Apoptosis

, Volume 11, Issue 10, pp 1661–1675

Bcl-2 protein family: Implications in vascular apoptosis and atherosclerosis

Review

Abstract

Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic and proliferative responses of vascular cells during progression of the atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic and intrinsic apoptosis signalling pathways and more recently it has become evident that they mediate the apoptotic response of vascular cells in response to oxidation and inflammation either in a provocative or an inhibitory mode of action. Here we address Bcl-2 proteins as major therapeutic targets for the treatment of atherosclerosis and underscore the need for the novel preventive and therapeutic interventions against atherosclerosis, which should be designed in the light of molecular mechanisms regulating apoptosis of vascular cells in atherosclerotic lesions.

Keywords

Apoptosis Atherosclerosis Bcl-2 Oxidation Inflammation 

Abbreviations

Bcl-2

B cell leukemia/lymphoma-2

Caspases

cysteinyl-directed aspartate-specific proteases

Endo G

endonuclease G

TRADD

TNFR-associated death domain protein

FADD

Fas-associated death domain protein

Daxx

death-associated protein 6

RIP

receptor interacting protein

RAIDD

RIP-associated Protein with a Death Domain

FLIP

FLICE inhibitory protein

cIAP

cellular inhibitor of apoptosis protein-1

SMC

smooth muscle cell

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Littlewood TD, Bennett MR (2003) Apoptotic cell death in atherosclerosis. Curr Opin Lipidol 14:469–475PubMedGoogle Scholar
  2. 2.
    Morissette MR, Rosenzweig A (2005) Targeting survival signaling in heart failure. Curr Opin Pharmacol 5:165–170PubMedGoogle Scholar
  3. 3.
    Hajra KM, Liu JR (2004) Apoptosome dysfunction in human cancer. Apoptosis 9:691–704PubMedGoogle Scholar
  4. 4.
    Donath MY, Halban PA (2004) Decreased beta-cell mass in diabetes: significance, mechanisms and therapeutic implications. Diabetologia 47:581–589PubMedGoogle Scholar
  5. 5.
    Dickson DW (2004) Apoptotic mechanisms in Alzheimer neurofibrillary degeneration: cause or effect? J Clin Invest 2004; 114:23–27PubMedGoogle Scholar
  6. 6.
    Heiser D, Labi V, Erlacher M, Villunger A. The Bcl-2 protein family and its role in the development of neoplastic disease. Exp Gerontol 39:1125–1135PubMedGoogle Scholar
  7. 7.
    Korsmeyer SJ (1999) BCL-2 gene family and the regulation of programmed cell death. Cancer Res 59:1693s–1700sPubMedGoogle Scholar
  8. 8.
    Bakhshi A, Wright JJ, Graninger W, et al (1987) Mechanism of the t(14;18) chromosomal translocation: structural analysis of both derivative 14 and 18 reciprocal partners. Proc Natl Acad Sci USA 84:2396–2400PubMedGoogle Scholar
  9. 9.
    Ottilie S, Diaz JL, Horne W, et al (1997) Dimerization properties of human BAD. Identification of a BH-3 domain and analysis of its binding to mutant BCL-2 and BCL-XL proteins. J Biol Chem 272:30866–30872PubMedGoogle Scholar
  10. 10.
    Hsu SY, Kaipia A, McGee E, et al (1997) Bok is a pro-apoptotic Bcl-2 protein with restricted expression in reproductive tissues and heterodimerizes with selective anti-apoptotic Bcl-2 family members. Proc Natl Acad Sci USA 94:12401–12406PubMedGoogle Scholar
  11. 11.
    Rashmi R, Kumar S, Karunagaran D (2005) Human colon cancer cells lacking Bax resist curcumin-induced apoptosis and Bax requirement is dispensable with ectopic expression of Smac or downregulation of Bcl-XL. Carcinogenesis 26:713–723PubMedGoogle Scholar
  12. 12.
    Shibue T, Takeda K, Oda E, et al (2003) Integral role of Noxa in p53-mediated apoptotic response. Genes Dev 17:2233–2238PubMedGoogle Scholar
  13. 13.
    Wang K, Yin XM, Chao DT, et al (1996) BID: a novel BH3 domain-only death agonist. Genes Dev 10:2859–2869PubMedGoogle Scholar
  14. 14.
    Strasser A, O’Connor L, Dixit VM (2000) Apoptosis signaling. Annu Rev Biochem 69:217–245PubMedGoogle Scholar
  15. 15.
    Lee T, Chau L (2001) Fas/Fas ligand-mediated death pathway is involved in oxLDL-induced apoptosis in vascular smooth muscle cells. Am J Physiol Cell Physiol 280:C709–C718PubMedGoogle Scholar
  16. 16.
    Vicca S, Massy ZA, Hennequin C, et al (2003) Apoptotic pathways involved in U937 cells exposed to LDL oxidized by hypochlorous acid. Free Radic Biol Med 35:603–615PubMedGoogle Scholar
  17. 17.
    Norata GD, Tonti L, Roma P, Catapano AL (2002) Apoptosis and proliferation of endothelial cells in early atherosclerotic lesions: possible role of oxidised LDL. Nutr Metab Cardiovasc Dis 12:297–305PubMedGoogle Scholar
  18. 18.
    Reed JC (2000) Mechanisms of apoptosis. Am J Pathol 157:1415–1430PubMedGoogle Scholar
  19. 19.
    Borner C (2003) The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions. Mol Immunol 39:615–647PubMedGoogle Scholar
  20. 20.
    Ashkenazi A, Dixit VM (1998) Death receptors: signaling and modulation. Science 281:1305–1308PubMedGoogle Scholar
  21. 21.
    Sun XM, MacFarlane M, Zhuang J, et al (1999) Distinct caspase cascades are initiated in receptor-mediated and chemical-induced apoptosis. J Biol Chem 274:5053–5060PubMedGoogle Scholar
  22. 22.
    Sprick MR, Weigand MA, Rieser E, et al (2000) FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2. Immunity 12:599–609PubMedGoogle Scholar
  23. 23.
    Bodmer JL, Holler N, Reynard S, et al (2000) TRAIL receptor-2 signals apoptosis through FADD and caspase-8. Nat Cell Biol 2:241–243PubMedGoogle Scholar
  24. 24.
    Soderstrom TS, Poukkula M, Holmstrom TH, et al (2002) Mitogen-activated protein kinase/extracellular signal-regulated kinase signaling in activated T cells abrogates TRAIL-induced apoptosis upstream of the mitochondrial amplification loop and caspase-8. J Immunol 169:2851–2860PubMedGoogle Scholar
  25. 25.
    Scaffidi C, Fulda S, Srinivasan A, et al (1998) Two CD95 (APO-1/Fas) signaling pathways. EMBO J 17:1675–1687PubMedGoogle Scholar
  26. 26.
    Ochs K, Kaina B (2000) Apoptosis induced by DNA damage O6-methylguanine is Bcl-2 and caspase-9/3 regulated and Fas/caspase-8 independent. Cancer Res 60:5815–5824PubMedGoogle Scholar
  27. 27.
    Slee EA, Keogh SA, Martin SJ (2000) Cleavage of BID during cytotoxic drug and UV radiation-induced apoptosis occurs downstream of the point of Bcl-2 action and is catalysed by caspase-3: a potential feedback loop for amplification of apoptosis-associated mitochondrial cytochromecrelease. Cell Death Differ 7:556–565PubMedGoogle Scholar
  28. 28.
    de Moissac D, Gurevich RM, Zheng H, et al (2000) Caspase activation and mitochondrial cytochromecrelease during hypoxia-mediated apoptosis of adult ventricular myocytes. J Mol Cell Cardiol 32:53–63PubMedGoogle Scholar
  29. 29.
    Neame SJ, Rubin LL, Philpott KL (1998) Blocking cytochromecactivity within intact neurons inhibits apoptosis. J Cell Biol 142:1583–1593PubMedGoogle Scholar
  30. 30.
    Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD (1997) The release of cytochromecfrom mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 275:1132–1136PubMedGoogle Scholar
  31. 31.
    Adrain C, Creagh EM, Martin SJ (2001) Apoptosis-associated release of Smac/DIABLO from mitochondria requires active caspases and is blocked by Bcl-2. EMBO J 20:6627–6636PubMedGoogle Scholar
  32. 32.
    van Loo G, van Gurp M, Depuydt B, et al (2002) The serine protease Omi/HtrA2 is released from mitochondria during apoptosis. Omi interacts with caspase-inhibitor XIAP and induces enhanced caspase activity. Cell Death Differ 9:20–26PubMedGoogle Scholar
  33. 33.
    van Loo G, Saelens X, van Gurp M, et al (2002) The role of mitochondrial factors in apoptosis: a Russian roulette with more than one bullet. Cell Death Differ 9:1031–1042PubMedGoogle Scholar
  34. 34.
    Zhang W, Li D, Mehta JL (2004) Role of AIF in human coronary artery endothelial cell apoptosis. Am J Physiol Heart Circ Physiol 286:H354–H358PubMedGoogle Scholar
  35. 35.
    Sakurai K, Katoh M, Fujimoto Y (2001) Alloxan-induced mitochondrial permeability transition triggered by calcium, thiol oxidation, and matrix ATP. J Biol Chem 276:26942–26946PubMedGoogle Scholar
  36. 36.
    Gottlieb RA (2000) Mitochondria: execution central. FEBS Lett 482:6–12PubMedGoogle Scholar
  37. 37.
    Petronilli V, Miotto G, Canton M, et al (1999) Transient and long-lasting openings of the mitochondrial permeability transition pore can be monitored directly in intact cells by changes in mitochondrial calcein fluorescence. Biophys J 76:725–734PubMedCrossRefGoogle Scholar
  38. 38.
    Petronilli V, Penzo D, Scorrano L, et al (2001) The mitochondrial permeability transition, release of cytochromecand cell death. Correlation with the duration of pore openings in situ. J Biol Chem 276:12030–12034PubMedGoogle Scholar
  39. 39.
    Marzo I, Brenner C, Zamzami N, et al (1998) The permeability transition pore complex: a target for apoptosis regulation by caspases and bcl-2-related proteins. J Exp Med 187:1261–1271PubMedGoogle Scholar
  40. 40.
    Shimizu S, Narita M, Tsujimoto Y (1999) Bcl-2 family proteins regulate the release of apoptogenic cytochromecby the mitochondrial channel VDAC. Nature 399:483–487PubMedGoogle Scholar
  41. 41.
    Marzo I, Brenner C, Zamzami N, et al (1998) Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis. Science 281:2027–2031PubMedGoogle Scholar
  42. 42.
    Belzacq AS, Vieira HL, Verrier F, et al (2003) Bcl-2 and Bax modulate adenine nucleotide translocase activity. Cancer Res 63:541–546PubMedGoogle Scholar
  43. 43.
    Finucane DM, Bossy-Wetzel E, Waterhouse NJ, et al (1999) Bax-induced caspase activation and apoptosis via cytochromecrelease from mitochondria is inhibitable by Bcl-xL. J Biol Chem 274:2225–2233PubMedGoogle Scholar
  44. 44.
    Narita M, Shimizu S, Ito T, et al (1998) Bax interacts with the permeability transition pore to induce permeability transition and cytochromecrelease in isolated mitochondria. Proc Natl Acad Sci USA 95:14681–14686PubMedGoogle Scholar
  45. 45.
    Antonsson B, Montessuit S, Sanchez B, Martinou JC (2001) Bax is present as a high molecular weight oligomer/complex in the mitochondrial membrane of apoptotic cells. J Biol Chem 276:11615–11623PubMedGoogle Scholar
  46. 46.
    Nouraini S, Six E, Matsuyama S, et al (2000) The putative pore-forming domain of Bax regulates mitochondrial localization and interaction with Bcl-X(L). Mol Cell Biol 20:1604–1615PubMedGoogle Scholar
  47. 47.
    Mikhailov V, Mikhailova M, Degenhardt K, et al (2003) Association of Bax and Bak homo-oligomers in mitochondria. Bax requirement for Bak reorganization and cytochromecrelease. J Biol Chem 278:5367–5376PubMedGoogle Scholar
  48. 48.
    Mikhailov V, Mikhailova M, Pulkrabek DJ, et al (2001) Bcl-2 prevents Bax oligomerization in the mitochondrial outer membrane. J Biol Chem 276:18361–18374PubMedGoogle Scholar
  49. 49.
    Schendel SL, Xie Z, Montal MO, et al (1997) Channel formation by antiapoptotic protein Bcl-2. Proc Natl Acad Sci USA 94:5113–5118PubMedGoogle Scholar
  50. 50.
    Nechushtan A, Smith CL, Hsu YT, Youle RJ (1999) Conformation of the Bax C-terminus regulates subcellular location and cell death. EMBO J 18:2330–2341PubMedGoogle Scholar
  51. 51.
    Schinzel A, Kaufmann T, Bornerc(2004) Bcl-2 family members: integrators of survival and death signals in physiology and pathology. Biochim Biophys Acta 1644:95–105PubMedGoogle Scholar
  52. 52.
    Nguyen M, Millar DG, Yong VW, et al (1993) Targeting of Bcl-2 to the mitochondrial outer membrane by a COOH-terminal signal anchor sequence. J Biol Chem 268:25265–25268PubMedGoogle Scholar
  53. 53.
    del Mar Martinez-Senac M, Corbalan-Garcia S, Gomez-Fernandez JC (2000) Study of the secondary structure of the C-terminal domain of the antiapoptotic protein bcl-2 and its interaction with model membranes. Biochemistry 39:7744–7752PubMedGoogle Scholar
  54. 54.
    Aritomi M, Kunishima N, Inohara N, et al (1997) Crystal structure of rat Bcl-xL. Implications for the function of the Bcl-2 protein family. J Biol Chem 272:27886–27892PubMedGoogle Scholar
  55. 55.
    Muchmore SW, Sattler M, Liang H, et al (1996) X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature 381:335–341PubMedGoogle Scholar
  56. 56.
    Huang Q, Petros AM, Virgin HW, et al (2002) Solution structure of a Bcl-2 homolog from Kaposi sarcoma virus. Proc Natl Acad Sci USA 99:3428–3433PubMedGoogle Scholar
  57. 57.
    Sattler M, Liang H, Nettesheim D, et al (1997) Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis. Science 275:983–986PubMedGoogle Scholar
  58. 58.
    Korsmeyer SJ, Gross A, Harada H, et al (1999) Death and survival signals determine active/inactive conformations of pro-apoptotic BAX, BAD, and BID molecules. Cold Spring Harb Symp Quant Biol 64:343–350PubMedGoogle Scholar
  59. 59.
    Gilmore AP, Metcalfe AD, Romer LH, Streuli CH (2000) Integrin-mediated survival signals regulate the apoptotic function of Bax through its conformation and subcellular localization. J Cell Biol 149:431–446PubMedGoogle Scholar
  60. 60.
    Desagher S, Osen-Sand A, Nichols A, et al (1999) Bid-induced conformational change of Bax is responsible for mitochondrial cytochromecrelease during apoptosis. J Cell Biol 144:891–901PubMedGoogle Scholar
  61. 61.
    He H, Lam M, McCormick TS, Distelhorst CW (1997) Maintenance of calcium homeostasis in the endoplasmic reticulum by Bcl-2. J Cell Biol 138:1219–1228PubMedGoogle Scholar
  62. 62.
    Bruce-Keller AJ, Begley JG, Fu W, et al (1998) Bcl-2 protects isolated plasma and mitochondrial membranes against lipid peroxidation induced by hydrogen peroxide and amyloid beta-peptide. J Neurochem 70:31–39PubMedCrossRefGoogle Scholar
  63. 63.
    Bogdanov MB, Ferrante RJ, Mueller G, et al (1999) Oxidative stress is attenuated in mice overexpressing BCL-2. Neurosci Lett 262:33–36PubMedGoogle Scholar
  64. 64.
    Yang J, Liu X, Bhalla K, et al (1997) Prevention of apoptosis by Bcl-2: release of cytochromecfrom mitochondria blocked. Science 275:1129–1132PubMedGoogle Scholar
  65. 65.
    Mirkovic N, Voehringer DW, Story MD, et al (1997) Resistance to radiation-induced apoptosis in Bcl-2-expressing cells is reversed by depleting cellular thiols. Oncogene 15:1461–1470PubMedGoogle Scholar
  66. 66.
    Decaudin D, Geley S, Hirsch T, et al (1997) Bcl-2 and Bcl-XL antagonize the mitochondrial dysfunction preceding nuclear apoptosis induced by chemotherapeutic agents. Cancer Res 57:62–67PubMedGoogle Scholar
  67. 67.
    Rokhlin OW, Guseva N, Tagiyev A, et al (2001) Bcl-2 oncoprotein protects the human prostatic carcinoma cell line PC3 from TRAIL-mediated apoptosis. Oncogene 20:2836–2843PubMedGoogle Scholar
  68. 68.
    Sinicrope FA, Penington RC, Tang XM (2004) Tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis is inhibited by Bcl-2 but restored by the small molecule Bcl-2 inhibitor, HA 14-1, in human colon cancer cells. Clin Cancer Res 10:8284–8292PubMedGoogle Scholar
  69. 69.
    Memon SA, Moreno MB, Petrak D, Zacharchuk CM (1995) Bcl-2 blocks glucocorticoid- but not Fas- or activation-induced apoptosis in a T cell hybridoma. J Immunol 155:4644–4652PubMedGoogle Scholar
  70. 70.
    Gazitt Y, Shaughnessy P, Montgomery W (1999) Apoptosis-induced by TRAIL AND TNF-alpha in human multiple myeloma cells is not blocked by BCL-2. Cytokine 11:1010–1019PubMedGoogle Scholar
  71. 71.
    Keogh SA, Walczak H, Bouchier-Hayes L, Martin SJ (2000) Failure of Bcl-2 to block cytochromecredistribution during TRAIL-induced apoptosis. FEBS Lett 471:93–98PubMedGoogle Scholar
  72. 72.
    Veis DJ, Sorenson CM, Shutter JR, Korsmeyer SJ (1993) Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell 75:229–240PubMedGoogle Scholar
  73. 73.
    Motoyama N, Wang F, Roth KA, et al (1995) Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice. Science 267:1506–1510PubMedGoogle Scholar
  74. 74.
    Conus S, Rosse T, Bornerc(2000) Failure of Bcl-2 family members to interact with Apaf-1 in normal and apoptotic cells. Cell Death Differ 7:947–954PubMedGoogle Scholar
  75. 75.
    Murphy KM, Streips UN, Lock RB (2000) Bcl-2 inhibits a Fas-induced conformational change in the Bax N terminus and Bax mitochondrial translocation. J Biol Chem 275:17225–17228PubMedGoogle Scholar
  76. 76.
    He L, Perkins GA, Poblenz AT, et al (2003) Bcl-xL overexpression blocks bax-mediated mitochondrial contact site formation and apoptosis in rod photoreceptors of lead-exposed mice. Proc Natl Acad Sci USA 100:1022–1027PubMedGoogle Scholar
  77. 77.
    Ruffolo SC, Shore GC (2003) BCL-2 selectively interacts with the BID-induced open conformer of BAK, inhibiting BAK auto-oligomerization. J Biol Chem 278:25039–25045PubMedGoogle Scholar
  78. 78.
    Willis SN, Chen L, Dewson G, et al (2005) Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev 19:1294–1305PubMedGoogle Scholar
  79. 79.
    Ito T, Deng X, Carr B, May WS (1997) Bcl-2 phosphorylation required for anti-apoptosis function. J Biol Chem 272:11671–11673PubMedGoogle Scholar
  80. 80.
    Yamamoto K, Ichijo H, Korsmeyer SJ (1999) BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M. Mol Cell Biol 19:8469–8478PubMedGoogle Scholar
  81. 81.
    Basu A, Haldar S (2003) Identification of a novel Bcl-xL phosphorylation site regulating the sensitivity of taxol- or 2-methoxyestradiol-induced apoptosis. FEBS Lett 538:41–47PubMedGoogle Scholar
  82. 82.
    Fadeel B, Hassan Z, Hellstrom-Lindberg E, et al (1999) Cleavage of Bcl-2 is an early event in chemotherapy-induced apoptosis of human myeloid leukemia cells. Leukemia 13:719–728PubMedGoogle Scholar
  83. 83.
    Liang Y, Nylander KD, Yan C, Schor NF (2002) Role of caspase 3-dependent Bcl-2 cleavage in potentiation of apoptosis by Bcl-2. Mol Pharmacol 61:142–149PubMedGoogle Scholar
  84. 84.
    Cheng EH, Kirsch DG, Clem RJ, et al (1997) Conversion of Bcl-2 to a Bax-like death effector by caspases. Science 278:1966–1968PubMedGoogle Scholar
  85. 85.
    Kirsch DG, Doseff A, Chau BN, et al (1999) Caspase-3-dependent cleavage of Bcl-2 promotes release of cytochrome c. J Biol Chem 274:21155–21161PubMedGoogle Scholar
  86. 86.
    Basanez G, Zhang J, Chau BN, et al (2001) Pro-apoptotic cleavage products of Bcl-xL form cytochrome c-conducting pores in pure lipid membranes. J Biol Chem 276:31083–31091PubMedGoogle Scholar
  87. 87.
    Nechushtan A, Smith CL, Hsu YT, Youle RJ (1999) Conformation of the Bax C-terminus regulates subcellular location and cell death. EMBO J 18:2330–2341PubMedGoogle Scholar
  88. 88.
    Griffiths GJ, Dubrez L, Morgan CP, et al (1999) Cell damage-induced conformational changes of the pro-apoptotic protein Bak in vivo precede the onset of apoptosis. J Cell Biol 144:903–914PubMedGoogle Scholar
  89. 89.
    Mandic A, Viktorsson K, Strandberg L, et al (2002) Calpain-mediated Bid cleavage and calpain-independent Bak modulation: two separate pathways in cisplatin-induced apoptosis. Mol Cell Biol 22:3003–3013PubMedGoogle Scholar
  90. 90.
    Wei MC, Zong WX, Cheng EH, et al (2001) Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292:727–730PubMedGoogle Scholar
  91. 91.
    Deng Y, Lin Y, Wu X (2002) TRAIL-induced apoptosis requires Bax-dependent mitochondrial release of Smac/DIABLO. Genes Dev 16:33–45PubMedGoogle Scholar
  92. 92.
    Han J, Goldstein LA, Gastman BR, et al (2004) Differential involvement of Bax and Bak in TRAIL-mediated apoptosis of leukemic T cells. Leukemia 18:1671–1680PubMedGoogle Scholar
  93. 93.
    Ruiz-Vela A, Opferman JT, Cheng EH, Korsmeyer SJ (2005) Proapoptotic BAX and BAK control multiple initiator caspases. EMBO Rep 6:379–385PubMedGoogle Scholar
  94. 94.
    Wood DE, Thomas A, Devi LA, et al (1998) Bax cleavage is mediated by calpain during drug-induced apoptosis. Oncogene 17:1069–1078PubMedGoogle Scholar
  95. 95.
    Cao X, Deng X, May WS (2003) Cleavage of Bax to p18 Bax accelerates stress-induced apoptosis, and a cathepsin-like protease may rapidly degrade p18 Bax. Blood 102:2605–2614PubMedGoogle Scholar
  96. 96.
    Letai A (2003) BH3 domains as BCL-2 inhibitors: prototype cancer therapeutics. Expert Opin Biol Ther 3:293–304PubMedGoogle Scholar
  97. 97.
    Datta SR, Dudek H, Tao X, et al (1997) Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91:231–241PubMedGoogle Scholar
  98. 98.
    Datta SR, Katsov A, Hu L, et al (2000) 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation. Mol Cell 6:41–51PubMedGoogle Scholar
  99. 99.
    Konishi Y, Lehtinen M, Donovan N, Bonni A (2002) Cdc2 phosphorylation of BAD links the cell cycle to the cell death machinery. Mol Cell 9:1005–1016PubMedGoogle Scholar
  100. 100.
    Donovan N, Becker EB, Konishi Y, Bonni A (2002) JNK phosphorylation and activation of BAD couples the stress-activated signaling pathway to the cell death machinery. J Biol Chem 277:40944–40949PubMedGoogle Scholar
  101. 101.
    Dramsi S, Scheid MP, Maiti A, et al (2002) Identification of a novel phosphorylation site, Ser-170, as a regulator of bad pro-apoptotic activity. J Biol Chem 277:6399–6405PubMedGoogle Scholar
  102. 102.
    Putcha GV, Le S, Frank S, et al (2003) JNK-mediated BIM phosphorylation potentiates BAX-dependent apoptosis. Neuron 38:899–914PubMedGoogle Scholar
  103. 103.
    Nakano K, Vousden KH (2001) PUMA, a novel proapoptotic gene, is induced by p53. Mol Cell 7:683–694PubMedGoogle Scholar
  104. 104.
    Oda E, Ohki R, Murasawa H, et al (2000) Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 288:1053–1058PubMedGoogle Scholar
  105. 105.
    Yu J, Zhang L, Hwang PM, et al (2001) PUMA induces the rapid apoptosis of colorectal cancer cells. Mol Cell 7:673–682PubMedGoogle Scholar
  106. 106.
    Yu J, Wang Z, Kinzler KW, et al (2003) PUMA mediates the apoptotic response to p53 in colorectal cancer cells. Proc Natl Acad Sci USA 100:1931–1936PubMedGoogle Scholar
  107. 107.
    Li H, Zhu H, Xu CJ, Yuan J (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94:491–501PubMedGoogle Scholar
  108. 108.
    Gross A, Yin XM, Wang K, et al (1999) Caspase cleaved BID targets mitochondria and is required for cytochromecrelease, while BCL-XL prevents this release but not tumor necrosis factor-R1/Fas death. J Biol Chem 274:1156–1163PubMedGoogle Scholar
  109. 109.
    Zha J, Weiler S, Oh KJ, et al (2000) Posttranslational N-myristoylation of BID as a molecular switch for targeting mitochondria and apoptosis. Science 290:1761–1765PubMedGoogle Scholar
  110. 110.
    Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362:801–809PubMedGoogle Scholar
  111. 111.
    Kutuk O, Basaga H (2003) Inflammation meets oxidation: NF-kappaB as a mediator of initial lesion development in atherosclerosis. Trends Mol Med 9:549–557PubMedGoogle Scholar
  112. 112.
    Masuda J, Ross R (1990) Atherogenesis during low level hypercholesterolemia in the nonhuman primate. I. Fatty streak formation. Arteriosclerosis 10:164–177Google Scholar
  113. 113.
    Pauletto P, Sartore S, Pessina AC (1994) Smooth-muscle-cell proliferation and differentiation in neointima formation and vascular restenosis. Clin Sci 87:467–479PubMedGoogle Scholar
  114. 114.
    Ross R (1999) Atherosclerosis-an inflammatory disease. N Engl J Med 340:115–126PubMedGoogle Scholar
  115. 115.
    Alvarez RJ, Gips SJ, Moldovan N, et al (1997) 17beta-estradiol inhibits apoptosis of endothelial cells. Biochem Biophys Res Commun 237:372–381PubMedGoogle Scholar
  116. 116.
    Bennett MR, Evan GI, Schwartz SM (1995) Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques. J Clin Invest 95:2266–2274PubMedGoogle Scholar
  117. 117.
    Soldani C, Scovassi AI, Canosi U, et al (2005) Multicolor fluorescence technique to detect apoptotic cells in advanced coronary atherosclerotic plaques. Eur J Histochem 49:47–52PubMedGoogle Scholar
  118. 118.
    Lee HS, Chang JS, Baek JA, et al (2005) TNF-alpha activates death pathway in human aorta smooth muscle cell in the presence of 7-ketocholesterol. Biochem Biophys Res Commun 333:1093–1099PubMedGoogle Scholar
  119. 119.
    Michowitz Y, Goldstein E, Roth A, et al (2005) The involvement of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in atherosclerosis. J Am Coll Cardiol 45:1018–1024PubMedGoogle Scholar
  120. 120.
    Takarada S, Imanishi T, Hano T, Nishio I (2003) Oxidized low-density lipoprotein sensitizes human vascular smooth muscle cells to FAS (CD95)-mediated apoptosis. Clin Exp Pharmacol Physiol 30:289–294PubMedGoogle Scholar
  121. 121.
    Kockx MM, De Meyer GR, Muhring J, et al (1998) Apoptosis and related proteins in different stages of human atherosclerotic plaques. Circulation 97:2307–2315PubMedGoogle Scholar
  122. 122.
    Saxena A, McMeekin JD, Thomson DJ (2002) Expression of Bcl-x, Bcl-2, Bax, and Bak in endarterectomy and atherectomy specimens. J Pathol 196:335–342PubMedGoogle Scholar
  123. 123.
    Pollman MJ, Hall JL, Mann MJ, et al (1998) Inhibition of neointimal cell bcl-x expression induces apoptosis and regression of vascular disease. Nat Med 4:222–227PubMedGoogle Scholar
  124. 124.
    Krajewski S, Krajewska M, Shabaik A, et al (1994) Immunohistochemical determination ofin vivo distribution of Bax, a dominant inhibitor of Bcl-2. Am J Pathol 145:1323–1336PubMedGoogle Scholar
  125. 125.
    Molostvov G, Morris A, Rose P, Basu S (2002) Modulation of Bcl-2 family proteins in primary endothelial cells during apoptosis. Pathophysiol Haemost Thromb 32:85–91PubMedGoogle Scholar
  126. 126.
    Messmer UK, Briner VA, Pfeilschifter J (1999) Tumor necrosis factor-alpha and lipopolysaccharide induce apoptotic cell death in bovine glomerular endothelial cells. Kidney Int 55:2322–2337PubMedGoogle Scholar
  127. 127.
    Badrichani AZ, Stroka DM, Bilbao G, et al (1999) Bcl-2 and Bcl-XL serve an anti-inflammatory function in endothelial cells through inhibition of NF-kappaB. J Clin Invest 103:543–553PubMedGoogle Scholar
  128. 128.
    Ackermann EJ, Taylor JK, Narayana R, Bennett CF (1999) The role of antiapoptotic Bcl-2 family members in endothelial apoptosis elucidated with antisense oligonucleotides. J Biol Chem 274:11245–11252PubMedGoogle Scholar
  129. 129.
    Grethe S, Ares MP, Andersson T, Porn-Ares MI (2004) p38 MAPK mediates TNF-induced apoptosis in endothelial cells via phosphorylation and downregulation of Bcl-x(L). Exp Cell Res 298:632–642PubMedGoogle Scholar
  130. 130.
    Kim HH, Kim K (2003) Enhancement of TNF-alpha-mediated cell death in vascular smooth muscle cells through cytochrome c-independent pathway by the proteasome inhibitor. FEBS Lett 535:190–194PubMedGoogle Scholar
  131. 131.
    Sata M, Walsh K (1998) Oxidized LDL activates Fas-mediated endothelial cell apoptosis. J Clin Invest 102:1682–1689PubMedCrossRefGoogle Scholar
  132. 132.
    Sata M, Suhara T, Walsh K (2000) Vascular endothelial cells and smooth muscle cells differ in expression of Fas and Fas ligand and in sensitivity to Fas ligand-induced cell death: implications for vascular disease and therapy. Arterioscler Thromb Vasc Biol 20:309–316PubMedGoogle Scholar
  133. 133.
    Chen J, Mehta JL, Haider N, et al (2004) Role of caspases in Ox-LDL-induced apoptotic cascade in human coronary artery endothelial cells. Circ Res 94:370–376PubMedGoogle Scholar
  134. 134.
    Vicca S, Massy ZA, Hennequin C, et al (2003) Apoptotic pathways involved in U937 cells exposed to LDL oxidized by hypochlorous acid. Free Radic Biol Med 35:603–615PubMedGoogle Scholar
  135. 135.
    Kataoka H, Kume N, Miyamoto S, et al (2001) Oxidized LDL modulates Bax/Bcl-2 through the lectinlike Ox-LDL receptor-1 in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 21:955–960PubMedGoogle Scholar
  136. 136.
    Yao PM, Tabas I (2001) Free cholesterol loading of macrophages is associated with widespread mitochondrial dysfunction and activation of the mitochondrial apoptosis pathway. J Biol Chem 276:42468–42476PubMedGoogle Scholar
  137. 137.
    Liu J, Thewke DP, Su YR, et al (2005) Reduced macrophage apoptosis is associated with accelerated atherosclerosis in low-density lipoprotein receptor-null mice. Arterioscler Thromb Vasc Biol 25:174–179PubMedGoogle Scholar
  138. 138.
    Rusinol AE, Thewke D, Liu J, et al (2004) AKT/protein kinase B regulation of BCL family members during oxysterol-induced apoptosis. J Biol Chem 279:1392–1399PubMedGoogle Scholar
  139. 139.
    Napoli C, Quehenberger O, De Nigris F, et al (2000) Mildly oxidized low density lipoprotein activates multiple apoptotic signaling pathways in human coronary cells. FASEB J 14:1996–2007PubMedGoogle Scholar
  140. 140.
    Meilhac O, Escargueil-Blanc I, Thiers JC, et al (1999) Bcl-2 alters the balance between apoptosis and necrosis, but does not prevent cell death induced by oxidized low density lipoproteins. FASEB J 13:485–494PubMedGoogle Scholar
  141. 141.
    Hufnagel B, Dworak M, Soufi M, et al (2005) Unsaturated fatty acids isolated from human lipoproteins activate protein phosphatase type 2Cbeta and induce apoptosis in endothelial cells. Atherosclerosis. 180:245–254PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  1. 1.Biological Sciences and Bioengineering Program, Faculty of Engineering and Natural SciencesSabanci UniversityIstanbulTurkey

Personalised recommendations