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PMID: 18346202 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Immunoproteasome responds to injury in the retina and brain.

Journal of neurochemistry ·Vol. 106 ·No. 1 ·2008-07-00 ·Pages 158-69

Ferrington DA, Hussong SA, Roehrich H, Kapphahn RJ, Kavanaugh SM, Heuss ND, Gregerson DS

Abstract

It is well known that immunoproteasome generates peptides for MHC Class I occupancy and recognition by cytotoxic T lymphocytes (CTL). The present study focused on evidence for alternative roles for immunoproteasome. Retina and brain were analyzed for expression of immunoproteasome subunits using immunohistochemistry and western blotting under normal conditions and after injury/stress induced by CTL attack on glia (brain) or neurons (retina). Normal retina expressed substantial levels of immunoproteasome in glia, neurons, and retinal pigment epithelium. The basal level of immunoproteasome in retina was two-fold higher than in brain; CTL-induced retinal injury further up-regulated immunoproteasome expression. Immunoproteasome up-regulation was also observed in injured brain and corresponded with expression in Purkinje cells, microglia, astrocytes, and oligodendrocytes. These results suggest that the normal environment of the retina is sufficiently challenging to require on-going expression of immunoproteasome. Further, immunoproteasome up-regulation with retinal and brain injury implies a role in neuronal protection and/or repair of damage.

MeSH Terms
Animals Brain/immunology,physiopathology Cell Communication/immunology Encephalitis/immunology,physiopathology Mice Mice, Transgenic Nerve Degeneration/immunology,physiopathology Nerve Regeneration/immunology Neuroglia/immunology,pathology Neuronal Plasticity/immunology Neurons/immunology,pathology Pigment Epithelium of Eye/immunology,physiopathology Proteasome Endopeptidase Complex/immunology Protein Subunits/immunology Recovery of Function/immunology Retina/immunology,physiopathology Retinitis/immunology,physiopathology T-Lymphocytes, Cytotoxic/immunology Up-Regulation/immunology
Chemicals
Protein Subunits Proteasome Endopeptidase Complex
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Ferrington Deborah A
Department of Ophthalmology, University of Minnesota, Minneapolis, Minnesota, USA. [email protected]
Hussong Stacy A
Roehrich Heidi
Kapphahn Rebecca J
Kavanaugh Shannon M
Heuss Neal D
Gregerson Dale S
References (51)
51 references, click to expand
  1. Altered proteasome function and subunit composition in aged muscle.
    Arch Biochem Biophys. 2004 Jan 1;421(1):67-76 PMID: 14678786
  2. DNA sequence, chromosomal localization, and tissue expression of the mouse proteasome subunit lmp10 (Psmb10) gene.
    Genomics. 1997 Nov 1;45(3):618-22 PMID: 9367687
  3. Autocatalytic subunit processing couples active site formation in the 20S proteasome to completion of assembly.
    Cell. 1996 Sep 20;86(6):961-72 PMID: 8808631
  4. Biochemical analysis of proteasomes from mouse microglia: induction of immunoproteasomes by interferon-gamma and lipopolysaccharide.
    Glia. 2000 Feb 15;29(4):355-65 PMID: 10652445
  5. Bystander killing of neurons by cytotoxic T cells specific for a glial antigen.
    Glia. 2006 Apr 1;53(5):457-66 PMID: 16355370
  6. RPE cells resist bystander killing by CTLs, but are highly susceptible to antigen-dependent CTL killing.
    Invest Ophthalmol Vis Sci. 2006 Dec;47(12):5385-94 PMID: 17122128
  7. Genomic organization and tissue expression of the mouse proteasome gene Lmp-7.
    Immunogenetics. 1993;38(6):400-7 PMID: 8406612
  8. Indicator expression directed by regulatory sequences of the glial fibrillary acidic protein (GFAP) gene: in vivo comparison of distinct GFAP-lacZ transgenes.
    Glia. 1995 Mar;13(3):174-84 PMID: 7782103
  9. Activity level controls postsynaptic composition and signaling via the ubiquitin-proteasome system.
    Nat Neurosci. 2003 Mar;6(3):231-42 PMID: 12577062
  10. LMP2 knock-out mice have reduced proteasome activities and increased levels of oxidatively damaged proteins.
    Antioxid Redox Signal. 2006 Jan-Feb;8(1-2):130-5 PMID: 16487046
  11. NOD mice are defective in proteasome production and activation of NF-kappaB.
    Mol Cell Biol. 1999 Dec;19(12):8646-59 PMID: 10567588
  12. Proteasome function and protein oxidation in the aged retina.
    Exp Eye Res. 2002 Sep;75(3):271-84 PMID: 12384090
  13. Failure of memory (CD44 high) CD4 T cells to recognize their target antigen in retina.
    J Neuroimmunol. 2001 Nov 1;120(1-2):34-41 PMID: 11694317
  14. Activity-dependent dynamics and sequestration of proteasomes in dendritic spines.
    Nature. 2006 Jun 29;441(7097):1144-8 PMID: 16810255
  15. Distribution and phenotype of dendritic cells and resident tissue macrophages in the dura mater, leptomeninges, and choroid plexus of the rat brain as demonstrated in wholemount preparations.
    J Comp Neurol. 1999 Mar 22;405(4):553-62 PMID: 10098945
  16. CD45-positive cells of the retina and their responsiveness to in vivo and in vitro treatment with IFN-gamma or anti-CD40.
    Invest Ophthalmol Vis Sci. 2003 Jul;44(7):3083-93 PMID: 12824255
  17. The importance of the proteasome and subsequent proteolytic steps in the generation of antigenic peptides.
    Mol Immunol. 2002 Oct;39(3-4):147-64 PMID: 12200047
  18. Transformation of the proteasome with age-related macular degeneration.
    FEBS Lett. 2007 Mar 6;581(5):885-90 PMID: 17289037
  19. Immunoproteasome and LMP2 polymorphism in aged and Alzheimer's disease brains.
    Neurobiol Aging. 2006 Jan;27(1):54-66 PMID: 16298241
  20. Resting CD8 T cells recognize beta-galactosidase expressed in the immune-privileged retina and mediate autoimmune disease when activated.
    Immunology. 2003 Nov;110(3):386-96 PMID: 14632667
  21. Retinal proteins modified by 4-hydroxynonenal: identification of molecular targets.
    Exp Eye Res. 2006 Jul;83(1):165-75 PMID: 16530755
  22. Different requirements for signal transducer and activator of transcription 1alpha and interferon regulatory factor 1 in the regulation of low molecular mass polypeptide 2 and transporter associated with antigen processing 1 gene expression.
    J Biol Chem. 1998 Jun 26;273(26):16177-83 PMID: 9632673
  23. Structure and functions of the 20S and 26S proteasomes.
    Annu Rev Biochem. 1996;65:801-47 PMID: 8811196
  24. The antigen-presenting activity of fresh, adult parenchymal microglia and perivascular cells from retina.
    J Immunol. 2004 Jun 1;172(11):6587-97 PMID: 15153473
  25. Activation of microglia and chemokines in light-induced retinal degeneration.
    Mol Vis. 2005 Oct 27;11:887-95 PMID: 16270028
  26. Tissue distribution of constitutive proteasomes, immunoproteasomes, and PA28 in rats.
    Biochem Biophys Res Commun. 2000 Oct 22;277(2):348-54 PMID: 11032729
  27. cDNA cloning and interferon gamma down-regulation of proteasomal subunits X and Y.
    Science. 1994 Aug 26;265(5176):1231-4 PMID: 8066462
  28. Proteolytic processing of ovalbumin and beta-galactosidase by the proteasome to a yield antigenic peptides.
    J Immunol. 1994 Apr 15;152(8):3884-94 PMID: 8144958
  29. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules.
    Cell. 1994 Sep 9;78(5):761-71 PMID: 8087844
  30. Regulation of immunoproteasome subunit expression in vivo following pathogenic fungal infection.
    J Immunol. 2002 Sep 15;169(6):3046-52 PMID: 12218120
  31. Spontaneous induction of immunoregulation by an endogenous retinal antigen.
    Invest Ophthalmol Vis Sci. 2002 Sep;43(9):2984-91 PMID: 12202519
  32. The proximal promoter of the mouse arrestin gene directs gene expression in photoreceptor cells and contains an evolutionarily conserved retinal factor-binding site.
    Mol Cell Biol. 1993 Jul;13(7):4400-8 PMID: 8321239
  33. The concept of microglia in relation to central nervous system disease and regeneration.
    Prog Neurobiol. 1996 Mar-Apr;48(4-5):441-60 PMID: 8804116
  34. Age-dependent inhibition of proteasome chymotrypsin-like activity in the retina.
    Exp Eye Res. 2007 Apr;84(4):646-54 PMID: 17258201
  35. Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expression.
    Neuron. 2003 Oct 30;40(3):595-607 PMID: 14642282
  36. Regulation of the glutamate transporter EAAT1 by the ubiquitin ligase Nedd4-2 and the serum and glucocorticoid-inducible kinase isoforms SGK1/3 and protein kinase B.
    J Neurochem. 2003 Sep;86(5):1181-8 PMID: 12911626
  37. Retinal expression of a neo-self antigen, beta-galactosidase, is not tolerogenic and creates a target for autoimmune uveoretinitis.
    J Immunol. 1999 Jul 15;163(2):1073-80 PMID: 10395707
  38. Expression of glial fibrillary acidic protein and glutamine synthetase by Müller cells after optic nerve damage and intravitreal application of brain-derived neurotrophic factor.
    Glia. 2002 Apr 15;38(2):115-25 PMID: 11948805
  39. Enhanced induction of the immunoproteasome by interferon gamma in neurons expressing mutant Huntingtin.
    Neurotox Res. 2004;6(6):463-8 PMID: 15658001
  40. Selected contribution: Association of gender-related LMP2 inactivation with autoimmune pathogenesis.
    J Appl Physiol (1985). 2001 Dec;91(6):2804-15 PMID: 11717249
  41. Different death stimuli evoke apoptosis via multiple pathways in retinal pigment epithelial cells.
    Exp Eye Res. 2006 Sep;83(3):638-50 PMID: 16682026
  42. Unilateral optic nerve crush induces bilateral retinal glial cell proliferation.
    Eur J Neurosci. 2005 Apr;21(8):2305-9 PMID: 15869529
  43. Regulation of the neuronal proteasome by Zif268 (Egr1).
    J Neurosci. 2006 Feb 1;26(5):1624-34 PMID: 16452686
  44. Identification of MECL-1 (LMP-10) as the third IFN-gamma-inducible proteasome subunit.
    J Immunol. 1996 Apr 1;156(7):2361-4 PMID: 8786291
  45. Immunoproteasome expression in a nonimmune tissue, the ocular lens.
    Arch Biochem Biophys. 2002 Sep 15;405(2):147-53 PMID: 12220526
  46. Intermediate-type 20 S proteasomes in HeLa cells: "asymmetric" subunit composition, diversity and adaptation.
    J Mol Biol. 2007 Oct 12;373(1):1-10 PMID: 17804016
  47. Role of the proteasome in protein oxidation and neural viability following low-level oxidative stress.
    FEBS Lett. 2003 Jul 10;546(2-3):228-32 PMID: 12832045
  48. Alterations of cerebral cortex and hippocampal proteasome subunit expression and function in a traumatic brain injury rat model.
    J Neurochem. 2008 Jan;104(2):353-63 PMID: 17944870
  49. Nucleotide sequence analysis of the approximately 35-kb segment containing interferon-gamma-inducible mouse proteasome activator genes.
    Immunogenetics. 2001 Mar;53(2):119-29 PMID: 11345588
  50. Altered proteasome structure, function, and oxidation in aged muscle.
    FASEB J. 2005 Apr;19(6):644-6 PMID: 15677694
  51. Different proteasome subtypes in a single tissue exhibit different enzymatic properties.
    J Mol Biol. 2000 Nov 10;303(5):643-53 PMID: 11061965
Article Info
Journal
Journal of neurochemistry
Abbr.
J Neurochem
ISSN
1471-4159
Published
2008-07-00
Epub
2008-00-01
Pages
158-69
Language
English
Region
England
NLM ID
2985190R
PMCID
PMC4401486
Subset
IM
Grants
NIA NIH HHS · R21 AG032391 · United States
NEI NIH HHS · EY011542 · United States
NEI NIH HHS · P30-EY11374 · United States
NEI NIH HHS · P30 EY011374 · United States
NEI NIH HHS · R01 EY013623 · United States
NEI NIH HHS · R01 EY011542 · United States
NEI NIH HHS · EY013623 · United States
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