Cited by 5Protease and Inhibitor MechanismsRetinal Development and DisordersRetinal Diseases and Treatments

Controlled production of active Cathepsin D in Retinal Pigment Epithelial cells following adenovirus-mediated gene delivery

Open access
Lai, Chooi-May, Robertson, Terry, Papadimitriou, John, Shen, Wei-Yong, Daw, Natalie, Constable, Ian J., Rakoczy, Piroska E.·2000·Molecular Therapy

Abstract

The transduction of a low cathepsin D-producing retinal pigment epithelial cell line with a recombinant adenovirus, Ad.proCatD, carrying a viral promoter and the precursor form of the lysosomal enzyme cathepsin D, procathepsin D, led to the upregulation of proCatD expression. However, the resultant aspartic protease activity did not exceed that observed in normal primary human retinal pigment epithelial cells. Following the injection of Ad. proCatD into rat eyes, immunohistochemistry and Western blot analysis localized the expression of procathepsin D to the retinal pigment epithelial cell layer and to the sclera/choroid/retinal epithelial cell layers, respectively. This upregulation of procathepsin D expression was accompanied by a limited increase in aspartic protease activity. The injected eyes did not demonstrate any of the retinal changes that have been associated with the overproduction and secretion of active cathepsin D. Immunoelectronmicroscopy of Ad.proCatD-transduced retinal pigment epithelial cells demonstrated the presence of cathepsin D not only in cytoplasmic vesicles and lysosomes but also in the nucleoli and, less strongly, elsewhere in euchromatic regions of some 10% of cells. In spite of the upregulated expression of procathepsin D, the production of active cathepsin D in Ad.proCatD-transduced retinal pigment epithelial cells was strictly controlled. It is proposed that active cathepsin D production is controlled at the point of posttranslational modification by an intranuclear feedback mechanism initiated by the relative excess of procathepsin D in Ad. proCatD-transduced retinal pigment epithelial cells.

Integrity signals

Registry

Crossref · 10.1006/mthe.2000.0195

Cites

36 of 36 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Cathepsin D activity is strictly regulated by post-translational modifications.

    “Perhaps, unsurprisingly, there is strict regulation of cathepsin D activity using post-translational modifications (Lai et al., 2000).”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Lai et al., 2000

Cites

Flagged first, then by citations

1 of the 37 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Lai, C.-M., Robertson, T., Papadimitriou, J., Shen, W.-Y., Daw, N., Constable, I. J., & Rakoczy, P. E.
Affiliations
  • Lions Eye Institute (AU)
  • The University of Western Australia (AU)
Corresponding author
Rakoczy, Piroska E.
Venue
Molecular Therapy
Publisher
Elsevier BV
Published
2000-11
Volume
2
Issue
5
Pages
476-484
ISSN
1525-0016 (ISSN-L)
OpenAlex
W2025977442
Cited by
5
References
37
Citations by year
2020: 2 · 2018: 1 · 2015: 1
FWCI
0.00
Type
journal article
Language
en
Open access
Locations
  • Molecular Therapy (publishedVersion, cc-by-nc-nd)
  • UWA Profiles and Research Repository (UWA) (publishedVersion, other-oa)
  • PubMed (publishedVersion)
Topics
  • 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
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Keywords
cathepsin D, retinal pigment epithelial cells, adenoviral gene transfer, procathepsin D, post-translational modification, lysosomal enzymes, nucleolar localization, ocular gene therapy
MeSH terms
Adenoviridae, Animals, Cathepsin D, Cell Line, Enzyme Precursors, Epithelial Cells, Genetic Vectors, Humans, Injections, Phagocytosis, Pigment Epithelium of Eye, Protein Processing, Post-Translational, Transduction, Genetic, Microscopy, Immunoelectron, Transgenes, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review