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Mol. Cells 2013; 36(5): 439-445

Published online November 30, 2013

https://doi.org/10.1007/s10059-013-0195-6

© The Korean Society for Molecular and Cellular Biology

Cytoplasmic Localization and Redox Cysteine Residue of APE1/Ref-1 Is Associated with Anti-Inflammatory Activity in Cultured Endothelial Cells

Myoung Soo Park, Cuk-Seong Kim, Hee Kyoung Joo, Yu Ran Lee, Gun Kang, Soo Jin Kim, Sunga Choi, Sang Do Lee, Jin Bong Park, and Byeong Hwa Jeon

1Infection Signaling Network Research Center, 2Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Korea,
3These authors contributed equally to this work.

Received: July 5, 2013; Revised: August 30, 2013; Accepted: September 6, 2013

Abstract

Apurinic/apyrimidinic endonuclease1/redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in base excision DNA repair and transcriptional regulation of gene expression. APE1/Ref-1 is mainly localized in nucleus, but cytoplasmic localization has also been reported. However, the functional role of cytoplasmic APE1/Ref-1 and its redox cysteine residue is still unknown. We investigated the role of cytoplasmic APE1/Ref-1 on tumor necrosis factor-α (TNF-α)-induced vascular cell adhesion molecule-1 (VCAM-1) expressions in endothelial cells. Endogenous APE1/Ref- 1 was mainly observed in nucleus, however, cytoplasmic APE1/Ref-1 was increased by TNF-α. Cytoplasmic APE1/Ref-1 expression was not blunted by cycloheximide, a protein synthesis inhibitor, suggesting cytoplasmic translocation of APE1/Ref-1. Transfection of a N-terminus deletion mutant APE1/Ref-1(29-318) inhibited TNF-α-induced VCAM-1 expression, indicating an anti-inflammatory role for APE1/Ref-1 in cytoplasm. In contrast, redox mutant of APE1/Ref-1 (C65A/C93A) transfection led to increased TNF-α-induced VCAM-1 expression. Our findings suggest cytoplasmic APE1/Ref-1 localization and redox cysteine residues of APE1/Ref-1 are associated with anti-inflammatory activity in endothelial cells.

Keywords APE1/Ref-1, endothelial cells, TNF-α, VCAM-1

Article

Research Article

Mol. Cells 2013; 36(5): 439-445

Published online November 30, 2013 https://doi.org/10.1007/s10059-013-0195-6

Copyright © The Korean Society for Molecular and Cellular Biology.

Cytoplasmic Localization and Redox Cysteine Residue of APE1/Ref-1 Is Associated with Anti-Inflammatory Activity in Cultured Endothelial Cells

Myoung Soo Park, Cuk-Seong Kim, Hee Kyoung Joo, Yu Ran Lee, Gun Kang, Soo Jin Kim, Sunga Choi, Sang Do Lee, Jin Bong Park, and Byeong Hwa Jeon

1Infection Signaling Network Research Center, 2Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Korea,
3These authors contributed equally to this work.

Received: July 5, 2013; Revised: August 30, 2013; Accepted: September 6, 2013

Abstract

Apurinic/apyrimidinic endonuclease1/redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in base excision DNA repair and transcriptional regulation of gene expression. APE1/Ref-1 is mainly localized in nucleus, but cytoplasmic localization has also been reported. However, the functional role of cytoplasmic APE1/Ref-1 and its redox cysteine residue is still unknown. We investigated the role of cytoplasmic APE1/Ref-1 on tumor necrosis factor-α (TNF-α)-induced vascular cell adhesion molecule-1 (VCAM-1) expressions in endothelial cells. Endogenous APE1/Ref- 1 was mainly observed in nucleus, however, cytoplasmic APE1/Ref-1 was increased by TNF-α. Cytoplasmic APE1/Ref-1 expression was not blunted by cycloheximide, a protein synthesis inhibitor, suggesting cytoplasmic translocation of APE1/Ref-1. Transfection of a N-terminus deletion mutant APE1/Ref-1(29-318) inhibited TNF-α-induced VCAM-1 expression, indicating an anti-inflammatory role for APE1/Ref-1 in cytoplasm. In contrast, redox mutant of APE1/Ref-1 (C65A/C93A) transfection led to increased TNF-α-induced VCAM-1 expression. Our findings suggest cytoplasmic APE1/Ref-1 localization and redox cysteine residues of APE1/Ref-1 are associated with anti-inflammatory activity in endothelial cells.

Keywords: APE1/Ref-1, endothelial cells, TNF-α, VCAM-1

Mol. Cells
Jun 30, 2022 Vol.45 No.6, pp. 353~434
COVER PICTURE
ERα is modified by UFM1 and this modification (ufmylation) plays a crucial role in promoting the stability of ERα and breast cancer development. However, when ERα is deufmylated and then ubiquitinated, it disappears by proteasome-mediated degradation (Yoo et al., pp. 425-434).

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