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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Proteomic identification of cathepsin B and nucleophosmin as novel UVA-targets in human skin fibroblasts.

Authors: Lamore, Sarah D; Qiao, Shuxi; Horn, David; Wondrak, Georg T

Published In Photochem Photobiol, (2010 Nov-Dec)

Abstract: Solar UVA exposure plays a causative role in skin photoaging and photocarcinogenesis. Here, we describe the proteomic identification of novel UVA-targets in human dermal fibroblasts following a two-dimensional-difference-gel-electrophoresis (2D-DIGE) approach. Fibroblasts were exposed to noncytotoxic doses of UVA or left untreated, and total protein extracts underwent CyDye-labeling followed by 2D-DIGE/mass-spectrometric identification of differentially expressed proteins, confirmed independently by immunodetection. The protein displaying the most pronounced UVA-induced upregulation was identified as the nucleolar protein nucleophosmin. The protein undergoing the most pronounced UVA-induced downregulation was identified as cathepsin B, a lysosomal cysteine-protease displaying loss of enzymatic activity and altered maturation after cellular UVA exposure. Extensive lysosomal accumulation of lipofuscin-like autofluorescence and osmiophilic material occurred in UVA-exposed fibroblasts as detected by confocal fluorescence microscopy and transmission electron microscopy, respectively. Array analysis indicated UVA-induced upregulation of oxidative stress response gene expression, and UVA-induced loss of cathepsin B enzymatic activity in fibroblasts was suppressed by antioxidant intervention. Pharmacological cathepsin B inhibition using CA074Me mimicked UVA-induced accumulation of lysosomal autofluorescence and deficient cathepsin B maturation. Taken together, these data support the hypothesis that cathepsin B is a crucial target of UVA-induced photo-oxidative stress causatively involved in dermal photodamage through the impairment of lysosomal removal of lipofuscin.

PubMed ID: 20946361 Exiting the NIEHS site

MeSH Terms: Acetylcysteine/pharmacology; Antioxidants/pharmacology; Cathepsin B/metabolism*; Cell Line; Dipeptides/pharmacology; Fibroblasts/metabolism; Fibroblasts/radiation effects; Gene Expression Profiling; Humans; Lipofuscin/metabolism; Lysosomes/metabolism; Nuclear Proteins/metabolism*; Oxidative Stress; Proteomics; Skin Aging/genetics; Skin Aging/physiology; Skin/metabolism*; Skin/radiation effects*; Ultraviolet Rays/adverse effects*

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