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The role of the mitochondria in apoptosis induced by 7β-hydroxycholesterol and cholesterol-5β,6β-epoxide

Published online by Cambridge University Press:  08 March 2007

Lisa Ryan ,
Yvonne C. O'Callaghan  and
Nora M. O'Brien
Lisa Ryan
Affiliation:
Department of Food and Nutritional Sciences, University College Cork, Republic of Ireland
Yvonne C. O'Callaghan
Affiliation:
Department of Food and Nutritional Sciences, University College Cork, Republic of Ireland
Nora M. O'Brien*
Affiliation:
Department of Food and Nutritional Sciences, University College Cork, Republic of Ireland
*
*Corresponding author: Dr Nora M. O'Brien, fax +353 21 4270244, email [email protected]
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Abstract

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Oxysterols are oxygenated derivatives of cholesterol that may be formed endogenously or absorbed from the diet. Significant amounts of oxysterols have frequently been identified in foods of animal origin, in particular highly processed foods. To date, oxysterols have been shown to possess diverse biological activities; however, recent attention has focused on their potential role in the development of atherosclerosis. Oxysterols have been reported to induce apoptosis in cells of the arterial wall, a primary process in the development of atheroma. The aim of the present study was to identify the role of the mitochondria in the apoptotic pathways induced by the oxysterols 7β-hydroxycholesterol (7β-OH) and cholesterol-5β,6β-epoxide (β-epoxide) in U937 cells. To this end, we investigated the effects of these oxysterols on mitochondrial membrane potential, caspase-8 activity, the mitochondrial permeability transition pore and cytochrome c release. 7β-OH-induced apoptosis was associated with a loss in mitochondrial membrane potential after 2 h, accompanied by cytochrome c release from the mitochondria into the cytosol after 16 h. Pre-treatment with a range of inhibitors of the mitochondrial permeability transition pore protected against 7β-OH-induced cell death. In contrast, β-epoxide induced a slight increase in caspase-8 activity but had no effect on mitochondrial membrane potential or cytochrome c release. The present results confirm that 7β-OH-induced apoptosis occurs via the mitochondrial pathway and highlights differences in the apoptotic pathways induced by 7β-OH and β-epoxide in U937 cells.

Keywords

ApoptosisMitochondria7β-HydroxycholesterolCholesterol-5β,6β-epoxideU937 cells
Type
Research Article
Information
British Journal of Nutrition , Volume 94 , Issue 4 , October 2005 , pp. 519 - 525
Copyright
Copyright © The Nutrition Society 2005

References

Ashe, PC & Berry, MD (2003) Apoptotic signalling cascades. Prog Neuro-Psychopharmacol Biol Psych 27, 199–214.CrossRefGoogle Scholar
Bernardi, P, Scorrano, L, Colonna, R, Petronilli, V & Di Lisa, F (1999) Mitochondria and cell death. Eur J Biochem 264, 687–701.CrossRefGoogle ScholarPubMed
Berthier, A, Lemaire-Ewing, S & Prunet, C (2004) Involvement of a calcium-dependent dephosphorylation of BAD associated with the localization of Trpc-1 within lipid rafts in 7-ketocholesterol-induced THP-1 cell apoptosis. Cell Death Differ 8, 897–905.CrossRefGoogle Scholar
Biasi, F, Leonarduzzi, G, Vizio, B, Zanetti, D, Sevanian, A, Sottero, B, Verde, V, Zingaro, B, Chiarpotto, E & Poli, G (2004) Oxysterol mixtures prevent proapoptotic effects of 7-ketocholesterol in macrophages: implications for proatherogenic gene modulation. FASEB J 18, 693–695.CrossRefGoogle ScholarPubMed
Bosinger, SLuf, W & Brandl, E (1993) Oxysterols: their occurrence and biological effects. Int Dairy J 3, 1–33.CrossRefGoogle Scholar
Brown, AJ, Leong, S, Dean, RT & Jessup, W (1997) 7-Hydroperoxycholesterol and its products in oxidised low density lipoprotein and human atherosclerotic plaque. J Lipid Res 38, 1730–1745.CrossRefGoogle ScholarPubMed
Burzik, C, Kaim, G, Dimroth, P, Bamberg, E & Fendler, K (2003) Charge displacements during ATP-hydrolysis and synthesis of the Na + -transporting F 0 F 1 -ATPase of Ilyobacter tartaricus. Biophys J 85, 2044–2054.CrossRefGoogle Scholar
Chen, J, Mehta, JL, Haider, N, Zhang, X, Narula, J & Li, D (2004) Role of caspases in oxLDL-induced apoptotic cascade in human coronary artery endothelial cells. Circ Res 94, 370–376.CrossRefGoogle Scholar
Colles, SM, Maxson, JM, Carlson, SG & Chisolm, GM (2001) Oxidised LDL-induced injury and apoptosis in atherosclerosis. Trends Cardiovasc Med 11, 131–138.CrossRefGoogle ScholarPubMed
Crompton, M (1999) The mitochondrial permeability transition and its role in cell death. Biochem J 341, 233–249.CrossRefGoogle ScholarPubMed
Custodio, JBA, Cardoso, CMP & Almeida, LM (2002) Thiol protecting agents and antioxidants inhibit the mitochondrial permeability transition promoted by etoposide: implications in the prevention of etoposide-induced apoptosis. Chemico-Biolog Interact 140, 169–184.CrossRefGoogle ScholarPubMed
Dubrez, L, Savoy, I, Hamman, A & Solary, E (1996) Pivotal role of a DEVD-sensitive step in etoposide-induced and Fas-mediated apoptotic pathways. EMBO J 15, 5504–5512.CrossRefGoogle ScholarPubMed
Green, D & Kroemer, G (1998) The central executioners of apoptosis: caspases or mitochondria?. Trends Cell Biol 8, 267–271.CrossRefGoogle ScholarPubMed
Halestrap, AP, Clarke, SJ & Javadov, SA (2004) Mitochondrial permeability transition pore opening during myocardial reperfusion – a target for cardioprotection. Cardiovasc Res 61, 372–385.CrossRefGoogle ScholarPubMed
Halestrap, AP, McStay, GP & Clarke, SJ (2002) The permeability transition pore complex: another view. Biochimie 84, 153–166.CrossRefGoogle ScholarPubMed
Hans, G, Malgrange, B & Lallemand, F (2005) β-Carbolines induce apoptosis in cultured cerebellar granule neurons via the mitochondrial pathway. Neuropharmacology 48, 105–117.CrossRefGoogle ScholarPubMed
Kinscherf, R, Claus, R & Wagner, M (1998) Apoptosis caused by oxidised LDL is manganese superoxide dismutase and p53 dependent. FASEB J 12, 461–467.CrossRefGoogle ScholarPubMed
Leonarduzzi, G, Biasi, F, Chiarpotto, EPoli, G (2004) Trojan horse-like behaviour of a biologically representative mixture of oxysterols. Mol Asp Med 25, 155–167.CrossRefGoogle ScholarPubMed
Leonarduzzi, G, Sottero, B & Poli, G (2002) Oxidised products of cholesterol: dietary and metabolic origin, and proatherosclerotic effects (review). J Nutr Biochem 13, 700–710.CrossRefGoogle Scholar
Lizard, G, Miguet, C, Bessede, G, Monier, S, Gueldry, S, Neel, D & Gambert, P (2000) Impairment with various antioxidants of the loss of mitochondrial transmembrane potential and of the cytosolic release of cytochrome c occurring during 7-ketocholesterol-induced apoptosis. Free Radic Biol Med 28, 743–756.CrossRefGoogle ScholarPubMed
Lizard, G, Monier, S, Cordelet, C, Gesquiere, L, Deckert, V, Gueldry, S, Lagrost, L & Gambert, P (1999) Characterization and comparison of the mode of cell death, apoptosis versus necrosis, induced by 7β-hydroxycholesterol and 7-ketocholesterol in the cells of the vascular wall. Arterioscler Thromb Vasc Biol 19, 1190–1200.CrossRefGoogle ScholarPubMed
Martinsson, P, Liminga, G, Nygren, P & Larrson, R (2001) Characteristics of etoposide-induced apoptotic cell death in the U937 human lymphoma cell line. Anticancer Drugs 12 699–705.CrossRefGoogle ScholarPubMed
Maziere, C, Meignottte, A, Dantin, F, Conte, M-AMaziere, J-C & Oxidised, LDL (2000) induces an oxidative stress and activates tumour suppressor p53 in MRC5 human fibroblasts. Biochem Biophys Res Comm 276, 718–723.CrossRefGoogle ScholarPubMed
Miguet, C, Monier, S, Bettiaeb, A, Athias, A, Bessede, O, Laubriet, A, Lemaire, S, Neel, D, Gambert, P & Lizard, G (2001) Ceramide generation occurring during 7β-hydroxycholesterol and 7-ketocholesterol-induced apoptosis is caspase independent and is not required to trigger cell death. Cell Death Differ 8, 83–99.CrossRefGoogle Scholar
Miguet-Alfonsi, C, Prunet, C, Monier, S, Bessede, G, Lemaire-Ewing, S, Berthier, A, Menetrier, F, Neel, D, Gambert, P & Lizard, G (2002) Analysis of oxidative processes and of myelin figures formation before and after the loss of mitochondrial transmembrane potential during 7β-hydroxycholesterol and 7-ketocholesterol-induced apoptosis: comparison with various pro-apoptotic chemicals. Biochem Pharmacol 64, 527–541.CrossRefGoogle ScholarPubMed
Monier, S, Samadi, M & Prunet, C (2003) Impairment of the cytotoxic and oxidative activities of 7β-hydroxycholesterol and 7-ketocholesterol by esterification with oleate. Biochem Biophys Res Comm 303, 814–824.CrossRefGoogle ScholarPubMed
Napoli, C, Quehenberger, O, De Nigris, F, Abete, P, Glass, CK & Palinski, W (2000) Mildly oxidised low density lipoprotein activates multiple apoptotic signalling pathways in human coronary cells. FASEB J 14, 1996–2007.CrossRefGoogle ScholarPubMed
O'Callaghan, YC, Woods, JA & O'Brien, NM (1999) Oxysterol-induced cell death in U937 and HepG2 cells at reduced and normal serum concentrations. Eur J Nutr 38, 255–262.CrossRefGoogle ScholarPubMed
O'Callaghan, YC, Woods, JA & O'Brien, NM (2002) Characteristics of 7β-hydroxycholesterol-induced cell death in a human monocytic blood cell line, U937, and a human hepatoma cell line, HepG2. Toxicol In Vitro 16, 245–251.CrossRefGoogle Scholar
Paniangvait, P, King, AJ, Jones, AD & German, BG (1995) Cholesterol oxides in foods of animal origin. J Food Sci 60, 1159–1174.CrossRefGoogle Scholar
Panini, SR & Sinensky, MS (2001) Mechanisms of oxysterol-induced apoptosis. Curr Opin Lipidol 12, 529–533.CrossRefGoogle ScholarPubMed
Piret, JP, Arnould, T, Fuks, B, Chatelain, P, Remacle, J & Michiels, C (2004) Mitochondria permeability transition-dependent tert -butyl hydroperoxide-induced apoptosis in hepatoma HepG2 cells. Biochem Pharmacol 67, 611–620.CrossRefGoogle ScholarPubMed
Ryan, L, O'Callaghan, YC & O'Brien, NM (2004 a) Generation of an oxidative stress precedes caspase activation during 7β-hydroxycholesterol-induced apoptosis in U937 cells. J Biochem Mol Toxicol 18, 50–59.CrossRefGoogle ScholarPubMed
Ryan, L, O'Callaghan, YC & O'Brien, NM (2004 b) Comparison of the apoptotic processes induced by the oxysterols 7β-hydroxycholesterol and cholesterol-5β,6β-epoxide. Cell Biol Toxicol 20, 313–323.CrossRefGoogle ScholarPubMed
Schroepfer, GJ (2000) Oxysterols: modulators of cholesterol metabolism and other processes. Physiol Rev 80, 361–554.CrossRefGoogle ScholarPubMed
Seye, CI, Knaapen, MWM, Daret, D, Desgranges, C, Herman, AG, Kockx, MM & Bult, H (2004) 7-Ketocholesterol induces reversible cytochrome c release in smooth muscle cells in absence of mitochondrial swelling. Cardiovasc Res 64, 144–153.CrossRefGoogle ScholarPubMed
Smith, PK, Krohn, RI, Hermanson, GT, Mallia, AK, Gartner, FH, Provenzano, MD, Fujimoto, FK, Goeke, NM, Olson, BJ & Klenk, DC (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150, 76–85.CrossRefGoogle ScholarPubMed
Strauss, GHS (1991) Non-random cell killing in cryopreservation: implications for performance of the battery of leukocyte tests (BLT) I. Toxic and immunotoxic effects. Mutat Res 252, 1–15.CrossRefGoogle ScholarPubMed
Uemura, M, Manabe, H, Yoshida, N, Fujita, N, Ochiai, J, Matsumoto, N, Takagi, T, Naito, Y & Yoshikawa, T (2002) α-Tocopherol prevents apoptosis of vascular endothelial cells via a mechanism exceeding that of mere antioxidation. Eur J Pharmacol 456, 29–37.CrossRefGoogle Scholar
Vindis, C, Elbaz, M, Escargueil-Blanc, I, Auge, N, Heniquez, A, Thiers, J-C & Negre-Salvayre, R (2005) Two distinct calcium-dependent mitochondrial pathways are involved in oxidised LDL-induced apoptosis. Arterioscler Thromb Vasc Biol 25, 639–645.CrossRefGoogle ScholarPubMed