title: A zebrafish model for the rapid evaluation of pro-oxidative and inflammatory death by lipopolysaccharide, oxidized low-density lipoproteins, and glycated high-density lipoproteins.
abstract: Oxidation and inflammation are leading causes of nearly all chronic metabolic disorders, and play major roles in cardiovascular disease, cancer, and chronic age-dependent disease. 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 of dysfunctional apoA-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 embryos in the presence of inflammatory molecules. Co-injection of reconstituted HDL containing VLDL and LDL gA-I (gA-I-rHDL) and lipopolysaccaride (LPS) resulted in acute embryo deaths, while rHDL containing nA-I (nA-I-rHDL) and LPS resulted in significantly enhanced survival. Co-injection of oxidized LDL (oxLDL) and nA-I-rHDL improved embryo survival, while co-injection of oxLDL and gA-I-rHDL aggravated inflammatory deaths. Furthermore, co-injection of oxLDL and HDL(2) (5 ng of protein) or HDL(3) (15 ng of protein) from the young group (22 ± 2 years old) showed significantly increased embryo survival compared with the same co-injection of HDL from the elderly group (71 ± 4 years old). In conclusion, our assay system provides a rapid and economic method to screen antioxidant and anti-inflammatory agents using zebrafish embryos.
authors: School of Biotechnology, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors: Ki-Hoon
authors: KH
authors: Park
authors: Kyung-Hyun
authors: KH
authors: Cho
mesh_terms: D000367:Age Factors; D000368:Aged; D000818:Animals; D016632:Apolipoprotein A-I / Q000008:administration & dosage / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D001681:Biological Assay / Q000379:methods; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D017127:Glycation End Products, Advanced / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008075:Lipoproteins, HDL / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000008:administration & dosage; D008297:Male; D008845:Microinjections; D017382:Reactive Oxygen Species / Q000378:metabolism; D016019:Survival Analysis; D055815:Young Adult; D015027:Zebrafish
chemical_list: D016632:Apolipoprotein A-I; D017127:Glycation End Products, Advanced; D008070:Lipopolysaccharides; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein