MAC inhibitors suppress mitochondrial apoptosis
Tóm tắt
MAC (mitochondrial apoptosis-induced channel) forms in the mitochondrial outer membrane and unleashes cytochrome c to orchestrate the execution of the cell. MAC opening is the commitment step of intrinsic apoptosis. Hence closure of MAC may prevent apoptosis. Compounds that blocked the release of fluorescein from liposomes by recombinant Bax were tested for their ability to directly close MAC and suppress apoptosis in FL5.12 cells. Low doses of these compounds (IC50 values ranged from 19 to 966 nM) irreversibly closed MAC. These compounds also blocked cytochrome c release and halted the onset of apoptotic markers normally induced by IL-3 (interleukin-3) deprivation or staurosporine. Our results reveal the tight link among MAC activity, cytochrome c release and apoptotic death, and indicate this mitochondrial channel is a promising therapeutic target.
Từ khóa
Tài liệu tham khảo
Arends, 1991, Apoptosis: mechanisms and roles in pathology, Int. Rev. Exp. Pathol., 32, 223, 10.1016/B978-0-12-364932-4.50010-1
Thompson, 1995, Apoptosis in the pathogenesis and treatment of disease, Science, 267, 1456, 10.1126/science.7878464
Dejean, 2006, Is MAC the knife that cuts cytochrome c from mitochondria during apoptosis?, Cell Death Differ., 13, 1387, 10.1038/sj.cdd.4401949
Martinou, 2006, Which came first, the cytochrome c release or the mitochondrial fission?, Cell Death Differ., 13, 1291, 10.1038/sj.cdd.4401985
Martinou, 2001, Breaking the mitochondrial barrier, Nat. Rev. Mol. Cell. Biol., 2, 63, 10.1038/35048069
Gross, 1999, Caspase cleaved BID targets mitochondria and is required for cytochrome c release, while BCL-XL prevents this release but not tumor necrosis factor-R1/Fas death, J. Biol. Chem., 274, 1156, 10.1074/jbc.274.2.1156
Jurgensmeier, 1998, Bax directly induces release of cytochrome c from isolated mitochondria, Proc. Natl. Acad. Sci. U.S.A., 95, 4997, 10.1073/pnas.95.9.4997
Li, 1998, Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis, Cell, 94, 491, 10.1016/S0092-8674(00)81590-1
Luo, 1998, Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors, Cell, 94, 481, 10.1016/S0092-8674(00)81589-5
Earnshaw, 1995, Nuclear changes in apoptosis, Curr. Opin. Cell Biol., 7, 337, 10.1016/0955-0674(95)80088-3
Kroemer, 2008, Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009, Cell Death Differ., 16, 3, 10.1038/cdd.2008.150
Yu, 2008, Enhancement of hyperthermia-induced apoptosis by a new synthesized class of benzocycloalkene compounds, Apoptosis, 13, 448, 10.1007/s10495-008-0178-9
Bossy-Wetzel, 1998, Mitochondrial cytochrome c release in apoptosis occurs upstream of DEVD-specific caspase activation and independently of mitochondrial transmembrane depolarization, EMBO J., 17, 37, 10.1093/emboj/17.1.37
Martin-Latil, 2007, Bax is activated during rotavirus-induced apoptosis through the mitochondrial pathway, J. Virol., 81, 4457, 10.1128/JVI.02344-06
Duan, 2003, Mitochondrial outer membrane permeability change and hypersensitivity to digitonin early in staurosporine-induced apoptosis, J. Biol. Chem., 278, 1346, 10.1074/jbc.M209269200
Yoshikawa, 2003, Caspase-dependent and -independent apoptosis of mast cells induced by withdrawal of IL-3 is prevented by Toll-like receptor 4-mediated lipopolysaccharide stimulation, Eur. J. Immunol., 33, 2149, 10.1002/eji.200323270
Pavlov, 2001, A novel, high conductance channel of mitochondria linked to apoptosis in mammalian cells and Bax expression in yeast, J. Cell Biol., 155, 725, 10.1083/jcb.200107057
Kinnally, 2007, A tale of two mitochondrial channels, MAC and PTP, in apoptosis, Apoptosis, 12, 857, 10.1007/s10495-007-0722-z
Dejean, 2006, Regulation of the mitochondrial apoptosis-induced channel, MAC, by BCL-2 family proteins, Biochim. Biophys. Acta, 1762, 191, 10.1016/j.bbadis.2005.07.002
Martinez-Caballero, 2005, The role of the mitochondrial apoptosis induced channel MAC in cytochrome c release, J. Bioenerg. Biomembr., 37, 155, 10.1007/s10863-005-6570-z
Dejean, 2005, Oligomeric Bax is a component of the putative cytochrome c release channel MAC, mitochondrial apoptosis-induced channel, Mol. Biol. Cell, 16, 2424, 10.1091/mbc.e04-12-1111
Martinez-Caballero, 2009, Assembly of the mitochondrial apoptosis-induced channel, MAC, J. Biol. Chem., 284, 12235, 10.1074/jbc.M806610200
Rapak, 2007, Apoptosis of lymphoma cells is abolished due to blockade of cytochrome c release despite Nur77 mitochondrial targeting, Apoptosis, 12, 1873, 10.1007/s10495-007-0107-3
Zhokhov, 2008, Bax siRNA promotes survival of cultured and allografted granule cell precursors through blockade of caspase-3 cleavage, Cell Death Differ., 15, 1042, 10.1038/cdd.2008.29
Andersen, 2006, HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT, PLoS Pathog., 2, e127, 10.1371/journal.ppat.0020127
Fernandez Larrosa, 2008, Apoptosis resistance in HIV-1 persistently-infected cells is independent of active viral replication and involves modulation of the apoptotic mitochondrial pathway, Retrovirology, 5, 19, 10.1186/1742-4690-5-19
Cao, 2006, Recombinant human granulocyte colony-stimulating factor protects against MPTP-induced dopaminergic cell death in mice by altering Bcl-2/Bax expression levels, J. Neurochem., 99, 861, 10.1111/j.1471-4159.2006.04125.x
Broekemeier, 1989, Cyclosporin A is a potent inhibitor of the inner membrane permeability transition in liver mitochondria, J. Biol. Chem., 264, 7826, 10.1016/S0021-9258(18)83116-7
Bombrun, 2003, 3,6-Dibromocarbazole piperazine derivatives of 2-propanol as first inhibitors of cytochrome c release via Bax channel modulation, J. Med. Chem., 46, 4365, 10.1021/jm034107j
Hetz, 2005, Bax channel inhibitors prevent mitochondrion-mediated apoptosis and protect neurons in a model of global brain ischemia, J. Biol. Chem., 280, 42960, 10.1074/jbc.M505843200
Ghose, 1998, Prediction of hydrophobic (lipophilic) properties of small organic molecules using fragmental methods: an analysis of ALOGP and CLOGP methods, J. Phys. Chem. A, 102, 3762, 10.1021/jp980230o
Gross, 1998, Enforced dimerization of BAX results in its translocation, mitochondrial dysfunction and apoptosis, EMBO J., 17, 3878, 10.1093/emboj/17.14.3878
Guo, 2004, Effects of cytochrome c on the mitochondrial apoptosis-induced channel MAC, Am. J. Physiol. Cell Physiol., 286, C1109, 10.1152/ajpcell.00183.2003
Cheng, 2003, VDAC2 inhibits BAK activation and mitochondrial apoptosis, Science, 301, 513, 10.1126/science.1083995
Decker, 1977, Ultrastructural and biochemical studies of mitoplasts and outer membranes derived from French-pressed mitochondria: advances in mitochondrial subfractionation, J. Ultrastruct. Res., 59, 44, 10.1016/S0022-5320(77)80027-0
Mannella, 1982, Structure of the outer mitochondrial membrane: ordered arrays of porelike subunits in outer-membrane fractions from Neurospora crassa mitochondria, J. Cell Biol., 94, 680, 10.1083/jcb.94.3.680
Martinez-Caballero, 2004, Some amphiphilic cations block the mitochondrial apoptosis-induced channel, MAC, FEBS Lett., 568, 35, 10.1016/j.febslet.2004.05.006
Wei, 2001, Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death, Science, 292, 727, 10.1126/science.1059108
Siskind, 2008, Anti-apoptotic Bcl-2 family proteins disassemble ceramide channels, J. Biol. Chem., 283, 6622, 10.1074/jbc.M706115200
Bernardi, 2007, The mitochondrial permeability transition pore, Novartis Found. Symp., 287, 157, 10.1002/9780470725207.ch11
Zhang, 2006, Bax and the mitochondrial permeability transition cooperate in the release of cytochrome c during endoplasmic reticulum-stress-induced apoptosis, Cell Death Differ., 14, 703, 10.1038/sj.cdd.4402072
Lindsten, 2006, Cell death in the absence of Bax and Bak, Cell Death Differ., 13, 1272, 10.1038/sj.cdd.4401953