Evidence map›Paper›PMID 21773629›Full record

ArticlePhotochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology2012

Autophagic-lysosomal dysregulation downstream of cathepsin B inactivation in human skin fibroblasts exposed to UVA.

Sarah D Lamore, Georg T Wondrak

Abstract read
In one paragraph

Article in Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.0field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 51 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Cathepsins in neuronal plasticity.Neural regeneration research · 2021
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Autophagy in UV Damage Response.Photochemistry and photobiology · 2017
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Sarah D LamoreDepartment of Pharmacology and Toxicology, College of Pharmacy & University of Arizona, Arizona Cancer Center, 1515 North Campbell Avenue, Tucson, AZ 85724, USA.
Georg T Wondrak
University of Arizona · US

Funding

VITAMIN AP30CA023074 · NCI · UNIVERSITY OF ARIZONA · PI Dan Theodorescu · 1985 to 2026
$110.2M
SOUTHWEST ENVIRONMENTAL HEALTH SCIENCES CENTERP30ES006694 · NIEHS · UNIVERSITY OF ARIZONA · PI DEAN BILLHEIMER · 1994 to 2026
$36.7M
Training in Environmental Toxicology of Human DiseaseT32ES007091 · NIEHS · UNIVERSITY OF ARIZONA · PI Nathan J Cherrington · 1985 to 2026
$10.7M
Targeting Glycolytic Control of Melanoma Cell SurvivalR01CA122484 · NCI · UNIVERSITY OF ARIZONA · PI WONDRAK, GEORG T · 2007 to 2011
$1.3M
NCI NIH HHS CA023074NCI NIH HHS P30 CA023074NCI NIH HHS R01 CA122484NCI NIH HHS R01CA122484NIEHS NIH HHS ES006694NIEHS NIH HHS ES007091NIEHS NIH HHS P30 ES006694NIEHS NIH HHS T32 ES007091
6 · The paper itself

Abstract

Recently, using 2D-DIGE proteomics we have identified cathepsin B as a novel target of UVA in human Hs27 skin fibroblasts. In response to chronic exposure to noncytotoxic doses of UVA (9.9 J cm(-2), twice a week, 3 weeks), photooxidative impairment of cathepsin B enzymatic activity occurred with accumulation of autofluorescent aggregates colocalizing with lysosomes, an effect mimicked by pharmacological antagonism of cathepsin B using the selective inhibitor CA074Me. Here, we have further explored the mechanistic involvement of cathepsin B inactivation in UVA-induced autophagic-lysosomal alterations using autophagy-directed PCR expression array analysis as a discovery tool. Consistent with lysosomal expansion, UVA upregulated cellular protein levels of the lysosomal marker glycoprotein Lamp-1, and increased levels of the lipidated autophagosomal membrane constituent LC3-II were detected. UVA did not alter expression of beclin 1 (BECN1), an essential factor for initiation of autophagy, but upregulation of p62 (sequestosome 1, SQSTM1), a selective autophagy substrate, and α-synuclein (SNCA), an autophagic protein substrate and aggresome component, was observed at the mRNA and protein level. Moreover, UVA downregulated transglutaminase-2 (TGM2), an essential enzyme involved in autophagolysosome maturation. Strikingly, UVA effects on Lamp-1, LC3-II, beclin 1, p62, α-synuclein, and transglutaminase-2 were mimicked by CA074Me treatment. Taken together, our data suggest that UVA-induced autophagic-lysosomal alterations occur as a consequence of impaired autophagic flux downstream of cathepsin B inactivation, a novel molecular mechanism potentially involved in UVA-induced skin photodamage.

Indexed as

AutophagyUltraviolet RaysCathepsin BElectrophoresis, Polyacrylamide GelFibroblastsFlow CytometryHumansLysosomesMicroscopy, ConfocalMicroscopy, Electron, TransmissionPolymerase Chain ReactionSkinCathepsin B

Identifiers

PMID21773629
PMCPMC4089038
OpenAlexW2139354073

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.