TY - JOUR
T1 - Oxysterols from oxidized LDL are cytotoxic but fail to induce hsp70 expression in endothelial cells
AU - Pirillo, Angela
AU - Zhu, Weimin
AU - Roma, Paola
AU - Galli, Giovanni
AU - Caruso, Donatella
AU - Pellegatta, Fabio
AU - Catapano, Alberico L.
PY - 1999/11/26
Y1 - 1999/11/26
N2 - Oxidized low density lipoprotein (OxLDL) possesses several proatherogenic characteristics, among which a marked cytotoxicity. In vitro, cytotoxicity of OxLDL to endothelial cells is associated with an increase in the expression of the inducible form of heat shock protein 70 (hsp70), generally regarded as a cytoprotective protein. Oxidized derivatives of cholesterol which form upon LDL oxidation are cytotoxic. Moreover, most of the OxLDL cytotoxicity is due to its lipid moiety, in particular to oxysterols. In this report we demonstrate that although oxysterols identified in OxLDL are cytotoxic, they cannot trigger the increase in hsp70 expression observed with intact oxidized lipoproteins. We speculate therefore that oxysterols may represent the most toxic form of oxidized lipids in LDL because they cannot activate a rescue mechanism (i.e. the hsp response) and may contribute significantly to cell death within atherosclerotic plaques.
AB - Oxidized low density lipoprotein (OxLDL) possesses several proatherogenic characteristics, among which a marked cytotoxicity. In vitro, cytotoxicity of OxLDL to endothelial cells is associated with an increase in the expression of the inducible form of heat shock protein 70 (hsp70), generally regarded as a cytoprotective protein. Oxidized derivatives of cholesterol which form upon LDL oxidation are cytotoxic. Moreover, most of the OxLDL cytotoxicity is due to its lipid moiety, in particular to oxysterols. In this report we demonstrate that although oxysterols identified in OxLDL are cytotoxic, they cannot trigger the increase in hsp70 expression observed with intact oxidized lipoproteins. We speculate therefore that oxysterols may represent the most toxic form of oxidized lipids in LDL because they cannot activate a rescue mechanism (i.e. the hsp response) and may contribute significantly to cell death within atherosclerotic plaques.
KW - 25-Hydroxycholesterol
KW - 5,6-Epoxycholesterol
KW - 7- Ketocholesterol
KW - 7-Hydroperoxycholesterol
KW - 7-Hydroxycholesterol
KW - Stress protein
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U2 - 10.1016/S0014-5793(99)01497-0
DO - 10.1016/S0014-5793(99)01497-0
M3 - Article
C2 - 10580102
AN - SCOPUS:0032754476
VL - 462
SP - 113
EP - 116
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 1-2
ER -