Kim J.-Y.,Research Institute of Protein Sensor |
Kim J.-Y.,Yeungnam University |
Lee E.-Y.,Research Institute of Protein Sensor |
Lee E.-Y.,Yeungnam University |
And 6 more authors.
Molecules and Cells | Year: 2015
Particulate matter2.5 (PM2.5) is notorious for its strong toxic effects on the cardiovascular, skin, nervous, and reproduction systems. However, the molecular mechanism by which PM2.5 aggravates disease progression is poorly understood, especially in a water-soluble state. In the current study, we investigated the putative physiological effects of aqueous PM2.5 solution on lipoprotein metabolism. Collected PM2.5 from Seoul, Korea was dissolved in water, and the water extract (final 3 and 30 ppm) was treated to human serum lipoproteins, macrophages, and dermal cells. PM2.5 extract resulted in degradation and aggregation of high-density lipoprotein (HDL) as well as low-density lipoprotein (LDL); apoA-I in HDL aggregated and apo-B in LDL disappeared. PM2.5 treatment (final 30 ppm) also induced cellular uptake of oxidized LDL (oxLDL) into macrophages, especially in the presence of fructose (final 50 mM). Uptake of oxLDL along with production of reactive oxygen species was accelerated by PM2.5 solution in a dose-dependent manner. Further, PM2.5 solution caused cellular senescence in human dermal fibroblast cells. Microinjection of PM2.5 solution into zebrafish embryos induced severe mortality accompanied by impairment of skeletal development. In conclusion, water extract of PM2.5 induced oxidative stress as a precursor to cardiovascular toxicity, skin cell senescence, and embryonic toxicity via aggregation and proteolytic degradation of serum lipoproteins. © The Korean Society for Molecular and Cellular Biology. All rights reserved.
Park K.-H.,Yeungnam University |
Cho K.-H.,Yeungnam University |
Cho K.-H.,Research Institute of Protein Sensor
Fish and Shellfish Immunology | Year: 2011
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. © 2011 Elsevier Ltd.