Activation of Nrf2 by Ginsenoside Rh3 protects retinal pigment epithelium cells and retinal ganglion cells from UV

Excessive Ultra-violet (UV) radiation shall induce damages to resident retinal pigment epithelium (RPE) cells (RPEs) and retinal ganglion cells (RGCs). Here we tested the potential activity of Ginsenoside Rh3 (“Rh3”) against the process. In cultured human RPEs and RGCs, pretreatment with Rh3 inhibit...

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Veröffentlicht in:Free radical biology & medicine 2018-03, Vol.117, p.238-246
Hauptverfasser: Tang, Chun-zhou, Li, Ke-Ran, Yu, Qing, Jiang, Qin, Yao, Jin, Cao, Cong
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creator Tang, Chun-zhou
Li, Ke-Ran
Yu, Qing
Jiang, Qin
Yao, Jin
Cao, Cong
description Excessive Ultra-violet (UV) radiation shall induce damages to resident retinal pigment epithelium (RPE) cells (RPEs) and retinal ganglion cells (RGCs). Here we tested the potential activity of Ginsenoside Rh3 (“Rh3”) against the process. In cultured human RPEs and RGCs, pretreatment with Rh3 inhibited UV-induced reactive oxygen species (ROS) production and following apoptotic/non-apoptotic cell death. Rh3 treatment in retinal cells induced nuclear-factor-E2-related factor 2 (Nrf2) activation, which was evidenced by Nrf2 protein stabilization and its nuclear translocation, along with transcription of antioxidant responsive element (ARE)-dependent genes (HO1, NOQ1 and GCLC). Nrf2 knockdown by targeted-shRNA almost abolished Rh3-induced retinal cell protection against UV. Further studies found that Rh3 induced microRNA-141 (“miR-141”) expression, causing downregulation of its targeted gene Keap1 in RPEs and RGCs. On the other hand, Rh3-induced Nrf2 activation and retinal cell protection were largely attenuated by the miR-141's inhibitor, antagomiR-141. In vivo, intravitreal injection of Rh3 inhibited retinal dysfunction by light damage in mice. Rh3 intravitreal injection also induced miR-141 expression, Keap1 downregulation and Nrf2 activation in mouse retinas. We conclude that Rh3 protects retinal cells from UV via activating Nrf2 signaling. [Display omitted] •Ginsenoside Rh3 protects human RPEs and RGCs from UV radiation.•Ginsenoside Rh3 activates Nrf2 signaling in retinal cells.•Nrf2 activation is required for Ginsenoside Rh3-mediated retinal cell protection.•Ginsenoside Rh3 up-regulates microRNA-141 to downregulate Keap1 in retinal cells.•Ginsenoside Rh3 protects mouse retina from light-induced damages in vivo.
doi_str_mv 10.1016/j.freeradbiomed.2018.02.001
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Here we tested the potential activity of Ginsenoside Rh3 (“Rh3”) against the process. In cultured human RPEs and RGCs, pretreatment with Rh3 inhibited UV-induced reactive oxygen species (ROS) production and following apoptotic/non-apoptotic cell death. Rh3 treatment in retinal cells induced nuclear-factor-E2-related factor 2 (Nrf2) activation, which was evidenced by Nrf2 protein stabilization and its nuclear translocation, along with transcription of antioxidant responsive element (ARE)-dependent genes (HO1, NOQ1 and GCLC). Nrf2 knockdown by targeted-shRNA almost abolished Rh3-induced retinal cell protection against UV. Further studies found that Rh3 induced microRNA-141 (“miR-141”) expression, causing downregulation of its targeted gene Keap1 in RPEs and RGCs. On the other hand, Rh3-induced Nrf2 activation and retinal cell protection were largely attenuated by the miR-141's inhibitor, antagomiR-141. 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[Display omitted] •Ginsenoside Rh3 protects human RPEs and RGCs from UV radiation.•Ginsenoside Rh3 activates Nrf2 signaling in retinal cells.•Nrf2 activation is required for Ginsenoside Rh3-mediated retinal cell protection.•Ginsenoside Rh3 up-regulates microRNA-141 to downregulate Keap1 in retinal cells.•Ginsenoside Rh3 protects mouse retina from light-induced damages in vivo.</description><identifier>ISSN: 0891-5849</identifier><identifier>EISSN: 1873-4596</identifier><identifier>DOI: 10.1016/j.freeradbiomed.2018.02.001</identifier><identifier>PMID: 29427790</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Enzyme Activation - drug effects ; Ginsenoside Rh3 ; Ginsenosides - pharmacology ; Humans ; Mice ; MicroRNA-141 ; NF-E2-Related Factor 2 - drug effects ; NF-E2-Related Factor 2 - metabolism ; Nrf2, UV radiation ; Oxidative stress ; Radiation Injuries, Experimental - drug therapy ; Retinal cells ; Retinal Ganglion Cells - drug effects ; Retinal Pigment Epithelium - drug effects ; Ultraviolet Rays - adverse effects</subject><ispartof>Free radical biology &amp; medicine, 2018-03, Vol.117, p.238-246</ispartof><rights>2018 Elsevier Inc.</rights><rights>Copyright © 2018 Elsevier Inc. 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subjects Animals
Enzyme Activation - drug effects
Ginsenoside Rh3
Ginsenosides - pharmacology
Humans
Mice
MicroRNA-141
NF-E2-Related Factor 2 - drug effects
NF-E2-Related Factor 2 - metabolism
Nrf2, UV radiation
Oxidative stress
Radiation Injuries, Experimental - drug therapy
Retinal cells
Retinal Ganglion Cells - drug effects
Retinal Pigment Epithelium - drug effects
Ultraviolet Rays - adverse effects
title Activation of Nrf2 by Ginsenoside Rh3 protects retinal pigment epithelium cells and retinal ganglion cells from UV
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