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Escin activates AKT-Nrf2 signaling to protect retinal pigment epithelium cells from oxidative stress.
Biochem Biophys Res Commun. 2015 Dec 25; 468(4):541-7.BB

Abstract

Here we explored the anti-oxidative and cytoprotective potentials of escin, a natural triterpene-saponin, against hydrogen peroxide (H2O2) in retinal pigment epithelium (RPE) cells. We showed that escin remarkably attenuated H2O2-induced death and apoptosis of established (ARPE-19) and primary murine RPE cells. Meanwhile, ROS production and lipid peroxidation by H2O2 were remarkably inhibited by escin. Escin treatment in RPE cells resulted in NF-E2-related factor 2 (Nrf2) signaling activation, evidenced by transcription of anti-oxidant-responsive element (ARE)-regulated genes, including HO-1, NQO-1 and SRXN-1. Knockdown of Nrf2 through targeted shRNAs/siRNAs alleviated escin-mediated ARE gene transcription, and almost abolished escin-mediated anti-oxidant activity and RPE cytoprotection against H2O2. Reversely, escin was more potent against H2O2 damages in Nrf2-over-expressed ARPE-19 cells. Further studies showed that escin-induced Nrf2 activation in RPE cells required AKT signaling. AKT inhibitors (LY294002 and perifosine) blocked escin-induced AKT activation, and dramatically inhibited Nrf2 phosphorylation, its cytosol accumulation and nuclear translocation in RPE cells. Escin-induced RPE cytoprotection against H2O2 was also alleviated by the AKT inhibitors. Together, these results demonstrate that escin protects RPE cells from oxidative stress possibly through activating AKT-Nrf2 signaling.

Authors+Show Affiliations

Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, China; Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, China.The First People Hospital of Xiaoshan, Hangzhou, China.Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, China; Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, China.Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, China; Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, China.Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, China; Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, China. Electronic address: eyedrchenminzj@163.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26505797

Citation

Wang, Kaijun, et al. "Escin Activates AKT-Nrf2 Signaling to Protect Retinal Pigment Epithelium Cells From Oxidative Stress." Biochemical and Biophysical Research Communications, vol. 468, no. 4, 2015, pp. 541-7.
Wang K, Jiang Y, Wang W, et al. Escin activates AKT-Nrf2 signaling to protect retinal pigment epithelium cells from oxidative stress. Biochem Biophys Res Commun. 2015;468(4):541-7.
Wang, K., Jiang, Y., Wang, W., Ma, J., & Chen, M. (2015). Escin activates AKT-Nrf2 signaling to protect retinal pigment epithelium cells from oxidative stress. Biochemical and Biophysical Research Communications, 468(4), 541-7. https://doi.org/10.1016/j.bbrc.2015.10.117
Wang K, et al. Escin Activates AKT-Nrf2 Signaling to Protect Retinal Pigment Epithelium Cells From Oxidative Stress. Biochem Biophys Res Commun. 2015 Dec 25;468(4):541-7. PubMed PMID: 26505797.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Escin activates AKT-Nrf2 signaling to protect retinal pigment epithelium cells from oxidative stress. AU - Wang,Kaijun, AU - Jiang,Yiqian, AU - Wang,Wei, AU - Ma,Jian, AU - Chen,Min, Y1 - 2015/10/24/ PY - 2015/10/03/received PY - 2015/10/21/accepted PY - 2015/10/28/entrez PY - 2015/10/28/pubmed PY - 2016/4/22/medline KW - AKT and Nrf2 signaling KW - Escin KW - Oxidative stress KW - Retinal pigment epithelium cells SP - 541 EP - 7 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 468 IS - 4 N2 - Here we explored the anti-oxidative and cytoprotective potentials of escin, a natural triterpene-saponin, against hydrogen peroxide (H2O2) in retinal pigment epithelium (RPE) cells. We showed that escin remarkably attenuated H2O2-induced death and apoptosis of established (ARPE-19) and primary murine RPE cells. Meanwhile, ROS production and lipid peroxidation by H2O2 were remarkably inhibited by escin. Escin treatment in RPE cells resulted in NF-E2-related factor 2 (Nrf2) signaling activation, evidenced by transcription of anti-oxidant-responsive element (ARE)-regulated genes, including HO-1, NQO-1 and SRXN-1. Knockdown of Nrf2 through targeted shRNAs/siRNAs alleviated escin-mediated ARE gene transcription, and almost abolished escin-mediated anti-oxidant activity and RPE cytoprotection against H2O2. Reversely, escin was more potent against H2O2 damages in Nrf2-over-expressed ARPE-19 cells. Further studies showed that escin-induced Nrf2 activation in RPE cells required AKT signaling. AKT inhibitors (LY294002 and perifosine) blocked escin-induced AKT activation, and dramatically inhibited Nrf2 phosphorylation, its cytosol accumulation and nuclear translocation in RPE cells. Escin-induced RPE cytoprotection against H2O2 was also alleviated by the AKT inhibitors. Together, these results demonstrate that escin protects RPE cells from oxidative stress possibly through activating AKT-Nrf2 signaling. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/26505797/Escin_activates_AKT_Nrf2_signaling_to_protect_retinal_pigment_epithelium_cells_from_oxidative_stress_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(15)30816-0 DB - PRIME DP - Unbound Medicine ER -