |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
MAPK/ERK pathway
Cell signaling DNA Repair DNA damage Blotting Western Respiratory Mucosa Biology Hyperoxia p38 Mitogen-Activated Protein Kinases base excision repair Article Cell Line DNA Glycosylases Transduction Genetic medicine Humans cell signaling Cytotoxicity Molecular Biology Lung Mitogen-Activated Protein Kinase 3 Cell Death Cell Biology Base excision repair respiratory system lung epithelial cells Molecular biology MAPK DNA-Binding Proteins Enzyme Activation medicine.anatomical_structure Gene Expression Regulation DNA glycosylase Mutation medicine.symptom Mitogen-Activated Protein Kinases Signal Transduction |
| Zdroj: | Cell Death and Differentiation |
| ISSN: | 1350-9047 |
| Popis: | It is unknown whether base excision DNA repair (BER) proteins interact with mitogen-activated protein kinases (MAPK) under oxidation. Here, we explored roles of BER proteins in signaling transduction involving MAPK during hyperoxia. We demonstrated that ERK1/2 phosphorylation in A549 cells was increased in 95% O(2). p38 activity in A549 cells was also increased by exposure to 95% O(2). To evaluate regulatory roles of MAPK, we have transduced A549 cells and primary alveolar epithelial type II cells (AECII) to overexpress 8-oxoguanine DNA glycosylase (hOgg1). Overexpression of hOgg1 reduced hyperoxic toxicity in A549 and AECII cells. Furthermore, protection by BER against hyperoxia appeared to involve an upregulation of ERK1/2 and downregulation of p38. These observations demonstrate, for the first time, that reduction of hyperoxic toxicity by BER proteins may be involved with MAPK activity, thereby impacting cell survival. Furthermore, our studies suggest that modulation of MAPK may be used in combination with BER proteins to counteract hyperoxic toxicity. |
| Databáze: | OpenAIRE |
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