ALA-PDT elicits oxidative damage and apoptosis in UVB-induced premature senescence of human skin fibroblasts
Abstract
Background 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been used for the treatment of skin photoaging. It can significantly improve the appearance of fine lines, dotted pigmentation, and roughness of photoaged skin. However, the mechanisms by which ALA-PDT yields rejuvenating effects on photoaged skin have not been well elucidated. Thus, in this study we explored the effects of ALA-PDT in photoaged fibroblasts. Methods We established a stress-induced premature senescence (SIPS) model by repeated exposures of human dermal fibroblasts (HDFs) to ultraviolet B (UVB) irradiation. Cells were irradiated by red light laser at 635nm wavelength (50mW/cm(2)). Intracellular protoporphyrin IX (PpIX) was detected by confocal microscopy. Intracellular reactive oxygen species (ROS) level and mitochondrial membrane potential (MMP) change were detected by fluorescence microscopy and flow cytometry. Morphological changes were observed by optical microscopy. Proliferative activity was measured by a cell counting kit-8 (CCK-8). Cell apoptosis was detected by fluorescence microscopy using Hoechst staining and flow cytometry using annexin V/propidium Iodide double staining. Results Intracellular PpIX fluorescence in UVB-induced premature senescent HDFs (UVB-SIPS-HDFs) reached the highest intensity after incubation with 1.00mmol/L ALA for 6h (P<0.05). Compared with control group, intracellular ROS level, MMP, and apoptotic rate were increased (P<0.05) and proliferative activity was decreased (P<0.05) in UVB-SIPS-HDFs treated with ALA-PDT, which were positively correlated to ALA incubation time and red light laser dose. Conclusion Our study demonstrated that ALA-PDT elicits oxidative damage and apoptosis in photoaged fibroblasts in vitro, which may be the basis for the rejuvenating effects on photoaged skin.
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Loss of mitochondrial membrane potential induces apoptotic cell death by activating the caspase-9-mediated mitochondrial apoptotic pathway.
“Consequently, the loss of mitochondrial membrane potential induces apoptotic cell death by activating the caspase-9-mediated mitochondrial apoptotic pathway, as shown in multiple studies with various cell lines [25,26,27,28].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [28]
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- Authors
- Zhou, B.-R., Zhang, L.-C., Permatasari, F., Liu, J., Xu, Y., & Luo, D.
- Affiliations
- Jiangsu Province Hospital (CN)
- Corresponding author
- Luo, Dan
- Venue
- Photodiagnosis and Photodynamic Therapy
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 14
- Pages
- 47-56
- ISSN
- 1572-1000 (ISSN-L)
- OpenAlex
- W2288050073
- Cited by
- 23
- References
- 22
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 4 · 2020: 1 · 2019: 5 · 2018: 2 · 2017: 3 · 2016: 2
- FWCI
- 3.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Photodiagnosis and Photodynamic Therapy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fonds National de la Recherche Luxembourg
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
- Keywords
- 5-aminolevulinic acid photodynamic therapy, photoaging, stress-induced premature senescence, human dermal fibroblasts, UVB irradiation, oxidative damage, apoptosis, reactive oxygen species, mitochondrial membrane potential, protoporphyrin IX, skin rejuvenation
- MeSH terms
- Aminolevulinic Acid, Fibroblasts, Flow Cytometry, Humans, Microscopy, Fluorescence, Photochemotherapy, Skin, Ultraviolet Rays, Cellular Senescence, Apoptosis, Reactive Oxygen Species, Microscopy, Confocal
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