title: Modified apolipoprotein (apo) A-I by artificial sweetener causes severe premature cellular senescence and atherosclerosis with impairment of functional and structural properties of apoA-I in lipid-free and lipid-bound state.
abstract: Long-term consumption of artificial sweeteners (AS) has been the recent focus of safety concerns. However, the potential risk of the AS in cardiovascular disease and lipoprotein metabolism has not been investigated sufficiently. We compared the influence of AS (aspartame, acesulfame K, and saccharin) and fructose in terms of functional and structural correlations of apolipoprotein (apo) A-I and high-density lipoproteins (HDL), which have atheroprotective effects. Long-term treatment of apoA-I with the sweetener at physiological concentration (3 mM for 168 h) resulted in loss of antioxidant and phospholipid binding activities with modification of secondary structure. The AS treated apoA-I exhibited proteolytic cleavage to produce 26 kDa-fragment. They showed pro-atherogenic properties in acetylated LDL phagocytosis of macrophages. Each sweetener alone or sweetener-treated apoA-I caused accelerated senescence in human dermal fibroblasts. These results suggest that long-term consumption of AS might accelerate atherosclerosis and senescence via impairment of function and structure of apoA-I and HDL.
authors.affiliation: School of Biotechnology, Yeungnam University, Gyeongsan 712-749, Korea.
authors.forename: Wookju
authors.initials: W
authors.lastname: Jang
authors.forename: Nam Ho
authors.initials: NH
authors.lastname: Jeoung
authors.forename: Kyung-Hyun
authors.initials: KH
authors.lastname: Cho
mesh_terms: D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism*; D050197:Atherosclerosis / Q000139:chemically induced / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005632:Fructose / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D013549:Sweetening Agents / Q000009:adverse effects* / Q000737:chemistry
chemical_list: D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D013549:Sweetening Agents; D005632:Fructose