Fructated apolipoprotein A-I showed severe structural modification and loss of beneficial functions in lipid-free and lipid-bound state with acceleration of atherosclerosis and senescence.
Non-enzymatic glycation of serum apolipoproteins is a main feature of diabetes mellitus under hyperglycemia. Advanced glycation end products are implicated in the development of aging and metabolic syndrome, including premature atherosclerosis in diabetic subjects. ApoA-I is the principal protein constituent of HDL. In this study, glycated human apoA-I (gA-I) by fructation was characterized on functional and structural correlations in lipid-free and lipid-bound states. The gA-I showed more spontaneous multimeric band formation up to pentamer and exhibited slower elution profile with more degraded fragments from fast protein liquid chromatography. The gA-I showed modified secondary structure from fluorescence and circular dichroism analysis. Reconstituted high-density lipoprotein (rHDL) containing the gA-I had less content of phospholipid with a much smaller particle size than those of rHDL-containing nA-I (nA-I-rHDL). The rHDL containing gA-I (gA-I-rHDL) consisted of less molecular number of apoA-I than nA-I-rHDL with decreased alpha-helical content. Treatment of the gA-I-rHDL induced more atherogenic process in macrophage cell and premature senescence in human dermal fibroblast cell. Conclusively, fructose-mediated apoA-I glycation resulted in severe loss of several beneficial functions of apoA-I and HDL regarding anti-senescence and anti-atherosclerosis activities due to a lack of anti-oxidant activity with increased susceptibility of protein degradation and structural modification.
Park
Ki-Hoon
KH
Aging-associated Vascular Disease Research Center, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
Jang
Wookju
W
Kim
Ki-Yong
KY
Kim
Jae-Ryong
JR
Cho
Kyung-Hyun
KH
D000375:Aging / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D050197:Atherosclerosis / Q000378:metabolism*; D016922:Cellular Senescence; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005632:Fructose / Q000737:chemistry / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D017433:Protein Structure, Secondary
D016632:Apolipoprotein A-I; D017127:Glycation End Products, Advanced; D008075:Lipoproteins, HDL; D005632:Fructose