Salubrinal protects human skin fibroblasts against UVB-induced cell death by blocking endoplasmic reticulum (ER) stress and regulating calcium homeostasis
| Autor: | Shu-ying Huang, Chao Ji, Bo Yang, Bo Cheng, Jin-wen Huang |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Programmed cell death Ultraviolet Rays Photoaging Biophysics Human skin Radiation-Protective Agents CHOP Biology Biochemistry Salubrinal 03 medical and health sciences chemistry.chemical_compound medicine Homeostasis Humans Molecular Biology Cells Cultured Skin eIF2 integumentary system Cell Death Dose-Response Relationship Drug Endoplasmic reticulum Thiourea Cell Biology Fibroblasts medicine.disease Endoplasmic Reticulum Stress Skin Aging 030104 developmental biology chemistry Cinnamates Immunology Cancer research Unfolded protein response Calcium Sunscreening Agents |
| Zdroj: | Biochemical and biophysical research communications. 493(4) |
| ISSN: | 1090-2104 |
| Popis: | The role of UVB in skin photo damages has been widely reported. Overexposure to UVB will induce severe DNA damages in epidermal cells and cause most cytotoxic symptoms. In the present study, we tested the potential activity of salubrinal, a selective inhibitor of Eukaryotic Initiation Factor 2 (eIF2) -alpha phosphatase, against UV-induced skin cell damages. We first exposed human fibroblasts to UVB radiation and evaluated the cytosolic Ca2+ level as well as the induction of ER stress. We found that UVB radiation induced the depletion of ER Ca2+ and increased the expression of ER stress marker including phosphorylated PERK, CHOP, and phosphorylated IRE1α. We then determined the effects of salubrinal in skin cell death induced by UVB radiation. We observed that cells pre-treated with salubrinal had a higher survival rate compared to cells treated with UVB alone. Pre-treatment with salubrinal successfully re-established the ER function and Ca2+ homeostasis. Our results suggest that salubrinal can be a potential therapeutic agents used in preventing photoaging and photo damages. |
| Databáze: | OpenAIRE |
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