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International Journal of Toxicology
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Articles

Involvement of Calcium in 7β-Hydroxycholesterol and Cholesterol-5β,6β-Epoxide-Induced Apoptosis

L. Ryan
Y. C. O’Callaghan
N. M. O’Brien

Department of Food and Nutritional Sciences, University College Cork, Ireland

Correspondence: Address correspondence to Dr. N. M. O’Brien, Nutritional Sciences, Department of Food and Nutritional Sciences, University College Cork, Cork, Ireland. E-mail:nob{at}ucc.ie

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. 7β-Hydroxycholesterol (7β-OH) and cholesterol-5β,6β-epoxide (β-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 intra-cellular 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 7β-OH and β-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 7β-OH whereas nifedipine had a protective effect in both 7β-OH and β-epoxide–treated cells, though these compounds did not restore viability to control levels. Verapamil, nifedipine, and ALLM prevented apoptosis induced by β-epoxide. None of the compounds employed in the current study protected against 7β-OH–induced apoptosis. Our results implicate calcium signaling in the apoptotic pathway induced by β-epoxide and also highlight differences between apoptosis induced by 7β-OH and β-epoxide.

Key Words: Apoptosis • Calcium • Cholesterol-5β • 6β-Epoxide • 7β-Hydroxycholesterol • U937 Cells

International Journal of Toxicology, Vol. 25, No. 1, 35-39 (2006)
DOI: 10.1080/10915810500488387


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S. Lordan, J. J. Mackrill, and N. M. O'Brien
Involvement of Fas Signalling in 7{beta}-Hydroxycholesterol-and Cholesterol-5{beta},6{beta}-Epoxide-Induced Apoptosis
International Journal of Toxicology, May 1, 2008; 27(3): 279 - 285.
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