title: Fructated apolipoprotein A-I exacerbates cellular senescence in human umbilical vein endothelial cells accompanied by impaired insulin secretion activity and embryo toxicity.
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 (pI, approximately 8.5), whereas rHDL containing nA-I (nA-I-rHDL) showed a narrow band range with lower pI (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.
authors.affiliation: a Dept. of Medical Biotechnology, Yeungnam University, Gyeongsan, Republic of Korea.|b Research Institute of Protein Sensor, Yeungnam University, Gyeongsan, Republic of Korea.|c BK21plus Program Serum Biomedical Research and Education Team, Yeungnam University, Gyeongsan, Republic of Korea.
authors.forename: Ki-Hoon
authors.initials: KH
authors.lastname: Park
authors.affiliation: a Dept. of Medical Biotechnology, Yeungnam University, Gyeongsan, Republic of Korea.|b Research Institute of Protein Sensor, Yeungnam University, Gyeongsan, Republic of Korea.|c BK21plus Program Serum Biomedical Research and Education Team, Yeungnam University, Gyeongsan, Republic of Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Kim
authors.affiliation: a Dept. of Medical Biotechnology, Yeungnam University, Gyeongsan, Republic of Korea.|b Research Institute of Protein Sensor, Yeungnam University, Gyeongsan, Republic of Korea.|c BK21plus Program Serum Biomedical Research and Education Team, Yeungnam University, Gyeongsan, Republic of Korea.
authors.forename: Inho
authors.initials: I
authors.lastname: Choi
authors.affiliation: d Department of Biochemistry and Molecular Biology, Yeungnam University, College of Medicine, Daegu, Republic of Korea.
authors.forename: Jae-Ryong
authors.initials: JR
authors.lastname: Kim
authors.affiliation: e Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea.
authors.forename: Kyu Chang
authors.initials: KC
authors.lastname: Won
authors.affiliation: a Dept. of Medical Biotechnology, Yeungnam University, Gyeongsan, Republic of Korea.|b Research Institute of Protein Sensor, Yeungnam University, Gyeongsan, Republic of Korea.|c BK21plus Program Serum Biomedical Research and Education Team, Yeungnam University, Gyeongsan, Republic of Korea.
authors.forename: Kyung-Hyun
authors.initials: KH
authors.lastname: Cho
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000494:pharmacology*; D050197:Atherosclerosis / Q000139:chemically induced / Q000503:physiopathology; D016922:Cellular Senescence / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005632:Fructose / Q000737:chemistry / Q000378:metabolism*; D006031:Glycosylation; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008075:Lipoproteins, HDL / Q000378:metabolism*; D055815:Young Adult; D015027:Zebrafish / Q000254:growth & development / Q000378:metabolism
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D007328:Insulin; D008075:Lipoproteins, HDL; D005632:Fructose
keywords: apolipoprotein A-I; apolipoprotéine A-I; cellular senescence; fructation; glycation par le fructose; high-density lipoprotein; insulin secretion; lipoprotéine de haute densité; senescence cellulaire; sécrétion d’insuline