Ultraviolet (UV) and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE) Cell Apoptosis |
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| Authors: | Jin Yao Hui-E Bi Yi Sheng Li-Bo Cheng Ri-Le Wendu Cheng-Hu Wang Guo-Fan Cao Qin Jiang |
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| Affiliation: | 1.The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029, China; E-Mails: (H.-E.B.); (Y.S.); (L.-B.C.); (R.-L.W.); (C.-H.W.); (G.-F.C.);2.Eye Department, Li-Yang City Hospital of Traditional Chinese Medicine, Li-Yang City 213300, China |
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| Abstract: | Ultraviolet (UV) radiation and reactive oxygen species (ROS) impair the physiological functions of retinal pigment epithelium (RPE) cells by inducing cell apoptosis, which is the main cause of age-related macular degeneration (AMD). The mechanism by which UV/ROS induces RPE cell death is not fully addressed. Here, we observed the activation of a ceramide-endoplasmic reticulum (ER) stress-AMP activated protein kinase (AMPK) signaling axis in UV and hydrogen peroxide (H2O2)-treated RPE cells. UV and H2O2 induced an early ceramide production, profound ER stress and AMPK activation. Pharmacological inhibitors against ER stress (salubrinal), ceramide production (fumonisin B1) and AMPK activation (compound C) suppressed UV- and H2O2-induced RPE cell apoptosis. Conversely, cell permeable short-chain C6 ceramide and AMPK activator AICAR (5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide) mimicked UV and H2O2’s effects and promoted RPE cell apoptosis. Together, these results suggest that UV/H2O2 activates the ceramide-ER stress-AMPK signaling axis to promote RPE cell apoptosis. |
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| Keywords: | age-related macular degeneration (AMD) UV ROS RPE cell apoptosis ceramide ER stress and AMPK |
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