Effect of 27-hydroxycholesterol on survival and death of human macrophages and vascular smooth muscle cells.
The objective was to compare the effect of a LXR synthetic ligand (T0901317) on cell viability and lysosomal membrane destabilization in human U937 macrophage and aortic smooth muscle cell (HASMC) incubated in the presence of cholesterol or 27-OH and to verify whether the Akt signalling pathway is involved. In U937 macrophages, cholesterol triggered cell survival while 27-OH triggered either survival (low concentration) or a lysosomal independent apoptosis (high concentration). Despite a strong effect of T0901317 on macrophage survival, its effect on cell viability is hampered in cells incubated in the presence of cholesterol or 27-OH. In these cells, cholesterol triggers the phosphorylation of Akt on the Thr308 residue. In HASMC, cholesterol induced apoptosis but no additionnal effect of T0901317 prevented apoptosis. All together, cell survival triggered by LXRs is impaired in the presence of cholesterol or high concentrations of 27-OH in human U937 macrophages and is not effective in HASMC.
Riendeau
Valérie
V
Centre de recherche sur les maladies lipidiques, Centre hospitalier universitaire de Quebec/Centre de recherche du centre hospitalier de l'Universite Laval, Universite Laval, Quebec, QC, Canada.
Garenc
Christophe
C
D017209:Apoptosis / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D006888:Hydroxycholesterols / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D020298:U937 Cells; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D006845:Hydrocarbons, Fluorinated; D006888:Hydroxycholesterols; D051057:Proto-Oncogene Proteins c-akt; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C076996:27-hydroxycholesterol