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Salvianolic Acid B (Sal B) Protects Retinal Pigment Epithelial Cells from Oxidative Stress-Induced Cell Death by Activating Glutaredoxin 1 (Grx1).
Int J Mol Sci. 2016 Nov 03; 17(11)IJ

Abstract

Protein glutathionylation, defined as the formation of protein mixed disulfides (PSSG) between cysteine residues and glutathione (GSH), can lead to cell death. Glutaredoxin 1 (Grx1) is a thiol repair enzyme which catalyzes the reduction of PSSG. Therefore, Grx1 exerts strong anti-apoptotic effects by improving the redox state, especially in times of oxidative stress. However, there is currently no compound that is identified as a Grx1 activator. In this study, we identified and characterized Salvianolic acid B (Sal B), a natural compound, as a Grx1 inducer, which potently protected retinal pigment epithelial (RPE) cells from oxidative injury. Our results showed that treatment with Sal B protected primary human RPE cells from H₂O₂-induced cell damage. Interestingly, we found Sal B pretreatment upregulated Grx1 expression in RPE cells in a time- and dose-dependent manner. Furthermore, NF-E2-related factor 2 (Nrf2), the key transcription factor that regulates the expression of Grx1, was activated in Sal B treated RPE cells. Further investigation showed that knockdown of Grx1 by small interfering RNA (siRNA) significantly reduced the protective effects of Sal B. We conclude that Sal B protects RPE cells against H₂O₂-induced cell injury through Grx1 induction by activating Nrf2 pathway, thus preventing lethal accumulation of PSSG and reversing oxidative damage.

Authors+Show Affiliations

Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA. xiaobin.liu@unthsc.edu.Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA. Christy.Xavier@unthsc.edu.Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA. jjann@uga.edu.Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA. hongli.wu@unthsc.edu. North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA. hongli.wu@unthsc.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27827892

Citation

Liu, Xiaobin, et al. "Salvianolic Acid B (Sal B) Protects Retinal Pigment Epithelial Cells From Oxidative Stress-Induced Cell Death By Activating Glutaredoxin 1 (Grx1)." International Journal of Molecular Sciences, vol. 17, no. 11, 2016.
Liu X, Xavier C, Jann J, et al. Salvianolic Acid B (Sal B) Protects Retinal Pigment Epithelial Cells from Oxidative Stress-Induced Cell Death by Activating Glutaredoxin 1 (Grx1). Int J Mol Sci. 2016;17(11).
Liu, X., Xavier, C., Jann, J., & Wu, H. (2016). Salvianolic Acid B (Sal B) Protects Retinal Pigment Epithelial Cells from Oxidative Stress-Induced Cell Death by Activating Glutaredoxin 1 (Grx1). International Journal of Molecular Sciences, 17(11).
Liu X, et al. Salvianolic Acid B (Sal B) Protects Retinal Pigment Epithelial Cells From Oxidative Stress-Induced Cell Death By Activating Glutaredoxin 1 (Grx1). Int J Mol Sci. 2016 Nov 3;17(11) PubMed PMID: 27827892.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Salvianolic Acid B (Sal B) Protects Retinal Pigment Epithelial Cells from Oxidative Stress-Induced Cell Death by Activating Glutaredoxin 1 (Grx1). AU - Liu,Xiaobin, AU - Xavier,Christy, AU - Jann,Jamieson, AU - Wu,Hongli, Y1 - 2016/11/03/ PY - 2016/07/14/received PY - 2016/10/08/revised PY - 2016/10/31/accepted PY - 2016/11/10/entrez PY - 2016/11/10/pubmed PY - 2017/4/13/medline KW - glutaredoxin 1 KW - oxidative stress KW - protein glutathionylation KW - retinal pigment epithelial cells KW - salvianolic acid B JF - International journal of molecular sciences JO - Int J Mol Sci VL - 17 IS - 11 N2 - Protein glutathionylation, defined as the formation of protein mixed disulfides (PSSG) between cysteine residues and glutathione (GSH), can lead to cell death. Glutaredoxin 1 (Grx1) is a thiol repair enzyme which catalyzes the reduction of PSSG. Therefore, Grx1 exerts strong anti-apoptotic effects by improving the redox state, especially in times of oxidative stress. However, there is currently no compound that is identified as a Grx1 activator. In this study, we identified and characterized Salvianolic acid B (Sal B), a natural compound, as a Grx1 inducer, which potently protected retinal pigment epithelial (RPE) cells from oxidative injury. Our results showed that treatment with Sal B protected primary human RPE cells from H₂O₂-induced cell damage. Interestingly, we found Sal B pretreatment upregulated Grx1 expression in RPE cells in a time- and dose-dependent manner. Furthermore, NF-E2-related factor 2 (Nrf2), the key transcription factor that regulates the expression of Grx1, was activated in Sal B treated RPE cells. Further investigation showed that knockdown of Grx1 by small interfering RNA (siRNA) significantly reduced the protective effects of Sal B. We conclude that Sal B protects RPE cells against H₂O₂-induced cell injury through Grx1 induction by activating Nrf2 pathway, thus preventing lethal accumulation of PSSG and reversing oxidative damage. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/27827892/Salvianolic_Acid_B__Sal_B__Protects_Retinal_Pigment_Epithelial_Cells_from_Oxidative_Stress_Induced_Cell_Death_by_Activating_Glutaredoxin_1__Grx1__ L2 - http://www.mdpi.com/resolver?pii=ijms17111835 DB - PRIME DP - Unbound Medicine ER -