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Identification of plasma APE1/Ref-1 in lipopolysaccharide-induced endotoxemic rats: Implication of serological biomarker for an endotoxemia

Park, Myoung Soo, Lee, Yu Ran, Choi, Sunga, Joo, Hee Kyoung, Cho, Eun Jung, Kim, Cuk Seong, Park, Jin Bong, Jo, Eun-Kyeong, Jeon, Byeong Hwa
Biochemical and biophysical research communications 2013 v.435 pp. 621-626
DNA repair, biomarkers, cell adhesion, endotoxemia, gene expression regulation, human umbilical vein endothelial cells, humans, lipopolysaccharides, liquid chromatography, nitrites, rats, tandem mass spectrometry, transcription (genetics), tumor necrosis factor-alpha
Apurinic/apyrimidinic endonuclease1/Redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in base excision DNA repair and in transcriptional regulation of gene expression. We investigated whether APE1/Ref-1 increased in plasma of endotoxemic rats. Lipopolysaccharide (LPS) was used to induce endotoxemia in rats. Administration of LPS (10mg/kg, i.p.) significantly induced plasma nitrite production and tumor necrosis factor-α (TNF-α). A 37kDa immunoreactive band was detected in cell-free plasma of LPS-treated rats using anti-APE1/Ref-1, which reached a maximum at 12h after the LPS injection. The 37kDa immunoreactive band was identified as rat APE1/Ref-1 by liquid chromatography/tandem mass spectrometry. Interestingly, treatment with recombinant human APE1/Ref-1 protein (2–5μg/ml for 18h) inhibited TNF-α-induced vascular cell adhesion molecule-1 expression in human umbilical vein endothelial cells. Taken together, the level of plasma APE1/Ref-1 increased in LPS-induced endotoxemic rats, suggesting that plasma APE1/Ref-1 might serve as a serological biomarker for endotoxemia.