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

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

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 a...

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Main Authors: Yao, Jin, Bi, Hui-E, Sheng, Yi, Cheng, Li-Bo, Wendu, Ri-Le, Wang, Cheng-Hu, Cao, Guo-Fan, Jiang, Qin
Format: Online
Language:English
Published: Molecular Diversity Preservation International (MDPI) 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676843/
id pubmed-3676843
recordtype oai_dc
spelling pubmed-36768432013-07-02 Ultraviolet (UV) and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE) Cell Apoptosis Yao, Jin Bi, Hui-E Sheng, Yi Cheng, Li-Bo Wendu, Ri-Le Wang, Cheng-Hu Cao, Guo-Fan Jiang, Qin Article 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. Molecular Diversity Preservation International (MDPI) 2013-05-17 /pmc/articles/PMC3676843/ /pubmed/23685869 http://dx.doi.org/10.3390/ijms140510355 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Yao, Jin
Bi, Hui-E
Sheng, Yi
Cheng, Li-Bo
Wendu, Ri-Le
Wang, Cheng-Hu
Cao, Guo-Fan
Jiang, Qin
spellingShingle Yao, Jin
Bi, Hui-E
Sheng, Yi
Cheng, Li-Bo
Wendu, Ri-Le
Wang, Cheng-Hu
Cao, Guo-Fan
Jiang, Qin
Ultraviolet (UV) and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE) Cell Apoptosis
author_facet Yao, Jin
Bi, Hui-E
Sheng, Yi
Cheng, Li-Bo
Wendu, Ri-Le
Wang, Cheng-Hu
Cao, Guo-Fan
Jiang, Qin
author_sort Yao, Jin
title Ultraviolet (UV) and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE) Cell Apoptosis
title_short Ultraviolet (UV) and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE) Cell Apoptosis
title_full Ultraviolet (UV) and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE) Cell Apoptosis
title_fullStr Ultraviolet (UV) and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE) Cell Apoptosis
title_full_unstemmed Ultraviolet (UV) and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE) Cell Apoptosis
title_sort ultraviolet (uv) and hydrogen peroxide activate ceramide-er stress-ampk signaling axis to promote retinal pigment epithelium (rpe) cell apoptosis
description 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.
publisher Molecular Diversity Preservation International (MDPI)
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676843/
_version_ 1611984830884478976

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