Low-density lipoprotein aggregation is inhibited by apolipoprotein J-derived mimetic peptide D-[113–122]apoJ
Autor: | Jordi Ordóñez-Llanos, Montserrat Pérez-Cuellar, Sandra Villegas, Andrea Rivas-Urbina, José Luis Sánchez-Quesada, Laia Montoliu-Gaya, A. Rull |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Circular dichroism Apolipoprotein B Peptide 030204 cardiovascular system & hematology Mimetic peptides Protein Aggregates 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Humans Molecular Biology Protein secondary structure chemistry.chemical_classification Gel electrophoresis biology Cell Biology Atherosclerosis LDL aggregation Healthy Volunteers Peptide Fragments Sphingomyelins Lipoproteins LDL Clusterin Sphingomyelin Phosphodiesterase 030104 developmental biology chemistry Apolipoprotein J Low-density lipoprotein biology.protein Biophysics lipids (amino acids peptides and proteins) Sphingomyelin D[113-122]apoJ Lipoprotein |
Zdroj: | BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname |
ISSN: | 1388-1981 |
Popis: | Mimetic peptides are promising therapeutic agents for atherosclerosis prevention. A 10-residue class G* peptide from apolipoprotein J (apoJ), namely, D-[113–122]apoJ, possesses anti-inflammatory and anti-atherogenic properties. This prompted us to determine its effect on the aggregation process of low-density lipoprotein (LDL) particles, an early event in the development of atherosclerosis. LDL particles with and without [113–122]apoJ peptide were incubated at 37 °C with sphingomyelinase (SMase) or were left to aggregate spontaneously at room temperature. The aggregation process was analyzed by size-exclusion chromatography (SEC), native gradient gel electrophoresis (GGE), absorbance at 405 nm, dynamic light scattering (DLS), and transmission electronic microscopy (TEM). In addition, circular dichroism was used to determine changes in the secondary structure of apoB, and SDS-PAGE was performed to assess apoB degradation. At an equimolar ratio of [113–122]apoJ peptide to apoB-100, [113–122]apoJ inhibited both SMase-induced or spontaneous LDL aggregation. All methods showed that [113–122]apoJ retarded the progression of SMase-induced LDL aggregation at long incubation times. No effect of [113–122]apoJ on apoB secondary structure was observed. Binding experiments showed that [113–122]apoJ presents low affinity for native LDL but binds readily to LDL during the first stages of aggregation. Laurdan fluorescence experiments showed that mild aggregation of LDL resulted in looser lipid packaging, which was partially prevented by D-[113–122]apoJ. These results demonstrate that [113–122]apoJ peptide prevents SMase-induced LDL aggregation at an equimolar ratio and opens the possibility for the use of this peptide as a therapeutic tool. |
Databáze: | OpenAIRE |
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