Kyung Hyun Cho
Yeungnam University, South Korea
Posters & Accepted Abstracts: J Diabetes Metab
Glycation of apolipoproteinsis. major feature of production of dysfunctional high-density lipoproteins (HDL), which is associated with incidence of several metabolic diseases such as coronary artery disease and diabetes. High-density lipoprotein (HDL) and apolipoprotein(apo) A-I have strong antioxidant and anti-inflammatory properties in the plasma.. Fructose-induced non-enzymatic glycation of apoA-I can lead to the production ofdysfunctionalapoA-I and HDL. To compare the physiologic effects of dysfunctional apoA-I and HDL, reconstituted HDL containing native apoA-I (nA-I) or glycated apoA-I (gA-I) was injected into zebrafish embryosin the presence of inflammatory molecules. Co-injection of oxidized LDL (oxLDL) and nA-I-rHDLimproved embryo survival, while co-injection of oxLDL and gA-I-rHDL aggravated inflammatory deaths. Using pancreatic β-cells, insulin secretion was impaired by gA-I in the lipid-free and reconstituted HDL (rHDL) states up to 35%, and 40%, respectively, under hyperglycemic conditions (25 mM glucose). Treatment withgA-I and HDL from elderly patients to human umbilical vein endothelial cells (HUVECs) caused 1.8- fold, and 1.5-fold increased cellular senescence, respectively, along with increased lysosomal enlargement. In the lipid-free and rHDL states, gA-I caused 1.5-fold and 2.5-fold higher embryo death, respectively,along with production of oxidized species. Furthermore, rHDL containing gA-I (gA-I-rHDL) showed. higher isoelectric point (pI, approximately 8.5), whereas rHDL-containing nA-I(nAI- rHDL) showed. narrow band range with lower pI (around 8.0) as well as much smaller particlesize than that of nA-I-rHDL. Conclusively, fructose-mediated apoA-I glycation resulted in severe loss of several beneficial functions of apoA-I and HDL, including anti-senescence and insulin secretion activities, accompanied by increased susceptibility of protein degradation and structural modification.
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