Atorvastatin attenuates mitochondrial toxin-induced striatal degeneration, with decreasing iNOS/c-Jun levels and activating ERK/Akt pathways

Journal of Neurochemistry

Volumn 104, Issue 5, 2008, Pages 1190-1200

  Lee, Soon Tae ^a,b   Chu, Kon ^a,b   Park, Jung Eun ^a   Hong, Nan Hyung ^a   Im, Woo Seok ^a   Kang, Lami ^a   Han, Zhe ^a   Jung, Keun Hwa ^a,c   Kim, Min Wook ^d   Kim, Manho ^a,b  

^a Seoul National University Hospital   (South Korea)

^b Seoul National University   (South Korea)

^c Korea Centers for Disease Control and Prevention   (South Korea)

^d The Catholic University of Korea   (South Korea)

Author keywords

3 nitropropionic acid; Atorvastatin; Huntington's disease; Mitochondria; Neurodegeneration

Indexed keywords

3 NITROPROPIONIC ACID; 3 NITROTYROSINE; ATORVASTATIN; CYTOTOXIN; INDUCIBLE NITRIC OXIDE SYNTHASE; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN; PROTEIN C JUN; PROTEIN KINASE B;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CELL DEGENERATION; CONTROLLED STUDY; DRUG MECHANISM; LEWIS RAT; MALE; MITOCHONDRIAL MEMBRANE; NERVE DEGENERATION; NICK END LABELING; NISSL STAINING; NONHUMAN; OSMOTIC PUMP; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; RAT; STRIATE CORTEX; UPREGULATION;

ANIMALS; CORPUS STRIATUM; DISEASE MODELS, ANIMAL; ENZYME ACTIVATION; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; HEPTANOIC ACIDS; JNK MITOGEN-ACTIVATED PROTEIN KINASES; MALE; MAP KINASE SIGNALING SYSTEM; MITOCHONDRIA; NERVE DEGENERATION; NEUROTOXINS; NITRIC OXIDE SYNTHASE TYPE II; NITRO COMPOUNDS; PROPIONIC ACIDS; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-AKT; PYRROLES; RATS; RATS, INBRED LEW; RATS, SPRAGUE-DAWLEY;

ANIMALIA; RATTUS;

EID: 39749142103     PISSN: 00223042     EISSN: 14714159     Source Type: Journal    
DOI: 10.1111/j.1471-4159.2007.05044.x     Document Type: Article

References (79)

1. Amarenco P., Bogousslavsky J., Callahan A. III. et al. (2006) High-dose atorvastatin after stroke or transient ischemic attack. N. Engl. J. Med. 355, 549 559.
2. Apostol B. L., Illes K., Pallos J. et al. (2007) Mutant huntingtin alters MAPK signaling pathways in PC12 and striatal cells: ERK1/2 protects against mutant huntingtin-associated toxicity. Hum. Mol. Genet. 15, 273 285.
3. Bae B. I., Xu H., Igarashi S. et al. (2005) p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease. Neuron 47, 29 41.
4. Bantubungi K., Jacquard C., Greco A. et al. (2005) Minocycline in phenotypic models of Huntington's disease. Neurobiol. Dis. 18, 206 217.
5. Bates G. (2003) Huntingtin aggregation and toxicity in Huntington's disease. Lancet 361, 1642 1644.
6. Beal M. F. (2005) Mitochondria take center stage in aging and neurodegeneration. Ann. Neurol. 58, 495 505.
7. Beal M. F., Brouillet E., Jenkins B. G., Ferrante R. J., Kowall N. W., Miller J. M., Storey E., Srivastava R., Rosen B. R. Hyman B. T. (1993) Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J. Neurosci. 13, 4181 4192.
8. Behrens A., Sibilia M. Wagner E. F. (1999) Amino-terminal phosphorylation of c-Jun regulates stress-induced apoptosis and cellular proliferation. Nat. Genet. 21, 326 329.
9. Bizat N., Hermel J. M., Boyer F., Jacquard C., Creminon C., Ouary S., Escartin C., Hantraye P., Kajewski S. Brouillet E. (2003) Calpain is a major cell death effector in selective striatal degeneration induced in vivo by 3-nitropropionate: implications for Huntington's disease. J. Neurosci. 23, 5020 5030.
10. Blum D., Gall D., Cuvelier L. Schiffmann S. N. (2001) Topological analysis of striatal lesions induced by 3-nitropropionic acid in the Lewis rat. Neuroreport 12, 1769 1772.
11. Bosel J., Gandor F., Harms C. et al. (2005) Neuroprotective effects of atorvastatin against glutamate-induced excitotoxicity in primary cortical neurones. J. Neurochem. 92, 1386 1398.
12. Brouillet E., Guyot M. C., Mittoux V., Altairac S., Conde F., Palfi S. Hantraye P. (1998) Partial inhibition of brain succinate dehydrogenase by 3-nitropropionic acid is sufficient to initiate striatal degeneration in rat. J. Neurochem. 70, 794 805.
13. Brouillet E., Jacquard C., Bizat N. Blum D. (2005) 3-Nitropropionic acid: a mitochondrial toxin to uncover physiopathological mechanisms underlying striatal degeneration in Huntington's disease. J. Neurochem. 95, 1521 1540.
14. Browne S. E., Bowling A. C., MacGarvey U., Baik M. J., Berger S. C., Muqit M. M., Bird E. D. Beal M. F. (1997) Oxidative damage and metabolic dysfunction in Huntington's disease: selective vulnerability of the basal ganglia. Ann. Neurol. 41, 646 653.
15. Browne S. E., Ferrante R. J. Beal M. F. (1999) Oxidative stress in Huntington's disease. Brain Pathol. 9, 147 163.
16. Cannon C. P., Braunwald E., McCabe C. H. et al. (2004) Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N. Engl. J. Med. 350, 1495 1504.
17. Chan P. H. (2005) Mitochondrial dysfunction and oxidative stress as determinants of cell death/survival in stroke. Ann. N. Y. Acad. Sci. 1042, 203 209.
18. Chen J., Zhang Z. G., Li Y. et al. (2003) Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke. Ann. Neurol. 53, 743 751.
19. Choo Y. S., Johnson G. V., MacDonald M., Detloff P. J. Lesort M. (2004) Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release. Hum. Mol. Genet. 13, 1407 1420.
20. Chu C. T., Levinthal D. J., Kulich S. M., Chalovich E. M. DeFranco D. B. (2004a) Oxidative neuronal injury. The dark side of ERK1/2. Eur. J. Biochem. 271, 2060 2066.
21. Chu K., Kim M., Park K. I. et al. (2004b) Human neural stem cells improve sensorimotor deficits in the adult rat brain with experimental focal ischemia. Brain Res. 1016, 145 153.
22. Colin E., Regulier E., Perrin V., Durr A., Brice A., Aebischer P., Deglon N., Humbert S. Saudou F. (2005) Akt is altered in an animal model of Huntington's disease and in patients. Eur. J. Neurosci. 21, 1478 1488.
23. Davis R. J. (2000) Signal transduction by the JNK group of MAP kinases. Cell 103, 239 252.
24. Day A. P., Bellavia S., Jones O. T. Stansbie D. (1997) Effect of simvastatin therapy on cell membrane cholesterol content and membrane function as assessed by polymorphonuclear cell NADPH oxidase activity. Ann. Clin. Biochem. 34, 269 275.
25. Deckel A. W., Gordinier A., Nuttal D., Tang V., Kuwada C., Freitas R. Gary K. A. (2001) Reduced activity and protein expression of NOS in R6/2 HD transgenic mice: effects of l-NAME on symptom progression. Brain Res. 919, 70 81.
26. DeKosky S. T. (2005) Statin therapy in the treatment of Alzheimer disease: what is the rationale? Am. J. Med. 118 (Suppl. 12A 48 53.
27. Di Napoli P., Taccardi A. A., Oliver M. De Caterina R. (2002) Statins and stroke: evidence for cholesterol-independent effects. Eur. Heart J. 23, 1908 1921.
28. Garcia M., Vanhoutte P., Pages C., Besson M. J., Brouillet E. Caboche J. (2002) The mitochondrial toxin 3-nitropropionic acid induces striatal neurodegeneration via a c-Jun N-terminal kinase/c-Jun module. J. Neurosci. 22, 2174 2184.
29. Garcia M., Charvin D. Caboche J. (2004) Expanded huntingtin activates the c-Jun terminal kinase/c-Jun pathway prior to aggregate formation in striatal neurons in culture. Neuroscience 127, 859 870.
30. Good P. F., Werner P., Hsu A., Olanow C. W. Perl D. P. (1996) Evidence of neuronal oxidative damage in Alzheimer's disease. Am. J. Pathol. 149, 21 28.
31. Gu M., Gash M. T., Mann V. M., Javoy-Agid F., Cooper J. M. Schapira A. H. (1996) Mitochondrial defect in Huntington's disease caudate nucleus. Ann. Neurol. 39, 385 389.
32. Herdegen T., Skene P. Bahr M. (1997) The c-Jun transcription factor - bipotential mediator of neuronal death, survival and regeneration. Trends Neurosci. 20, 227 231.
33. Hetman M. Gozdz A. (2004) Role of extracellular signal regulated kinases 1 and 2 in neuronal survival. Eur. J. Biochem. 271, 2050 2055.
34. Hu S., Sheng W. S., Peterson P. K. Chao C. C. (1995) Differential regulation by cytokines of human astrocyte nitric oxide production. Glia 15, 491 494.
35. Humbert S., Bryson E. A., Cordelieres F. P., Connors N. C., Datta S. R., Finkbeiner S., Greenberg M. E. Saudou F. (2002) The IGF-1/Akt pathway is neuroprotective in Huntington's disease and involves Huntingtin phosphorylation by Akt. Dev. Cell 2, 831 837.
36. Iadecola C. (1997) Bright and dark sides of nitric oxide in ischemic brain injury. Trends Neurosci. 20, 132 139.
37. Ischiropoulos H., Zhu L., Chen J., Tsai M., Martin J. C., Smith C. D. Beckman J. S. (1992) Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch. Biochem. Biophys. 298, 431 437.
38. Jeong S. W., Chu K., Jung K. H., Kim S. U., Kim M. Roh J. K. (2003) Human neural stem cell transplantation promotes functional recovery in rats with experimental intracerebral hemorrhage. Stroke 34, 2258 2263.
39. Jick H., Zornberg G. L., Jick S. S., Seshadri S. Drachman D. A. (2000) Statins and the risk of dementia. Lancet 356, 1627 1631.
40. Jones S. P., Teshima Y., Akao M. Marban E. (2003) Simvastatin attenuates oxidant-induced mitochondrial dysfunction in cardiac myocytes. Circ. Res. 93, 697 699.
41. Jung K. H., Chu K., Jeong S. W., Han S. Y., Lee S. T., Kim J. Y., Kim M. Roh J. K. (2004) HMG-CoA reductase inhibitor, atorvastatin, promotes sensorimotor recovery, suppressing acute inflammatory reaction after experimental intracerebral hemorrhage. Stroke 35, 1744 1749.
42. Landles C. Bates G. P. (2004) Huntingtin and the molecular pathogenesis of Huntington's disease. Fourth in molecular medicine review series. EMBO Rep. 5, 958 963.
43. Laufs U., Gertz K., Huang P., Nickenig G., Bohm M., Dirnagl U. Endres M. (2000) Atorvastatin upregulates type III nitric oxide synthase in thrombocytes, decreases platelet activation, and protects from cerebral ischemia in normocholesterolemic mice. Stroke 31, 2442 2449.
44. Lee S. T. Kim M. (2006) Aging and neurodegeneration. Molecular mechanisms of neuronal loss in Huntington's disease. Mech. Ageing Dev. 127, 432 435.
45. Lee S. T., Chu K., Park J. E., Kang L., Ko S. Y., Jung K. H. Kim M. (2006a) Memantine reduces striatal cell death with decreasing calpain level in 3-nitropropionic model of Huntington's disease. Brain Res. 1118, 199 207.
46. Lee S. T., Chu K., Jung K. H., Kim J., Kim E. H., Kim S. J., Sinn D. I., Ko S. Y., Kim M. Roh J. K. (2006b) Memantine reduces hematoma expansion in experimental intracerebral hemorrhage, resulting in functional improvement. J. Cereb. Blood Flow Metab. 26, 536 544.
47. Lefer A. M., Scalia R. Lefer D. J. (2001) Vascular effects of HMG CoA-reductase inhibitors (statins) unrelated to cholesterol lowering: new concepts for cardiovascular disease. Cardiovasc. Res. 49, 281 287.
48. Li L., Cao D., Kim H., Lester R. Fukuchi K. (2006) Simvastatin enhances learning and memory independent of amyloid load in mice. Ann. Neurol. 60, 729 739.
49. Lin M. T. Beal M. F. (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443, 787 795.
50. Liu Y. F., Dorow D. Marshall J. (2000) Activation of MLK2-mediated signaling cascades by polyglutamine-expanded huntingtin. J. Biol. Chem. 275, 19035 19040.
51. Ludolph A. C., He F., Spencer P. S., Hammerstad J. Sabri M. (1991) 3-Nitropropionic acid-exogenous animal neurotoxin and possible human striatal toxin. Can. J. Neurol. Sci. 18, 492 498.
52. Lustbader J. W., Cirilli M., Lin C. et al. (2004) ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease. Science 304, 448 452.
53. Manning A. M. Davis R. J. (2003) Targeting JNK for therapeutic benefit: from junk to gold? Nat. Rev. Drug Discov. 2, 554 565.
54. Maron D. J., Fazio S. Linton M. F. (2000) Current perspectives on statins. Circulation 101, 207 213.
55. Martin L. J., Pan Y., Price A. C., Sterling W., Copeland N. G., Jenkins N. A., Price D. L. Lee M. K. (2006) Parkinson's disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death. J. Neurosci. 26, 41 50.
56. Matsushita K., Meng W., Wang X., Asahi M., Asahi K., Moskowitz M. A. Lo E. H. (2000) Evidence for apoptosis after intercerebral hemorrhage in rat striatum. J. Cereb. Blood Flow Metab. 20, 396 404.
57. Mayo L. D. Donner D. B. (2001) A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc. Natl. Acad. Sci. USA 98, 11598 11603.
58. Mittoux V., Ouary S., Monville C. et al. (2002) Corticostriatopallidal neuroprotection by adenovirus-mediated ciliary neurotrophic factor gene transfer in a rat model of progressive striatal degeneration. J. Neurosci. 22, 4478 4486.
59. Nishino H., Fujimoto I., Shimano Y., Hida H., Kumazaki M. Fukuda A. (1996) 3-Nitropropionic acid produces striatum selective lesions accompanied by iNOS expression. J. Chem. Neuroanat. 10, 209 212.
60. Nomura Y. (2004) Neuronal apoptosis and protection: effects of nitric oxide and endoplasmic reticulum-related proteins. Biol. Pharm. Bull. 27, 961 963.
61. Pahan K., Sheikh F. G., Namboodiri A. M. Singh I. (1997) Lovastatin and phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia, and macrophages. J. Clin. Invest. 100, 2671 2679.
62. Panov A. V., Gutekunst C. A., Leavitt B. R., Hayden M. R., Burke J. R., Strittmatter W. J. Greenamyre J. T. (2002) Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines. Nat. Neurosci. 5, 731 736.
63. Rangone H., Pardo R., Colin E., Girault J. A., Saudou F. Humbert S. (2005) Phosphorylation of arfaptin 2 at Ser260 by Akt inhibits polyQ-huntingtin-induced toxicity by rescuing proteasome impairment. J. Biol. Chem. 280, 22021 22028.
64. Rockwood K., Kirkland S., Hogan D. B., MacKnight C., Merry H., Verreault R., Wolfson C. McDowell I. (2002) Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people. Arch. Neurol. 59, 223 227.
65. Schachter M. (2005) Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam. Clin. Pharmacol. 19, 117 125.
66. Schmued L. C., Stowers C. C., Scallet A. C. Xu L. (2005) Fluoro-Jade C results in ultra high resolution and contrast labeling of degenerating neurons. Brain Res. 1035, 24 31.
67. Shen H. M. Liu Z. G. (2006) JNK signaling pathway is a key modulator in cell death mediated by reactive oxygen and nitrogen species. Free Radic. Biol. Med. 40, 928 939.
68. Stepien K., Tomaszewski M. Czuczwar S. J. (2005) Neuroprotective properties of statins. Pharmacol. Rep. 57, 561 569.
69. Tabrizi S. J., Cleeter M. W., Xuereb J., Taanman J. W., Cooper J. M. Schapira A. H. (1999) Biochemical abnormalities and excitotoxicity in Huntington's disease brain. Ann. Neurol. 45, 25 32.
70. Teunissen C. E., Markerink-van Ittersum M., de Bruijn C., Steinbusch H. W. de Vente J. (2002) Evaluation of 3-nitrotyrosine as a marker for 3-nitropropionic acid-induced oxidative stress in Lewis and Wistar rats and strain-specific whole brain spheroid cultures. Brain Res. 931, 5 20.
71. Vodovotz Y., Lucia M. S., Flanders K. C. et al. (1996) Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease. J. Exp. Med. 184, 1425 1433.
72. Wagner A. H., Kohler T., Ruckschloss U., Just I. Hecker M. (2000) Improvement of nitric oxide-dependent vasodilatation by HMG-CoA reductase inhibitors through attenuation of endothelial superoxide anion formation. Arterioscler. Thromb. Vasc. Biol. 20, 61 69.
73. Waters D. D. (2005) Safety of high-dose atorvastatin therapy. Am. J. Cardiol. 96, 69F 75F.
74. Weber M. S., Prod'homme T., Steinman L. Zamvil S. S. (2005) Drug insight: using statins to treat neuroinflammatory disease. Nat. Clin. Pract. Neurol. 1, 106 112.
75. Wolozin B., Kellman W., Ruosseau P., Celesia G. G. Siegel G. (2000) Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3- methyglutaryl coenzyme A reductase inhibitors. Arch. Neurol. 57, 1439 1443.
76. Yaffe K., Barrett-Connor E., Lin F. Grady D. (2002) Serum lipoprotein levels, statin use, and cognitive function in older women. Arch. Neurol. 59, 378 384.
77. Yamamoto A., Hoshi K. Ichihara K. (1998) Fluvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, scavenges free radicals and inhibits lipid peroxidation in rat liver microsomes. Eur. J. Pharmacol. 361, 143 149.
78. Zacco A., Togo J., Spence K., Ellis A., Lloyd D., Furlong S. Piser T. (2003) 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors protect cortical neurons from excitotoxicity. J. Neurosci. 23, 11104 11111.
79. Zhou Z., Rahme E. Pilote L. (2006) Are statins created equal? Evidence from randomized trials of pravastatin, simvastatin, and atorvastatin for cardiovascular disease prevention. Am. Heart J. 151, 273 281.