Song Yun Jeong, Lee Ji Young, Joo Hee Kyoung, Kim Hyo Shin, Lee Sang Ki, Lee Kwon Ho, Cho Chung-Hyun, Park Jin Bong, Jeon Byeong Hwa
Research Institute of Medical Sciences, Department of Physiology, College of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-gu, Daejeon 301-131, Republic of Korea.
Biochem Biophys Res Commun. 2008 Mar 28;368(1):68-73. doi: 10.1016/j.bbrc.2008.01.037. Epub 2008 Jan 17.
Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/ref-1) is a multifunctional protein involved both in DNA base excision repair and redox regulation. In this study we evaluated the protective role of Tat-mediated APE1/ref-1 transduction on the tumor necrosis factor (TNF)-alpha-activated endothelial activation in cultured human umbilical vein endothelial cells. To construct Tat-APE1/ref-1 fusion protein, human full length of APE1/ref-1 was fused with Tat-protein transduction domain. Purified Tat-APE1/ref-1 fusion protein efficiently transduced cultured endothelial cells in a dose-dependent manner and reached maximum expression at 1h after incubation. Transduced Tat-APE1/ref-1 showed inhibitory activity on the TNF-alpha-induced monocyte adhesion and vascular cell adhesion molecule-1 expression in cultured endothelial cells. These results suggest Tat-APE1/ref-1 might be useful to reduce vascular endothelial activation or vascular inflammatory disorders.
脱嘌呤/脱嘧啶核酸内切酶1/氧化还原因子-1（APE1/ref-1）是一种多功能蛋白，参与DNA碱基切除修复和氧化还原调节。在本研究中，我们评估了Tat介导的APE1/ref-1转导对培养的人脐静脉内皮细胞中肿瘤坏死因子（TNF）-α激活的内皮细胞活化的保护作用。为构建Tat-APE1/ref-1融合蛋白，将人全长APE1/ref-1与Tat蛋白转导结构域融合。纯化的Tat-APE1/ref-1融合蛋白以剂量依赖方式有效转导培养的内皮细胞，并在孵育1小时后达到最大表达。转导的Tat-APE1/ref-1对培养的内皮细胞中TNF-α诱导的单核细胞黏附和血管细胞黏附分子-1表达具有抑制活性。这些结果表明，Tat-APE1/ref-1可能有助于减轻血管内皮细胞活化或血管炎性疾病。
