Apoptosis-inducing Factor Substitutes for Caspase Executioners in NMDA-triggered Excitotoxic Neuronal Death

Overview

Journal J Neurosci

Specialty Neurology

Date 2004 Dec 3

PMID 15574746

Citations 116

Authors

Hongmin Wang

Seong-Woon Yu

David W Koh

Jasmine Lew

Carmen Coombs

William Bowers

Howard J Federoff

Guy G Poirier

Ted M Dawson

Valina L Dawson

Affiliations

Soon will be listed here.

Abstract

The profound neuroprotection observed in poly(ADP-ribose) polymerase-1 (PARP-1) null mice to ischemic and excitotoxic injury positions PARP-1 as a major mediator of neuronal cell death. We report here that apoptosis-inducing factor (AIF) mediates PARP-1-dependent glutamate excitotoxicity in a caspase-independent manner after translocation from the mitochondria to the nucleus. In primary murine cortical cultures, neurotoxic NMDA exposure triggers AIF translocation, mitochondrial membrane depolarization, and phosphatidyl serine exposure on the cell surface, which precedes cytochrome c release and caspase activation. NMDA neurotoxicity is not affected by broad-spectrum caspase inhibitors, but it is prevented by Bcl-2 overexpression and a neutralizing antibody to AIF. These results link PARP-1 activation with AIF translocation in NMDA-triggered excitotoxic neuronal death and provide a paradigm in which AIF can substitute for caspase executioners.

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References

Masutani M, Suzuki H, Kamada N, Watanabe M, Ueda O, Nozaki T . Poly(ADP-ribose) polymerase gene disruption conferred mice resistant to streptozotocin-induced diabetes. Proc Natl Acad Sci U S A. 1999; 96(5):2301-4. PMC: 26778. DOI: 10.1073/pnas.96.5.2301. View

Burkart V, Wang Z, Radons J, Heller B, Herceg Z, Stingl L . Mice lacking the poly(ADP-ribose) polymerase gene are resistant to pancreatic beta-cell destruction and diabetes development induced by streptozocin. Nat Med. 1999; 5(3):314-9. DOI: 10.1038/6535. View

Mandir A, Przedborski S, Jackson-Lewis V, Wang Z, Simbulan-Rosenthal C, Smulson M . Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Proc Natl Acad Sci U S A. 1999; 96(10):5774-9. PMC: 21936. DOI: 10.1073/pnas.96.10.5774. View

Pieper A, Verma A, Zhang J, Snyder S . Poly (ADP-ribose) polymerase, nitric oxide and cell death. Trends Pharmacol Sci. 1999; 20(4):171-81. DOI: 10.1016/s0165-6147(99)01292-4. View

Affar E, Duriez P, Shah R, Winstall E, Germain M, Boucher C . Immunological determination and size characterization of poly(ADP-ribose) synthesized in vitro and in vivo. Biochim Biophys Acta. 1999; 1428(2-3):137-46. DOI: 10.1016/s0304-4165(99)00054-9. View

Oliver F, Nacci C, Decker P, Andriantsitohaina R, Muller S, de La Rubia G . Resistance to endotoxic shock as a consequence of defective NF-kappaB activation in poly (ADP-ribose) polymerase-1 deficient mice. EMBO J. 1999; 18(16):4446-54. PMC: 1171519. DOI: 10.1093/emboj/18.16.4446. View

Ha H, Snyder S . Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion. Proc Natl Acad Sci U S A. 1999; 96(24):13978-82. PMC: 24176. DOI: 10.1073/pnas.96.24.13978. View

Daugas E, Susin S, Zamzami N, Ferri K, Irinopoulou T, Larochette N . Mitochondrio-nuclear translocation of AIF in apoptosis and necrosis. FASEB J. 2000; 14(5):729-39. View

Sallmann F, Vodenicharov M, Wang Z, Poirier G . Characterization of sPARP-1. An alternative product of PARP-1 gene with poly(ADP-ribose) polymerase activity independent of DNA strand breaks. J Biol Chem. 2000; 275(20):15504-11. DOI: 10.1074/jbc.275.20.15504. View

10.

Pieper A, Walles T, Wei G, Clements E, Verma A, Snyder S . Myocardial postischemic injury is reduced by polyADPripose polymerase-1 gene disruption. Mol Med. 2000; 6(4):271-82. PMC: 1949947. View

11.

Mandir A, Poitras M, Berliner A, Herring W, Guastella D, Feldman A . NMDA but not non-NMDA excitotoxicity is mediated by Poly(ADP-ribose) polymerase. J Neurosci. 2000; 20(21):8005-11. PMC: 6772735. View

12.

Olive P, Durand R, Banath J, Johnston P . Analysis of DNA damage in individual cells. Methods Cell Biol. 2000; 64:235-49. DOI: 10.1016/s0091-679x(01)64016-0. View

13.

Miramar M, Costantini P, Ravagnan L, Saraiva L, Haouzi D, Brothers G . NADH oxidase activity of mitochondrial apoptosis-inducing factor. J Biol Chem. 2001; 276(19):16391-8. DOI: 10.1074/jbc.M010498200. View

14.

Bowers W, Howard D, Brooks A, Halterman M, Federoff H . Expression of vhs and VP16 during HSV-1 helper virus-free amplicon packaging enhances titers. Gene Ther. 2001; 8(2):111-20. DOI: 10.1038/sj.gt.3301340. View

15.

Sattler R, Tymianski M . Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death. Mol Neurobiol. 2002; 24(1-3):107-29. DOI: 10.1385/MN:24:1-3:107. View

16.

Lynch D, Guttmann R . Excitotoxicity: perspectives based on N-methyl-D-aspartate receptor subtypes. J Pharmacol Exp Ther. 2002; 300(3):717-23. DOI: 10.1124/jpet.300.3.717. View

17.

Schreiber V, Ame J, Dolle P, Schultz I, Rinaldi B, Fraulob V . Poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in association with PARP-1 and XRCC1. J Biol Chem. 2002; 277(25):23028-36. DOI: 10.1074/jbc.M202390200. View

18.

Yu S, Wang H, Poitras M, Coombs C, Bowers W, Federoff H . Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science. 2002; 297(5579):259-63. DOI: 10.1126/science.1072221. View

19.

Cregan S, Fortin A, MacLaurin J, Callaghan S, Cecconi F, Yu S . Apoptosis-inducing factor is involved in the regulation of caspase-independent neuronal cell death. J Cell Biol. 2002; 158(3):507-17. PMC: 2173837. DOI: 10.1083/jcb.200202130. View

20.

Klein J, Longo-Guess C, Rossmann M, Seburn K, Hurd R, Frankel W . The harlequin mouse mutation downregulates apoptosis-inducing factor. Nature. 2002; 419(6905):367-74. DOI: 10.1038/nature01034. View