1. ¹Department of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences, Grand Forks ND58203, China
2. ²Laboratory of Structural Biology, Tsinghua University, Beijing 100084, China
3. ³National Laboratory of Bio-Macromolecules, Institute of Biophysics, Beijing 100101, China

Correspondence: M Wu, Department of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences, 501 N Columbia Road, Room 2726, UND, PO Box 9037, Grand Forks, ND58203, China. Tel: +86-701-777-4875; Fax: +86-701-777-2382; E-mail: minwu@medicine.nodak.edu

Received 12 April 2005; Revised 23 May 2005; Accepted 15 June 2005; Published online 29 July 2005.

Abstract

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% O₂. p38 activity in A549 cells was also increased by exposure to 95% O₂. 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.