期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 14, 期 5, 页码 10355-10368出版社
MDPI AG
DOI: 10.3390/ijms140510355
关键词
age-related macular degeneration (AMD); UV; ROS; RPE cell apoptosis; ceramide; ER stress and AMPK
资金
- National Natural Science Foundation of China [81070744, 81271028]
- post-doc fund of Jiangsu Province [1002009B]
- Medical Science and Technology Development Project Fund of Nanjing [ZKX12047, YKK12208, YKK12207]
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-beta-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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