Regulation of cysteine cathepsin expression by oxidative stress in the retinal pigment epithelium/choroid of the mouse

Parvaneh Alizadeh, Zeljka McBride, Sharon L. Oltjen, Leonard M Hjelmeland

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Cystatin C is the major inhibitor of the cysteine cathepsins. Polymorphisms in the cystatin C gene have recently been associated with the risk of developing Age-related Macular Degeneration (AMD). Oxidative stress is also thought to play a key role in the pathogenesis of AMD. We surveyed the retinal pigment epithelium (RPE) and choroid of the C57BL/6J mouse for the expression of the cysteine cathepsins under normoxic and hyperoxic (75% O2) conditions. Microarray analysis of RPE/choroid mRNA revealed the expression of cathepsins B and L, as well as cystatin C under all experimental conditions. The microarray results were confirmed by real-time quantitative polymerase chain reaction (PCR). Localization of the mRNA species for cystatin C and cathepsin B, as well as, localization of protein species for cystatin C, cathepsins B and L were performed to evaluate the tissue distribution of these species. Our results indicate that cystatin C is largely synthesized in the RPE and secreted from the basal side. Cathepsin B is the major cysteine protease in the RPE and choroid. The expression of all mRNAs and proteins was elevated by exposure to oxidative stress.

Original languageEnglish (US)
Pages (from-to)679-687
Number of pages9
JournalExperimental Eye Research
Volume83
Issue number3
DOIs
StatePublished - Sep 2006

Keywords

  • cathepsins
  • cystatins
  • mouse
  • oxidative stress
  • retinal pigment epithelium

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

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