ArticlePhotochemistry and photobiology
Proteomic identification of cathepsin B and nucleophosmin as novel UVA-targets in human skin fibroblasts.
Article in Photochemistry and photobiology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 35 citations in OpenAlex.
- Skin Ageing: A Progressive, Multi-Factorial Condition Demanding an Integrated, Multilayer-Targeted Remedy.Clinical, cosmetic and investigational dermatology · 2023Review
- Modulation of autophagy, apoptosis and oxidative stress: a clue for repurposing metformin in photoaging.Inflammopharmacology · 2022Article
- Counteracting the Ramifications of UVB Irradiation and Photoaging withMolecules (Basel, Switzerland) · 2021Article
- Parkinson's Disease Skin Fibroblasts Display Signature Alterations in Growth, Redox Homeostasis, Mitochondrial Function, and Autophagy.Frontiers in neuroscience · 2017Article
- Influence of a pre-stimulation with chronic low-dose UVB on stress response mechanisms in human skin fibroblasts.PloS one · 2017Article
- Systemic administration of the apocarotenoid bixin protects skin against solar UV-induced damage through activation of NRF2.Free radical biology & medicine · 2015Article
- The Tryptophan-Derived Endogenous Aryl Hydrocarbon Receptor Ligand 6-Formylindolo[3,2-b]Carbazole Is a Nanomolar UVA Photosensitizer in Epidermal Keratinocytes.The Journal of investigative dermatology · 2015Article
- Article
- UVA causes dual inactivation of cathepsin B and L underlying lysosomal dysfunction in human dermal fibroblasts.Journal of photochemistry and photobiology. B, Biology · 2013Article
- The Nrf2-inducers tanshinone I and dihydrotanshinone protect human skin cells and reconstructed human skin against solar simulated UV.Redox biology · 2013Article
- The redox antimalarial dihydroartemisinin targets human metastatic melanoma cells but not primary melanocytes with induction of NOXA-dependent apoptosis.Investigational new drugs · 2012Article
- Autophagic-lysosomal dysregulation downstream of cathepsin B inactivation in human skin fibroblasts exposed to UVA.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2012Article
- Zinc pyrithione impairs zinc homeostasis and upregulates stress response gene expression in reconstructed human epidermis.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2011Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
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.
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