Amino Acids

, Volume 32, Issue 4, pp 527–534 | Cite as

The nuclear proteasome and the degradation of oxidatively damaged proteins

  • P. Voss
  • T. Grune
Review Article


The accumulation of oxidized proteins is known to be linked to some severe neurodegenerative diseases like Alzheimer’s, Parkinson’s and Huntington’s disease. Furthermore, the aging process is also accompanied by an ongoing aggregation of misfolded and damaged proteins. Therefore, mammalian cells have developed potent degradation systems, which selectively degrade damaged and misfolded proteins. The proteasomal system is largely responsible for the removal of oxidatively damaged proteins form the cellular environment. Not only cytosolic proteins are prone to oxidative stress, also nuclear proteins are readily oxidized. The nuclear proteasomal system is responsible for the degradation of these proteins. This review is focused on the specific degradation of oxidized nuclear proteins, the role of the proteasome in this process and the regulation of the nuclear proteasomal system under oxidative conditions.

Keywords: Protein oxidation – Protein degradation – Proteasome – Nucleus – Histone – PARP 



Alzheimer’s disease




advanced glycosilation end products




desoxyribonucleic acid


epidermal growth factor


endoplasmic reticulum


glucose-6-phosphate dehydrogenase


glyceraldehyde-3-phosphate dehydrogenase


Huntington’s disease




interferon γ




major histocompatibility complex class I


nicotinamide adenosine dinucleotide


nuclear localization signal




poly-(ADP-ribose) polymerase


Parkinson’s disease


reactive nitrogen species


reactive oxygen species


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  1. Aki, M, Shimbara, N, Takashina, M, Akiyama, K, Kagawa, S, Tamurea, T, Tanahashi, N, Yoshimura, T, Tanaka, K, Ichihara, A 1994Interferon-gamma induces different subunit organizations and functional diversity of proteasomesJ Biochem115257269PubMedGoogle Scholar
  2. Arnold, J, Grune, T 2002PARP-mediated proteasome activation: a co-ordination of DNA repair and protein degradation?BioEssays2410601065PubMedGoogle Scholar
  3. Bajorek, M, Glickman, MH 2004Keepers at the final gates: regulatory complexes and gating of the proteasomal channelCell Mol Life Sci61110Google Scholar
  4. Barnham, KJ, Masters, CL, Bush, AI 2004Neurodegenerative diseases and oxidative stressNat Rev Drug Discov3205214PubMedGoogle Scholar
  5. Beedholm, R, Clark, BFC, Rattan, SIS 2004Mild heat stress stimulates 20S proteasome and its 11S activator in human fibroblasts undergoing aging in vitroCell Stress Chaperones94957PubMedGoogle Scholar
  6. Bose, S, Stratford, FL, Broadfoot, KI, Mason, GG, Rivett, AJ 2004Phosphorylation of 20S proteasome alpha subunit C8 (alpha7) stabilizes the 26S proteasome and plays a role in the regulation of proteasome complexes by gamma-interferonBiochem J378177184PubMedGoogle Scholar
  7. Bossy-Wetzel, E, Schwarzenbacher, R, Lipton, SA 2004Molecular pathways to neurodegenerationNat Med10S2S9PubMedGoogle Scholar
  8. Braun, BC, Glickman, M, Kraft, R, Dahlmann, B, Kloetzel, PM, Finley, D, Schmidt, M 1999The base of the proteasome regulatory particle exhibits chaperone-like activityNature Cell Biol1221226PubMedGoogle Scholar
  9. Brooks, P, Fuertes, G, Murray, RZ, Bose, S, Knecht, E, Rechsteiner, MC, Hendil, KB, Tanaka, K, Dyson, J, Rivett, J 2000Subcellular localization fo proteasomes and their regulatory complexes in mammalian cellsBiochem J346155161PubMedGoogle Scholar
  10. Buchczyk, DP, Grune, T, Sies, H, Klotz, LO 2003Modifications of glyceraldeyde-3-phosphate dehydrogenase induced by increasing concentrations of peroxynitrite: early recognition by 20S proteasomeBiol Chem384237241PubMedGoogle Scholar
  11. Carrard, G, Bulteau, AL, Petropoulos, I, Friguet, B 2002Impairment of proteasome structure and function in agingInt J Biochem Cell Biol3414611474PubMedGoogle Scholar
  12. Cervantes-Laurean, D, Roberts, MJ, Jacobson, EL, Jacobson, MK 2005Nuclear proteasome activation and degradation of carboxymethylated histones in human keratinocytes following glyoxal treatmentFree Radic Biol Med38786795PubMedGoogle Scholar
  13. Chu-Ping, M, Slaughter, CA, DeMartino, GN 1992Purification and characterization of a protein inhibitor of the 20S proteasome (macropain)Biochim Biophys Acta1119303311PubMedGoogle Scholar
  14. Ciechanover, A, Brundin, P 2003The ubiquitin proteasome system in neurodegenerative diseases: sometimes the chicken, sometimes the eggNeuron40427446PubMedGoogle Scholar
  15. Claverol, S, Burlet-Schiltz, O, Girbal-Neuhauser, E, Gairin, JE, Monsarrat, B 2002Mapping and structural dissection of human 20S proteasome using proteomic approachesMol Cell Proteomics1567578PubMedGoogle Scholar
  16. Coux, O, Tanaka, K, Goldberg, AL 1996Structure and function of the 20S and 26S proteasomesAnnu Rev Biochem65801847PubMedGoogle Scholar
  17. Davies, KJ 2001Degradation of oxidized proteins by the 20S proteasomeBiochimie83301310PubMedGoogle Scholar
  18. Demasi, M, Silva, GM, Netto, LE 200320S proteasome from Saccharomyces cerevisiae is responsive to redox modifications and is S-glutathionylatedJ Biol Chem378679685Google Scholar
  19. Emerit, J, Edeas, M, Bricaire, F 2004Neurodegenerative diseases and oxidative stressBiomed Pharmacother583946PubMedGoogle Scholar
  20. Enenkel, C, Lehmann, A, Kloetzel, PM 1998Subcellular distribution of proteasomes implicates a major location of protein degradation in the nuclear envelope-ER network in yeastEMBO J1761446154PubMedGoogle Scholar
  21. Evdonin, AL, Tsupkina, NV, Konstantinova, IM, Medvedeva, ND 2001Effect of EGF on nuclear-cytoplasmic distribution of proteasomes in A-431 cellsTsitologiia43142147PubMedGoogle Scholar
  22. Fenteany, G, Standaert, RF, Lane, WS, Choi, S, Corey, EJ, Schreiber, SL 1995Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystinScience268726731PubMedGoogle Scholar
  23. Friguet, B, Stadtman, ER, Szweda, LI 1994aModification of glucose-6-phosphate dehydrogenase by 4-hydroxy-2-nonenal. Formation of cross-linked protein that inhibits the multicatalytic proteaseJ Biol Chem2692163921643Google Scholar
  24. Friguet, B, Szweda, LI, Stadtman, ER 1994bSusceptibility of glucose-6-phosphat dehydrogenase modified by 4-hydroxy-2-nonenal and metal-catalyzed oxidation to proteolysis by the multicatalytic proteaseArch Biochem Biophys311168173Google Scholar
  25. Gieche, J, Mehlhase, J, Licht, A, Zacke, T, Sitte, N, Grune, T 2001Protein oxidation and proteolysis in RAW264.7 macrophages: effects of PMA activationBiochim Biophys Acta1538321328PubMedGoogle Scholar
  26. Giulivi, C, Pacifici, RE, Davies, KJA 1994Exposure of hydrophobic moieties promotes the selective degradation of hydrogen peroxide-modified hemoglobin by the multicatalytic proteinase complex, proteasomeArch Biochem Biophys311329341PubMedGoogle Scholar
  27. Glickman, MH, Maytal, V 2002Regulating the 26S proteasomeZwickl, PBaumeister, W eds. The proteasome-ubiquitin protein degradation pathwaySpringerBerlin Heidelberg4362Google Scholar
  28. Goldberg, AL 2003Protein degradation and protection against misfolded or damaged proteinsNature426895899PubMedGoogle Scholar
  29. Groll, M, Ditzel, I, Löwe, J, Stock, D, Bochtler, M, Bartunik, HD, Huber, R 1997Structure of 20S proteasome form yeast at 2.4 Å resolutionNature386463471PubMedGoogle Scholar
  30. Groll, M, Kim, KB, Kairies, N, Huber, R, Crews, CM 2000Crystal structure of epoxymicin: 20S proteasome reveals a molecular basis for selectivity of α′,β′-epoxyketone proteasomal inhibitorsJ Am Chem Soc12212371238Google Scholar
  31. Grune, T 2003Protein oxidation in the aging of skin fibroblastsHautarzt54818821PubMedGoogle Scholar
  32. Grune, T, Blasig, IE, Sitte, N, Roloff, B, Haseloff, R, Davies, KJ 1998Peroxynitrite increases the degradation of aconitase and other cellular proteins by proteasomeJ Biol Chem2731085710862PubMedGoogle Scholar
  33. Grune, T, Davies, KJ 2003The proteasomal system and HNE-modified proteinsMol Aspects Med24195204PubMedGoogle Scholar
  34. Grune, T, Klotz, LO, Gieche, J, Rudeck, M, Sies, H 2001Protein oxidation and proteolysis by the nonradical oxidants singlet oxygen or peroxynitriteFree Radic Biol Med3012431253PubMedGoogle Scholar
  35. Grune, T, Reinheckel, T, Davies, KJ 1996Degradation of oxidized proteins in K562 human hematopoietic cells by proteasomeJ Biol Chem2711550415509PubMedGoogle Scholar
  36. Grune, T, Reinheckel, T, Joshi, M, Davies, KJ 1995Proteolysis in cultured liver epithelial cells during oxidative stress. Role of the multicatalytic proteinase complex, proteasomeJ Biol Chem27023442351PubMedGoogle Scholar
  37. Grune, T, Reinheckel, T, Li, R, North, JA, Davies, KJ 2002Proteasome-dependent turnover of protein disulfide isomerase in oxidatively stressed cellsArch Biochem Biophys397407413PubMedGoogle Scholar
  38. Harper, JW, Powers, JC 1985Reaction of serine proteases with substituted 3-alkoxy-4-chloroisocoumarins and 3-alkoxy-7-amino-4-chloroisocoumarins: new reactive mechanism-based inhibitorsBiochemistry2572007213Google Scholar
  39. Hill, CP, MAsters, EI, Whitby, FG 2002The 11S regulators of 20S proteasome activityZwickl, PBaumeister, W eds. The proteasome-ubiquitin protein degradation pathwaySpringerBerlin Heidelberg7390Google Scholar
  40. Kanno, S, Shouji, A, Hirata, R, Asou, K, Ishikawa, M 2004Effects of naringin on cytosine arabinoside (Ara-C)-induced cytotoxicity and apoptosis in P388 cellsLife Sci75353365PubMedGoogle Scholar
  41. Keller, JN, Schmidt, FA, Scheff, SW, Ding, Q, Butterfield, DA, Markesberry, WR 2005Evidence of increased oxidative damage in subjects with mild cognitive impairmentNeurology6411521156PubMedGoogle Scholar
  42. Khan, M, Varadharaj, S, Shobha, JC, Naidu, MU, Parinandi, NL, Kutala, VK, Kuppusamy, P 2006C-phycocyanin ameliorates doxorubicin-induced oxidative stress and apoptosis in adult rat cardiomyocytesJ Cardiovasc Pharmacol47920PubMedGoogle Scholar
  43. Kim, HD, Tomida, A, Ogiso, Y, Tsuruo, T 1999Glucose-regulated stresses cause degeneration of DNA topoisomerase IIalpha by inducing nuclear proteasome during G1 cell cycle arrest in cancer cellsJ Cell Physiol18097104PubMedGoogle Scholar
  44. Klein, U, Gernold, M, Kloetzel, PM 1990Cell-specific accumulation of Drosophila proteasomes (MCP) during early developmentJ Cell Biol11122752282PubMedGoogle Scholar
  45. Knuehl, C, Seelig, A, Brecht, B, Henklein, P, Kloetzel, PM 1996Functional analysis of eukayotic 20S proteasome nuclear localization signalExp Cell Res2256774PubMedGoogle Scholar
  46. Kohno, J, Koguchi, Y, Niskio, M, Nakao, K, Kuroda, M, Shimizu, R, Ohnuki, T, Komatsubara, S 2000Structures of TMC-95A-D: novel proteasome inhibitors from Apoispore montagnei Sacc. TC 1093J Org Chem65990995PubMedGoogle Scholar
  47. Kruger, E, Kloetzel, PM, Enenkel, C 200120S proteasome biogenesisBiochimie83289293PubMedGoogle Scholar
  48. Lasch, P, Petras, T, Ullrich, O, Backmann, J, Naumann, D, Grune, T 2001Hydrogen peroxide-induced structural alterations of RNAse AJ Biol Chem27694929502PubMedGoogle Scholar
  49. Lee, DH, Goldberg, AL 1996Selective inhibitors of the proteasome-dependent and vacuolar pathways of protein degradation in Saccharomyces cerevisiaeJ Biol Chem2712728027284PubMedGoogle Scholar
  50. Lehmann, A, Janek, K, Braun, B, Kloetzel, PM, Enenkel, C 200220S proteasomes are imported as precursor complex into the nucleus of yeastJ Mol Biol317401413PubMedGoogle Scholar
  51. Li, XS, Etlinger, JD 1992Ubiquitinated proteasome inhibitor is a component of the 26S proteasome complexBiochemistry311196411967PubMedGoogle Scholar
  52. Löwe, J, Stock, D, Jap, B, Zwickl, P, Baumeister, W, Huber, R 1995Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 Å resolutionScience268533539PubMedGoogle Scholar
  53. Mayer-Kuckuk, P, Ullrich, O, Ziegler, M, Grune, T, Schweiger, M 1999Functional interaction of poly(ADP-ribose) with the 20S proteasome in vitroBiochem Biophys Res Commun259576581PubMedGoogle Scholar
  54. Mehlhase, J, Gieche, J, Ullrich, O, Sitte, N, Grune, T 2000LPS-induced protein oxidation and proteolysis in BV-2 microglial cellsIUBMB Life5015Google Scholar
  55. Mehlhase, J, Sandig, G, Pantopoulos, K, Grune, T 2005Oxidation-induced ferritin turnover in microglial cells: role of the proteasomeFree Radic Biol Med38276285PubMedGoogle Scholar
  56. Merker, K, Sitte, N, Grune, T 2000Hydrogen peroxide-mediated protein oxidation in young and old human MRC-5 fibroblastsArch Biochem Biophys3755054PubMedGoogle Scholar
  57. Merker, K, Ullrich, O, Schmidt, H, Sitte, N, Grune, T 2003Stability of the nuclear protein turnover during cellular senescence of human fibroblastsFASEB J1719631965PubMedGoogle Scholar
  58. Ogiso, Y, Tomida, A, Kim, HD, Tsuruo, T 1999Glucose starvation and hypoxia induce nuclear accumulation of proteasome in cancer cellsBiochem Biophys Res Commun258448452PubMedGoogle Scholar
  59. Ogiso, Y, Tomida, A, Tsuruo, T 2002Nuclear localization of proteasomes participates in stress-inducible resistance of solid tumor cells to topoisomerase II-directed drugsCancer Res6250085012PubMedGoogle Scholar
  60. Pacifici, RE, Kono, Y, Davies, KJA 1993Hydrophobicity as the signal for selective degradation of hydroxyl radical-modified hemoglobin by the multicatalytic proteinase complex, proteasomeJ Biol Chem2681540515411PubMedGoogle Scholar
  61. Palmer, JT, Rasnick, D, Klaus, JL, Bromme, D 1995Vinyl sulfones as mechanism-based cysteine protease inhibitoresJ Med Chem3831933196PubMedGoogle Scholar
  62. Peters, J-M, Franke, WW, Kleinschmidt, JA 1994Distinct 19S and 20S subcomplexes of the 26S proteasome and their distribution in the nucleus and the cytoplasmJ Biol Chem26977097718PubMedGoogle Scholar
  63. Rechsteiner, M, Realini, C, Ustrell, V 2000Teh proteasome activator 11S REG (PA28) and class I antigen presentationBiochem J345115PubMedGoogle Scholar
  64. Reinheckel, T, Sitte, , Ullrich, O, Kuckelkorn, U, Davies, KJ, Grune, T 1998Comparative resistance of the 20S and 26S proteasome to oxidative stressBiochem J335637642PubMedGoogle Scholar
  65. Reinheckel, T, Ullrich, O, Sitte, N, Grune, T 2000Differential impairment of 20S and 26S proteasome activities in human hematopoietic K562 cells during oxidative stressArch Biochem Biophys3776568PubMedGoogle Scholar
  66. Reits, EA, Benham, AM, Plougastel, B, Neefjes, J, Trowsdale, J 1997Dynamics of proteasome distribution in living cellsEMBO J1660876094PubMedGoogle Scholar
  67. Rivett, AJ 1998Intracellular distribution of proteasomesCurr Opin Immunol10110114PubMedGoogle Scholar
  68. Saitoh, Y, Yokosawa, H, Ishii, S 1989Sodium Dodecyl sulfate-induced conformational and enzymatic changes of multicatalytic proteinaseBiochem Biophys Res Commun162334339PubMedGoogle Scholar
  69. Salo, DC, Lin, SW, Pacifici, RE, Davies, KJ 1988Superoxide dismutase is preferentially degraded by a proteolytic system from red blood cells following oxidative modification by hydrogen peroxideFree Radic Biol Med5335339PubMedGoogle Scholar
  70. Salo, DC, Pacifici, RE, Lin, SW, Giulivi, C, Davies, KJ 1990Superoxide dismutase undergoes proteolysis and fragmentation following oxidative modification and inactivationJ Biol Chem2651191911927PubMedGoogle Scholar
  71. Savory, PJ, Djaballah, H, Angliker, H, Shaw, E, Rivett, AJ 1993Reaction of proteasomes with peptidylchloromethanes and peptidyldiazomethanesBiochem J296601605PubMedGoogle Scholar
  72. Seeger, M, Ferrell, K, Frank, R, Dubiel, W 1997HIV-1 tat inhibits the 20S proteasome and its 11S regulator-mediated activationJ Biol Chem27281458148PubMedGoogle Scholar
  73. Shringarpure, R, Grune, T, Mehlhase, J, Davies, KJ 2003Ubiquitin conjugation is not required for the degradation of oxidized proteins by proteasomeJ Biol Chem278311318PubMedGoogle Scholar
  74. Shringarpure, R, Grune, T, Sitte, N, Davies, KJ 20004-Hydroxynonenal-modified amyloid-beta peptide ihibits the proteasome: possible importance in Alzheimer’s diseaseCell Mol Life Sci5718021809PubMedGoogle Scholar
  75. Sitte, N, Merker, K, Grune, T 1998Proteasome-dependent degradation of oxidized proteins in MRC-5 fibroblastsFEBS Lett440399402PubMedGoogle Scholar
  76. Sitte, N, Huber, M, Grune, T, Ladhoff, A, Doecke, WD, Zglinicki, T, Davies, KJA 2000aProteasome inhibition by lipofuscin/ceroid during postmitotic ageing of fibroblastsFASEB J1414901498Google Scholar
  77. Sitte, N, Merker, K, von Zglinicki, T, Davies, KJA, Grune, T 2000bProtein oxidation and degradation during cellular senescence of human BJ-fibroblasts: Part I – Effects of proliferative senescenceFASEB J1424952502Google Scholar
  78. Sitte, N, Merker, K, von Zglinicki, T, Davies, KJA, Grune, T 2000cProtein oxidation and degradation during cellular senescence of human BJ-fibroblasts: Part II – Aging of non-dividing cellsFASEB J1425032510Google Scholar
  79. Sommerburg, O, Ullrich, O, Sitte, N, von Zglinicki, D, Siems, W, Grune, T 1998Dose- and wavelength-dependent oxidation of crystallins by UV light – selective recognition and degradation by the 20S proteasomeFree Radic Biol Med2413691374PubMedGoogle Scholar
  80. von Sonntag, C 1987The chemical base of radiation oncologyTaylor & FrancisLondon930Google Scholar
  81. Spaltenstein, A, Leban, JJ, Huang, JJ, Reinhardt, KR, Viveros, OH, Sigafoos, J, Crouch, R 1996Design and synthesis of novel protease inhibitors. Tripeptide α′,β′-epoxyketones as nanomolar inactivators of the proteasomeTetrahedron Lett3713431346Google Scholar
  82. Strack, PR, Waxman, L, Fagan, JM 1996Activation of the multicatalytic endopeptidase by oxidants. Effects on enzyme structureBiochemistry3571427149PubMedGoogle Scholar
  83. Taatjes, DJ, Koch, TH 2001Nuclear targeting and retention of antracycline antitumor durgs in sensitive and resistant tumor cellsCurr Med Chem81529PubMedGoogle Scholar
  84. Tamura, T, Tamura, N, Cejka, Z, Hegerl, R, Lottspeich, F, Baumeister, W 1996Tricorn protease – the core of a modular protelytic systemScience27413851389PubMedGoogle Scholar
  85. Tanahashi, N, Yokota, K, Ahn, JY, Chung, CH, Fujiwara, T, Takahashi, E, DeMartino, GN, Slaughter, CA, Toyonaga, T, Yamamura, K, Shimbara, N, Tanaka, K 1997Molecular properties of the proteasome activator PA 28 family proteins and gamma-interferon regulationGenes Cells2195211PubMedGoogle Scholar
  86. Tanaka, K, Kasahara, M 1998The MHC Class I ligand-generationg system: roles of immunoproteasomes and the interferon-gamma-inducible proteasome activator PA28Immunol Rev163161176PubMedGoogle Scholar
  87. Tomkinson, B 1999Tripeptidyl peptidases: enzymes that countTrends Biochem Sci24355359PubMedGoogle Scholar
  88. Ullrich, O, Grune, T 2001Proteasomal degradation of oxidativly damaged endogenous histones in K562 human leukemic cellsFree Radic Biol Med31887893PubMedGoogle Scholar
  89. Ullrich, O, Reinheckel, T, Sitte, N, Grune, T 1999aDegradation of hypochlorite-damaged glucose-6-phosphate dehydrogenase by the 20S proteasomeFree Radic Biol Med27487492Google Scholar
  90. Ullrich, O, Reinheckel, T, Sitte, N, Hass, R, Grune, T, Davies, KJ 1999bPoly-ADP ribose polymerase activates nuclear proteasome to degrade oxidatively damaged histonesProc Natl Acad Sci USA9662236228Google Scholar
  91. Ullrich, O, Sitte, N, Sommerburg, O, Sandig, V, Davies, KJ, Grune, T 1999cInfluence of DNA binding on the degradation of oxidized histones by the 20S proteasomeArch Biochem Biophys362211216Google Scholar
  92. Viteri, G, Carrard, G, Birlouez-Aragon, I, Silvia, E, Friguet, B 2004Age-dependent protein modifications and declining proteasome activity in human lensArch Biochem Biophys4271393513942Google Scholar
  93. Vodenicharov, MD, Ghodgaonkar, MM, Halappanavar, SS, Shah, RG, Shah, GM 2005Mechanism of early biphasic activation of poly (ADP-ribose) polymerase-1 in response to ultraviolet B radiationJ Cell Sci118589599PubMedGoogle Scholar
  94. Voges, D, Zwickl, P, Baumeister, W 1999The 26S proteasome: a molecular machine designed for controlled proteolysisAnnu Rev Biochem6810151068PubMedGoogle Scholar
  95. Volker, C, Lupas, AN 2002Molecular evolution of proteasomesZwickl, PBaumeister, W eds. The proteasome-ubiquitin protein degradation pathwaySpringerBerlin Heidelberg122Google Scholar
  96. Walz, J, Tamura, T, Tamura, N, Grimm, R, Baumeister, W, Kloster, AJ 1997Tricorn protease exists as an icosahedral supermolecule in vivoMol Cell15965PubMedGoogle Scholar
  97. Wang, R, Chait, BT, Wolf, I, Kohanski, RA, Cardozo, C 1999Lysozyme degradation by the bovine multicatalytic proteinase complex (proteasome): evidence for a nonprocessive mode of degradationBiochemistry381457314581PubMedGoogle Scholar
  98. Wei, H, Cai, Q, Rahn, R, Zhang, X 1987Singlet oxygen involvement in ultraviolet (254 nm) radiation-induced formation of hydroxy-deoxyguanosine in DNAFree Radic Biol Med23148154Google Scholar
  99. Wenzel, T, Baumeister, W 1995Conformational constraints in protein degradation by the 20S proteasomeNature Struct Biol2199204PubMedGoogle Scholar
  100. Whitby, FG, Masters, EI, Kramer, L, Knowlton, JR, Yao, Y, Wang, CC, Hill, CP 2000Structural basis for the activation of 20S proteasomes by 11S regulatorsNature408115120PubMedGoogle Scholar
  101. Willner, C 2004An overview of the pathophysiology of neurodegenerative disordersAltern Ther Health Med102634PubMedGoogle Scholar
  102. Wold, LE, Aberle, NS,2nd, Ren, J 2005Doxorubicin induces cardiomyocyte dysfunction via a p38 MAP kinase-dependent oxidative stress mechanismCancer Detect Prev29294299PubMedGoogle Scholar
  103. Zhang, XY, Li, J, Tang, L 2005aCancer-preventive isothiocyanates: dichotomous modulators of oxidative stressFree Radic Biol Med387077Google Scholar
  104. Zhang, XY, Li, WG, WU, YJ, Gao, MT 2005bAmelioration of doxorubicin-induced myocardial oxidative stress and immunosupression by grape seed proanthocyanidins in tumor-bearing miceJ Pharm Pharmacol5710431052Google Scholar
  105. Zwickl, P 2002The 20S proteasomeZwickl, PBaumeister, W eds. The proteasome-ubiquitin protein degradation pathwaySpringerBerlin Heidelberg2342Google Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • P. Voss
    • 1
  • T. Grune
    • 1
  1. 1.Research Institute of Environmental MedicineHeinrich Heine UniversityDuesseldorfGermany

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