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- Title
Fructated apolipoprotein A-I exacerbates cellular senescence in human umbilical vein endothelial cells accompanied by impaired insulin secretion activity and embryo toxicity.
- Authors
Park, Ki-Hoon; Kim, Jae-Yong; Choi, Inho; Kim, Jae-Ryong; Won, Kyu Chang; Cho, Kyung-Hyun
- Abstract
Glycation of apolipoproteins is a major feature of the production of dysfunctional high-density lipoprotein (HDL), which is associated with the incidence of several metabolic diseases such as coronary artery disease and diabetes. In this report, fructated apoA-I (fA-I) induced by fructose treatment showed a covalently multimerized band without cross-linking, and lysine residues were irreversibly modified to prevent crosslinking. Using pancreatic β-cells, insulin secretion was impaired by fA-I in the lipid-free and reconstituted HDL (rHDL) states, by up to 35%, and 40%, respectively, under hyperglycemic conditions (25 mmol/L glucose). Treatment of human umbilical vein endothelial cells (HUVECs) with fA-I and HDL from elderly patients caused a 1.8-fold and 1.5-fold increased cellular senescence, respectively, along with increased lysosomal enlargement. In the lipid-free and rHDL states, fA-I increased embryo death by 1.5-fold and 2.5-fold, respectively, along with the production of oxidized species. Furthermore, rHDL containing fA-I (fA-I-rHDL) showed a higher isoelectric point (p I, approximately 8.5), whereas rHDL containing nA-I (nA-I-rHDL) showed a narrow band range with lower p I (around 8.0) as well as a much smaller particle size than that of nA-I-rHDL. In conclusion, fructose-mediated apoA-I fructation resulted in the severe loss of several beneficial functions of apoA-I and HDL, including anti-senescence and insulin secretion activities, accompanied with increased susceptibility to protein degradation and structural modification.
- Subjects
APOLIPOPROTEINS; HIGH-density lipoprotein receptors; PANCREATIC beta cells; ENDOTHELIAL cells; GLUCAGON
- Publication
Biochemistry & Cell Biology, 2016, Vol 94, Issue 4, p337
- ISSN
0829-8211
- Publication type
Article
- DOI
10.1139/bcb-2015-0165