Cubbing in proapolipoprotein maturation
| Autor: | Godfrey S. Getz, Catherine A. Reardon |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty Apolipoprotein B Biology Biochemistry Endocrinology Internal medicine polycyclic compounds medicine Animals Secretion Enhancer Proprotein Research Articles Glycoproteins Apolipoprotein A-I Intracellular Signaling Peptides and Proteins nutritional and metabolic diseases Cell Biology Phenotype Procollagen peptidase biology.protein Female lipids (amino acids peptides and proteins) Lipoproteins HDL Function (biology) Homeostasis |
| Zdroj: | Journal of Lipid Research. 52:1861-1864 |
| ISSN: | 0022-2275 |
| Popis: | Given the increased prevalence of cardiovascular disease in the world, the search for genetic variations that impact risk factors associated with the development of this disease continues. Multiple genetic association studies demonstrate that procollagen C-proteinase enhancer 2 (PCPE2) modulates HDL levels. Recent studies revealed an unexpected role for this protein in the proteolytic processing of pro-apolipoprotein (apo) A-I by enhancing the cleavage of the hexapeptide extension present at the N-terminus of apoA-I. To investigate the role of the PCPE2 protein in an in vivo model, PCPE2-deficient (PCPE2 KO) mice were examined, and a detailed characterization of plasma lipid profiles, apoA-I, HDL speciation, and function was done. Results of isoelectric focusing (IEF) electrophoresis together with the identification of the amino terminal peptides DEPQSQWDK and WHVWQQDEPQSQWDVK, representing mature apoA-I and pro-apoA-I, respectively, in serum from PCPE2 KO mice confirmed that PCPE2 has a role in apoA-I maturation. Lipid profiles showed a marked increase in plasma apoA-I and HDL-cholesterol (HDL-C) levels in PCPE2 KO mice compared with wild-type littermates, regardless of gender or diet. Changes in HDL particle size and electrophoretic mobility observed in PCPE2 KO mice suggest that the presence of pro-apoA-I impairs the maturation of HDL. ABCA1-dependent cholesterol efflux is defective in PCPE2 KO mice, suggesting that the functionality of HDL is altered. |
| Databáze: | OpenAIRE |
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