Immunoproteasome deficiency alters retinal proteasome's response to stress

Stacy A. Hussong, Becky Kapphahn, Stacia L. Phillips, Marcela Maldonado, Deborah A Ferrington

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Our previous work demonstrated that immunoproteasome is up-regulated in the retina and brain in response to injury that does not involve an inflammatory response (J. Neurochem. 2008; 106:158). These results suggest additional non-immune functions for the immunoproteasome in the cellular stress response pathway. The present study further investigates the potential involvement of the immunoproteasome in responding to the chronic stress of aging or oxidant exposure in the retina and cultured retinal pigment epithelial (RPE) cells from knock-out mice missing either one (lmp7-/-) or two (lmp7 -/-/mecl-1-/-) immunoproteasome subunits. We show that aging and chronic oxidative stress up-regulates immunoproteasome in the retina and RPE from wild-type mice. No up-regulation of LMP2 was observed in retinas or RPE lacking MECL-1 and/or LMP7, suggesting that the full complement of immunoproteasome subunits is required to achieve maximal up-regulation in response to stress. We also show that RPE deficient in immunoproteasome are more susceptible to oxidation-induced cell death, supporting a role for immunoproteasome in protecting from oxidative stress. These results provide key mechanistic insight into novel aspects of proteasome biology and are an important first step in identifying alternative roles for retinal immunoproteasome that are unrelated to its role in the immune response.

Original languageEnglish (US)
Pages (from-to)1481-1490
Number of pages10
JournalJournal of Neurochemistry
Volume113
Issue number6
DOIs
StatePublished - Jun 1 2010

Fingerprint

Retinal Pigments
Proteasome Endopeptidase Complex
Retina
Oxidative stress
Up-Regulation
Oxidative Stress
Aging of materials
Cell death
Oxidants
Knockout Mice
Brain
Cell Death
Epithelial Cells
Oxidation
Wounds and Injuries

Keywords

  • Age
  • Immunoproteasome
  • Lmp7
  • Lmp7/mecl-1
  • Retina
  • Stress

Cite this

Immunoproteasome deficiency alters retinal proteasome's response to stress. / Hussong, Stacy A.; Kapphahn, Becky; Phillips, Stacia L.; Maldonado, Marcela; Ferrington, Deborah A.

In: Journal of Neurochemistry, Vol. 113, No. 6, 01.06.2010, p. 1481-1490.

Research output: Contribution to journalArticle

Hussong, Stacy A. ; Kapphahn, Becky ; Phillips, Stacia L. ; Maldonado, Marcela ; Ferrington, Deborah A. / Immunoproteasome deficiency alters retinal proteasome's response to stress. In: Journal of Neurochemistry. 2010 ; Vol. 113, No. 6. pp. 1481-1490.
@article{c7fc12837c2b44df980294c33ea712a2,
title = "Immunoproteasome deficiency alters retinal proteasome's response to stress",
abstract = "Our previous work demonstrated that immunoproteasome is up-regulated in the retina and brain in response to injury that does not involve an inflammatory response (J. Neurochem. 2008; 106:158). These results suggest additional non-immune functions for the immunoproteasome in the cellular stress response pathway. The present study further investigates the potential involvement of the immunoproteasome in responding to the chronic stress of aging or oxidant exposure in the retina and cultured retinal pigment epithelial (RPE) cells from knock-out mice missing either one (lmp7-/-) or two (lmp7 -/-/mecl-1-/-) immunoproteasome subunits. We show that aging and chronic oxidative stress up-regulates immunoproteasome in the retina and RPE from wild-type mice. No up-regulation of LMP2 was observed in retinas or RPE lacking MECL-1 and/or LMP7, suggesting that the full complement of immunoproteasome subunits is required to achieve maximal up-regulation in response to stress. We also show that RPE deficient in immunoproteasome are more susceptible to oxidation-induced cell death, supporting a role for immunoproteasome in protecting from oxidative stress. These results provide key mechanistic insight into novel aspects of proteasome biology and are an important first step in identifying alternative roles for retinal immunoproteasome that are unrelated to its role in the immune response.",
keywords = "Age, Immunoproteasome, Lmp7, Lmp7/mecl-1, Retina, Stress",
author = "Hussong, {Stacy A.} and Becky Kapphahn and Phillips, {Stacia L.} and Marcela Maldonado and Ferrington, {Deborah A}",
year = "2010",
month = "6",
day = "1",
doi = "10.1111/j.1471-4159.2010.06688.x",
language = "English (US)",
volume = "113",
pages = "1481--1490",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Immunoproteasome deficiency alters retinal proteasome's response to stress

AU - Hussong, Stacy A.

AU - Kapphahn, Becky

AU - Phillips, Stacia L.

AU - Maldonado, Marcela

AU - Ferrington, Deborah A

PY - 2010/6/1

Y1 - 2010/6/1

N2 - Our previous work demonstrated that immunoproteasome is up-regulated in the retina and brain in response to injury that does not involve an inflammatory response (J. Neurochem. 2008; 106:158). These results suggest additional non-immune functions for the immunoproteasome in the cellular stress response pathway. The present study further investigates the potential involvement of the immunoproteasome in responding to the chronic stress of aging or oxidant exposure in the retina and cultured retinal pigment epithelial (RPE) cells from knock-out mice missing either one (lmp7-/-) or two (lmp7 -/-/mecl-1-/-) immunoproteasome subunits. We show that aging and chronic oxidative stress up-regulates immunoproteasome in the retina and RPE from wild-type mice. No up-regulation of LMP2 was observed in retinas or RPE lacking MECL-1 and/or LMP7, suggesting that the full complement of immunoproteasome subunits is required to achieve maximal up-regulation in response to stress. We also show that RPE deficient in immunoproteasome are more susceptible to oxidation-induced cell death, supporting a role for immunoproteasome in protecting from oxidative stress. These results provide key mechanistic insight into novel aspects of proteasome biology and are an important first step in identifying alternative roles for retinal immunoproteasome that are unrelated to its role in the immune response.

AB - Our previous work demonstrated that immunoproteasome is up-regulated in the retina and brain in response to injury that does not involve an inflammatory response (J. Neurochem. 2008; 106:158). These results suggest additional non-immune functions for the immunoproteasome in the cellular stress response pathway. The present study further investigates the potential involvement of the immunoproteasome in responding to the chronic stress of aging or oxidant exposure in the retina and cultured retinal pigment epithelial (RPE) cells from knock-out mice missing either one (lmp7-/-) or two (lmp7 -/-/mecl-1-/-) immunoproteasome subunits. We show that aging and chronic oxidative stress up-regulates immunoproteasome in the retina and RPE from wild-type mice. No up-regulation of LMP2 was observed in retinas or RPE lacking MECL-1 and/or LMP7, suggesting that the full complement of immunoproteasome subunits is required to achieve maximal up-regulation in response to stress. We also show that RPE deficient in immunoproteasome are more susceptible to oxidation-induced cell death, supporting a role for immunoproteasome in protecting from oxidative stress. These results provide key mechanistic insight into novel aspects of proteasome biology and are an important first step in identifying alternative roles for retinal immunoproteasome that are unrelated to its role in the immune response.

KW - Age

KW - Immunoproteasome

KW - Lmp7

KW - Lmp7/mecl-1

KW - Retina

KW - Stress

UR - http://www.scopus.com/inward/record.url?scp=77953101405&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953101405&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.2010.06688.x

DO - 10.1111/j.1471-4159.2010.06688.x

M3 - Article

C2 - 20345760

AN - SCOPUS:77953101405

VL - 113

SP - 1481

EP - 1490

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 6

ER -