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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2013 May 21

PMID 23685869

Citations 33

Authors

Jin Yao

Hui-E Bi

Yi Sheng

Li-Bo Cheng

Ri-Le Wendu

Cheng-Hu Wang

Guo-Fan Cao

Qin Jiang

Affiliations

Soon will be listed here.

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.

Citing Articles

Signaling Pathways in Retinal Pigment Epithelium (RPE) Cells in Response to Stress Conditions of Age-Related Macular Degeneration (AMD).

Armento A, Almansa-Garcia A, Sen M, Merle D, Arango-Gonzalez B, Ueffing M Adv Exp Med Biol. 2025; 1468:345-349.

PMID: 39930220 DOI: 10.1007/978-3-031-76550-6_57.

m6A-Mediated Upregulation of Imprinted in Prader-Willi Syndrome Induces Aberrant Apical-Basal Polarization and Oxidative Damage in RPE Cells.

Wang Y, Zhang Y, Ding Z, Zhang Y, Sun R, Zhu H Invest Ophthalmol Vis Sci. 2024; 65(2):10.

PMID: 38315495 PMC: 10851782. DOI: 10.1167/iovs.65.2.10.

Spatiotemporal roles of AMPK in PARP-1- and autophagy-dependent retinal pigment epithelial cell death caused by UVA.

Wu A, Sekar P, Huang D, Hsu S, Chan C, Lin W J Biomed Sci. 2023; 30(1):91.

PMID: 37936170 PMC: 10629085. DOI: 10.1186/s12929-023-00978-4.

Chitooligosaccharides Derivatives Protect ARPE-19 Cells against Acrolein-Induced Oxidative Injury.

Yang C, Yang R, Gu M, Hao J, Wang S, Li C Mar Drugs. 2023; 21(3).

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Role of Mitochondria in Retinal Pigment Epithelial Aging and Degeneration.

Tong Y, Zhang Z, Wang S Front Aging. 2022; 3:926627.

PMID: 35912040 PMC: 9337215. DOI: 10.3389/fragi.2022.926627.

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