Oxidative stress mediated Ca(2+) release manifests endoplasmic reticulum stress leading to unfolded protein response in UV-B irradiated human skin cells
| Autor: | Quadri Afnan, Rather A. Rafiq, Love Sharma, Sheikh A. Tasduq, Peerzada Kaiser, Mufti R. Farrukh, Shajrul Amin, Ul A. Nissar, Parduman R. Sharma |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Keratinocytes
Ultraviolet Rays Eukaryotic Initiation Factor-2 Apoptosis Dermatology Biology medicine.disease_cause Endoplasmic Reticulum Biochemistry Calcium in biology Antioxidants Cell Line eIF-2 Kinase medicine Humans Calcium Signaling Phosphorylation Molecular Biology Membrane Potential Mitochondrial Endoplasmic reticulum Environmental stressor Cell Cycle Checkpoints Fibroblasts Endoplasmic Reticulum Stress Cell biology HaCaT Oxidative Stress medicine.anatomical_structure Unfolded protein response Unfolded Protein Response Keratinocyte Reactive Oxygen Species Oxidative stress Transcription Factor CHOP |
| Zdroj: | Journal of dermatological science. 75(1) |
| ISSN: | 1873-569X |
| Popis: | Background Exposure of skin to ultraviolet (UV) radiation, an environmental stressor induces number of adverse biological effects (photodamage), including cancer. The damage induced by UV-irradiation in skin cells is initiated by the photochemical generation of reactive oxygen species (ROS) and induction of endoplasmic reticulum (ER) stress and consequent activation of unfolded protein response (UPR). Objective To decipher cellular and molecular events responsible for UV-B mediated ER stress and UPR activation in skin cells. Methods The study was performed on human skin fibroblast (Hs68) and keratinocyte (HaCaT) cells exposed to UV-B radiations in lab conditions. Different parameters of UVB induced cellular and molecular changes were analyzed using Western-blotting, microscopic studies and flow cytometry. Results Our results depicted that UV-B induces an immediate ROS generation that resulted in emptying of ER Ca 2+ stores inducing ER stress and activation of PERK-peIF2α-CHOP pathway. Quenching ROS generation by anti-oxidants prevented Ca 2+ release and subsequent induction of ER stress and UPR activation. UV-B irradiation induced PERK dependent G2/M phase cell cycle arrest in Hs68 and G1/S phase cell cycle arrest in HaCaT. Also our study reflects that UV-B exposure leads to loss of mitochondrial membrane potential, activation of apoptotic cascade as evident by AnnexinV/PI staining, decreased expression of Bcl-2 and increased cleavage of PARP-1 protein. Conclusion UV-B induced Ca 2+ deficit within ER lumen was mediated by immediate ROS generation. Insufficient Ca 2+ concentration within ER lumen developed ER stress leading to UPR activation. These changes were reversed by use of anti-oxidants which quench ROS. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect