Seeking for a modified lipoprotein present in plasma that could account for the atherogenic effect of high cholesterol, several years ago electronegative LDL(-) was identified. The peculiar feature of LDL(-) is an apoprotein misfolding that triggers the formation of aggregates, perfectly fitting in size the subendothelial droplets observed in early phases of atherogenesis. Apoprotein misfolding was therefore proposed as a possible atherogenic modification. LDL(-) can be spontaneously produced in vitro by plasma incubation through phospholipid hydrolysis catalyzed by the activity of endogenous phospholipases. As a consequence, apoprotein is misfolded. 17beta-Estradiol (E2), a specific ligand to apoB-100, was used to unravel the relationship between negative charge of the lipoprotein and apoprotein structural/conformational shift. Although E2 addition to plasma does not prevent LDL(-) generation nor phospholipase activity, it deeply stabilizes apoB-100 structure, thus preventing its structural and conformational shift. Apoprotein stabilization extends to lipids. Indeed, while a loosening of lipid packing is observed together with apoprotein misfolding, conversely, when E2 stabilizes apoprotein, lipid structure is preserved. Finally, even in the presence of LDL(-), the E2-stabilized LDL is resistant to aggregation, unambiguously demonstrating that misfolding, but not negative charge, primes aggregation. In conclusion, electronegative charge and misfolding are independent and distinct features of LDL(-), and apoprotein misfolding rather than the increase in the negative charge emerges both as a valid biomarker and as an appealing pharmacological and nutritional target.
Brunelli, R., Balogh, G., Costa, G., De Spirito, M., Greco, G., Mei, G., et al. (2010). Estradiol binding prevents ApoB-100 misfolding in electronegative LDL(-). BIOCHEMISTRY, 7297-7302.
|Tipologia:||Articolo su rivista|
|Citazione:||Brunelli, R., Balogh, G., Costa, G., De Spirito, M., Greco, G., Mei, G., et al. (2010). Estradiol binding prevents ApoB-100 misfolding in electronegative LDL(-). BIOCHEMISTRY, 7297-7302.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore BIO/10|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1021/bi100715f|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2010|
|Titolo:||Estradiol binding prevents ApoB-100 misfolding in electronegative LDL(-).|
|Autori:||Brunelli, R; Balogh, G; Costa, G; De Spirito, M; Greco, G; Mei, G; Nicolai, E; Vigh, L; Ursini, F; Parasassi, T;|
|Appare nelle tipologie:||01 - Articolo su rivista|