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.

journal_name

J Neurochem

authors

Hussong SA,Kapphahn RJ,Phillips SL,Maldonado M,Ferrington DA

doi

10.1111/j.1471-4159.2010.06688.x

subject

Has Abstract

pub_date

2010-06-01 00:00:00

pages

1481-90

issue

6

eissn

0022-3042

issn

1471-4159

pii

JNC6688

journal_volume

113

pub_type

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