Salvianolic Acid B (Sal B) Protects Retinal Pigment Epithelial Cells from Oxidative Stress-Induced Cell Death by Activating Glutaredoxin 1 (Grx1).
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 ofGrx1by 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.
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.
Xiaobin
X
Liu
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.
Christy
C
Xavier
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.
Jamieson
J
Jann
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.
Hongli
H
Wu
D000975:Antioxidants / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D004220:Disulfides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005333:Fetus; D005786:Gene Expression Regulation; D054477:Glutaredoxins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051267:NF-E2-Related Factor 2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D053630:Depsides
D000975:Antioxidants; D001572:Benzofurans; D004220:Disulfides; D004365:Drugs, Chinese Herbal; D054477:Glutaredoxins; D005978:Glutathione; D006861:Hydrogen Peroxide; D051267:NF-E2-Related Factor 2; D034741:RNA, Small Interfering; C516005:GLRX protein, human; C495635:NFE2L2 protein, human; C076944:salvianolic acid B; D053630:Depsides
glutaredoxin 1; oxidative stress; protein glutathionylation; retinal pigment epithelial cells; salvianolic acid B