【論文摘要】Short-term Shear Flow Increases the Posttranslational Acetylome in Endothelial Cells

Bin Huang ； Wen-Kuo Hsieh ； Ling Wang

《海峽循環醫學雜誌》 1卷2S期 (2019/09) Pp. 15-15

https://doi.org/10.6907/SCJ.201909/SP_1(2).0013

摘要

Background/Synopsis: Protein acetylation/deacetylation, named acetylome, are important processes in the regulation of signaling cascades and involved in mediating cellular responses to environmental changes. Sustained blood shear flow can regulate protein acetylome and is well known to promote endothelial homeostasis. However, an early acetylome regulated by short-term shear flow remains unclear. Objectives/Purpose: The present study is to establish a whole picture of acetylomes obtained from short-term to sustained shear flow so that the correspondent physiological responses and endothelium homeostasis can be understood. Methods/Results: Endothelial cells (ECs) derived from the human umbilical cord vein were exposed to laminar shear flow of 12 dyne/cm2 for 1 hour were subjected to iTRAQ-labeled shotgun proteomic analysis to characterize the acetylome and the acetylated lysine residues. The acetylome of ECs treated with the resveratrol (RVT) for 1 hr was analyzed and used as a reference. There were 628 proteins with increased acetylation and 22 proteins with decreased acetylation identified under ephemeral shear flow (1 hr). ECs treated RVT enhanced the acetylation of 145 proteins and reduced the acetylation of 23 proteins. There were 129 acetylated proteins and 2 deacetylated proteins consistently detected under both shear flow and RVT treatments. Ingenuity pathway analysis (IPA) showed that these proteins were involved in heat shock response. Co-immunoprecipitation (Co-IP) analysis with anti-acetyl antibody revealed an elevated acetylation of mitochondrial HSP60 (HSPD1) and mitochondrial citrate synthase. Conclusion: Short-term shear flow increases and decreases the acetylation of some proteins similar to RVT treatment. Those acetylome changes (including HSP60 and citrate synthase) reflect the endothelial responses to short-term shear flow. The alteration of acetylation relating to protein activities or functional changes remain to be clarified. The acetylome of ECs under sustained physiological shear flow needs to be further studied.