[BIO Colloquium] Functional regulation of APE1/Ref-1 in Vascular Inflammation
  • Byeong Hwa Jeon, Ph.D. (Chungnam National University)
  • SLS Colloquia / Apr 22th 04:00 pm / AMRB 113
Abstract
 

Apurinic apyrimidinic endonuclease 1/Redox factor-1 (APE1/Ref-1) has a pleiotropic role in controlling cellular response to oxidative stress. APE1/Ref-1 is involved both in the base excision repair of abasic DNA lesions and in eukaryotic transcriptional regulation including AP-1, NF-kB etc. APE1/Ref-1 is localized in the nucleus, but growing evidence indicates that APE1/Ref-1 can be also localized in cytoplasm, especially during high metabolic or proliferative states. This trafficking of APE1/Ref-1 between cellular compartments is reflected the several involvement to different types of stressors. Post-translational protein modification is a crucial mechanism of regulating protein function in eukaryotic cells. Several kinds of post-translational modification of APE1/Ref-1 such as acetylation have been observed suggesting involved in cell survival, adaptation and proliferation processes. APE1/Ref-1 is essential for cellular survival and embryonic lethal in knockout mouse models. APE1/Ref-1(+/?) mice showed impaired endothelium-dependent vasorelaxation, reduced vascular NO levels, and are hypertensive. APE1/Ref-1 reduces intracellular reactive oxygen species production by negatively regulating the activity of the NADPH oxidase. Overexpression of APE1/Ref-1 suppresses monocyte adhesion to endothelial cells and inhibits hypoxia?induced endothelial cell apoptosis. Moreover, APE1/Ref-1 inhibits balloon injury-induced neointimal formation in rats. Recently, it was reported that APE1/Ref-1 suppressed oxidized LDL- or protein kinase C-induced p66shc phosphorylation in endothelial cells. Here I will introduce diverse functions of APE1/Ref-1 against vascular inflammation.

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