Human 8-oxoguanine DNA glycosylase increases resistance to hyperoxic cytotoxicity in lung epithelial cells and involvement with altered MAPK activity.
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.
Kannan
S
S
1Department of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences, Grand Forks ND58203, China.
Pang
H
H
Foster
D C
DC
Rao
Z
Z
Wu
M
M
D015153:Blotting, Western; D016923:Cell Death / Q000502:physiology*; D002460:Cell Line; D004249:DNA Damage / Q000502:physiology; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D006801:Humans; D018496:Hyperoxia / Q000503:physiopathology; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D020545:Respiratory Mucosa / Q000201:enzymology* / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D014161:Transduction, Genetic; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000502:physiology
D004268:DNA-Binding Proteins; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human