Involvement of calcium in 7beta -hydroxycholesterol and cholesterol-5beta,6beta -epoxide-induced apoptosis.
Oxidized low-density lipoprotein (oxLDL) is believed to play a central role in the development of atherosclerosis. The induction of apoptosis in cells of the arterial wall is a critical event in the development of atheroma. 7beta-Hydroxycholesterol (7beta-OH) and cholesterol-5beta,6beta-epoxide (beta-epoxide) are components of oxLDL and have previously been shown to be potent inducers of apoptosis. The exact mechanism through which these oxysterols induce apoptosis remains to be fully elucidated. A perturbation of intracellular calcium homeostasis has been found to trigger apoptosis in many experimental systems. The aim of the present study was to determine the involvement of calcium signaling in 7beta-OH and beta-epoxide-induced apoptosis. To this end, the authors employed the calcium channel blockers verapamil and nifedipine and inhibitors of calpain activation, ALLM and ALLN. Verapamil protected against the decrease in viability induced by 7beta-OH whereas nifedipine had a protective effect in both 7beta-OH and beta-epoxide-treated cells, though these compounds did not restore viability to control levels. Verapamil, nifedipine, and ALLM prevented apoptosis induced by beta-epoxide. None of the compounds employed in the current study protected against 7beta-OH-induced apoptosis. Our results implicate calcium signaling in the apoptotic pathway induced by beta-epoxide and also highlight differences between apoptosis induced by 7beta-OH and beta-epoxide.
Ryan
L
L
Department of Food and Nutritional Sciences, University College Cork, Ireland.
O'Callaghan
Y C
YC
O'Brien
N M
NM
D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004336:Drug Antagonism; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D007976:Leupeptins / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009543:Nifedipine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D020298:U937 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D006888:Hydroxycholesterols; D007976:Leupeptins; D009842:Oligopeptides; C063261:acetylleucyl-leucyl-norleucinal; C069861:calpain inhibitor 2; C002415:cholesterol alpha-oxide; C011724:cholest-5-en-3 beta,7 alpha-diol; D002784:Cholesterol; D014700:Verapamil; D009543:Nifedipine; D002118:Calcium