Estradiol enhances the resistance of LDL to oxidation by stabilizing apoB-100 conformation.
Among different proposed mechanisms to account for the protection exerted by estrogens against cardiovascular diseases, the antioxidant effect has attracted considerable attention. We confirmed that 17-beta-estradiol (E2), when added to human LDL at a 6:1 ratio to apoB-100, markedly delays the phase of massive LDL lipid peroxidation induced by Cu(2+). We also observed an increased oxidative resistance of E2-treated LDL by monitoring the early phase of oxidative degradation on the basis of increased LDL surface polarity by the generalized polarization of the lipophilic fluorescent probe 2-(dimethylamino)-6-lauroylnaphthalene (Laurdan). A scavenging of free radicals by E2 is ruled out since, consistent with its structure, its rate constant for the reduction of peroxy radicals is extremely low, i.e., 0.02% of that of vitamin E. Tryptophan fluorescence lifetime and circular dichroism measurements revealed that (i) apoB-100 undergoes a conformational modification and a progressive loss of secondary structure during lipid peroxidation; (ii) E2 increases apoB-100 secondary structure and modifies its conformation; and (iii) the apoB-100 conformational change induced by E2 makes this protein resistant to modifications brought about by lipid peroxidation. We propose that E2, by affecting apoB-100 secondary structure and conformation, modifies the interaction of this protein with the outer layer of the LDL particle thus increasing its overall oxidative resistance.
Brunelli
R
R
I and II Clinica Ostetrica e Ginecologica, Universitá di Roma La Sapienza, Viale del Policlinico 155, 00185 Roma, Italy.
Mei
G
G
Krasnowska
E K
EK
Pierucci
F
F
Zichella
L
L
Ursini
F
F
Parasassi
T
T
D015081:2-Naphthylamine / Q000031:analogs & derivatives* / Q000737:chemistry; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000737:chemistry* / Q000378:metabolism; D002942:Circular Dichroism; D004958:Estradiol / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D005454:Fluorescence Polarization; D005456:Fluorescent Dyes / Q000737:chemistry; D016166:Free Radical Scavengers / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007848:Laurates / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence; D014364:Tryptophan / Q000737:chemistry
D000975:Antioxidants; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers; D007848:Laurates; D008077:Lipoproteins, LDL; D004958:Estradiol; D014364:Tryptophan; D015081:2-Naphthylamine; C065580:laurdan