Int. J. Mol. Sci. 2013, 14(5), 10355-10368; doi:10.3390/ijms140510355
Article

Ultraviolet (UV) and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE) Cell Apoptosis

1,†,* email, 1,†email, 1,†email, 1,2email, 1email, 1email, 1email and 1,* email
1 The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029, China 2 Eye Department, Li-Yang City Hospital of Traditional Chinese Medicine, Li-Yang City 213300, China These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 24 November 2012; in revised form: 15 April 2013 / Accepted: 2 May 2013 / Published: 17 May 2013
(This article belongs to the Special Issue UV-Induced Cell Death 2012)
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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.
Keywords: age-related macular degeneration (AMD); UV; ROS; RPE cell apoptosis; ceramide; ER stress and AMPK

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MDPI and ACS Style

Yao, J.; Bi, H.-E.; Sheng, Y.; Cheng, L.-B.; Wendu, R.-L.; Wang, C.-H.; Cao, G.-F.; Jiang, Q. Ultraviolet (UV) and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE) Cell Apoptosis. Int. J. Mol. Sci. 2013, 14, 10355-10368.

AMA Style

Yao J, Bi H-E, Sheng Y, Cheng L-B, Wendu R-L, Wang C-H, Cao G-F, Jiang Q. Ultraviolet (UV) and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE) Cell Apoptosis. International Journal of Molecular Sciences. 2013; 14(5):10355-10368.

Chicago/Turabian Style

Yao, Jin; Bi, Hui-E; Sheng, Yi; Cheng, Li-Bo; Wendu, Ri-Le; Wang, Cheng-Hu; Cao, Guo-Fan; Jiang, Qin. 2013. "Ultraviolet (UV) and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE) Cell Apoptosis." Int. J. Mol. Sci. 14, no. 5: 10355-10368.

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