title: Ultraviolet (UV) and hydrogen peroxide activate ceramide-ER stress-AMPK signaling axis to promote retinal pigment epithelium (RPE) cell apoptosis.
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.
authors.affiliation: The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029, China. dryaojin@yahoo.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Yao
authors.forename: Hui-E
authors.initials: HE
authors.lastname: Bi
authors.forename: Yi
authors.initials: Y
authors.lastname: Sheng
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Cheng
authors.forename: Ri-Le
authors.initials: RL
authors.lastname: Wendu
authors.forename: Cheng-Hu
authors.initials: CH
authors.lastname: Wang
authors.forename: Guo-Fan
authors.initials: GF
authors.lastname: Cao
authors.forename: Qin
authors.initials: Q
authors.lastname: Jiang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D002518:Ceramides / Q000378:metabolism* / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D037341:Fumonisins / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D055213:Retinal Pigment Epithelium / Q000166:cytology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014466:Ultraviolet Rays
chemical_list: D002518:Ceramides; D002934:Cinnamates; D037341:Fumonisins; D016877:Oxidants; C496827:salubrinal; C101954:N-caproylsphingosine; C056933:fumonisin B1; D006861:Hydrogen Peroxide; D055372:AMP-Activated Protein Kinases; D013890:Thiourea