Regulation of cysteine cathepsin expression by oxidative stress in the retinal pigment epithelium/choroid of the mouse
Open accessAbstract
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% O(2)) 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.
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Cathepsin B is identified in mouse, bovine, and human RPE, with some variation in protein expression at least in RPE from individual rats.
“Cathepsin B has also been identified in the mouse (Alizadeh et al., 2006; Ahuja et al., 2008), bovine (Fröhlich and Klessen, 2001), and human (Hoppe et al., 2004b) RPE, although there appears to be some variation in the level of protein expression, at least in RPE from individual rats (Wassélius et al., 2003).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Alizadeh et al., 2006
Cathepsin L is detected at the transcript level in mouse RPE and can be upregulated in response to hyperoxia.
“Cathepsin L has been detected at the transcript level in mouse RPE and can be upregulated in response to hyperoxia (Alizadeh et al., 2006).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Alizadeh et al., 2006
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The cell biology of the retinal pigment epithelium
Lakkaraju, A., Umapathy, A., Tan, L. X., Daniele, L., Philp, N. J., Boesze-Battaglia, K., & Williams, D. S. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100846 · Cited by 422 · see citing works
- Authors
- Alizadeh, P., Smit-McBride, Z., Oltjen, S. L., & Hjelmeland, L. M.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Hjelmeland, Leonard M.
- ORCID
- Oltjen, Sharon L.
- Venue
- Experimental Eye Research
- Publisher
- Elsevier BV
- Published
- 2006-09
- Volume
- 83
- Issue
- 3
- Pages
- 679-687
- ISSN
- 0014-4835 (ISSN-L)
- PMC
- PMC1661778
- OpenAlex
- W1979551605
- Cited by
- 23
- References
- 26
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 1 · 2014: 2 · 2013: 2
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Eye Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Research to Prevent Blindness
- National Institutes of Health
- National Eye Institute (R01EY006473, P30-EY-12576, R01EY06473, P30EY012576)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- cystatin C, cysteine cathepsins, cathepsin B, cathepsin L, oxidative stress, hyperoxia, retinal pigment epithelium, choroid, age-related macular degeneration, gene expression regulation, protein secretion, C57BL/6J mice
- MeSH terms
- Animals, Cathepsin B, Cathepsins, Choroid, Immunohistochemistry, Pigment Epithelium of Eye, RNA, Messenger, Gene Expression, Cystatins, Oxidative Stress, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Mice, Cystatin C
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