SIRT1720 promotes survival of corneal epithelial cells via the P53 pathway SIRT1720 promotes survival of corneal epithelial cells
Main Article Content
Keywords
2.040 pRSV-T cell line, Acetyl-p53, SIRT1, SRT1720.
Abstract
Purpose: The protective role of SRT1720 (SIRT1 activator) against the oxidative stress caused by H2O2 in the corneal cell line was investigated in this study.
Methods: Human corneal (2.040 pRSV-T) cell lines were cultured and treated with SRT1720 (as SIRT1 activator) and nicotinamide (NAM, a SIRT1 inhibitor) and incubated with H2O2. The expression level of SIRT1, p53, and acetyl-p53 were measured by western blot. Propidium iodine/annexin V-FITC staining, and flow cytometry was used to evaluate apoptosis. The trypan blue assay was used to assess the morphological modifications that occurred after treatment, Pifithrin-α (PFT-α) was used to inhibit the p53 pathway.
Results: Under oxidative stress, SRT1720 caused a reduction in acetyl-p53 expression and increased SIRT1 expression. Under oxidative stress, SRT1720 suppressed apoptosis. In comparison, NAM promoted cell apoptosis under oxidative stress. NAM's destructive effect was removed by PFT-α, a suppressor of the p53 pathway. PFT-α reduced the morphological changes in 2.040 pRSV-T cell lines compared to NAM treatment and inhibited apoptosis.
Conclusions: The protective effects of the SIRT1 activator (SRT1720) indicate that H2O2 induces oxidative stress-associated cell damage. The results also encouraged us to consider using SRT1720 to improve corneal safety and reduce the adverse effects of oxidative damage.
References
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35. Qiu Y, Zhou X, Liu Y, Tan S, Li Y. The Role of Sirtuin-1 in Immune Response and Systemic Lupus Erythematosus. Front Immunol. 2021 Apr 26;12:632383.
36. Zhu J, Singh M, Selivanova G, Peuget S. Pifithrin-α alters p53 post-translational modifications pattern and differentially inhibits p53 target genes. Scientific reports. 2020 Jan 23;10(1):1-9.
37. Beumer TL, Roepers-Gajadien HL, Gademan IS, Buul PP van, Gil-Gomez G, Rutgers DH, et al. The role of the tumor suppressor p53 in spermatogenesis. Cell Death Differ. 1998 Aug;5(8):669–77.
38. Imai S, Kiess W. Therapeutic potential of SIRT1 and NAMPT-mediated NAD biosynthesis in type 2 diabetes. Front Biosci. 2009 Jan 1;14:2983–95.
39. Doganay S, Borazan M, Iraz M, Cigremis Y. The effect of resveratrol in experimental cataract model formed by sodium selenite. Current eye research. 2006 Jan 1;31(2):147-53.
40. Bäckesjö CM, Li Y, Lindgren U, Haldosén LA. Activation of Sirt1 decreases adipocyte formation during osteoblast differentiation of mesenchymal stem cells. Cells Tissues Organs. 2009;189(1-4):93-7.
2. Mimura T, Kaji Y, Noma H, Funatsu H, Okamoto S. The role of SIRT1 in ocular aging. Experimental Eye Research. 2013 Nov;116:17–26.
3. Wenk J, Brenneisen P, Meewes C, Wlaschek M, Peters T, Blaudschun R, et al. UV-induced oxidative stress and photoaging. CURRENT PROBLEMS IN DERMATOLOGY-BASEL-. 2001;29:83–94.
4. Choi S-I, Dadakhujaev S, Ryu H, im Kim T, Kim EK. Melatonin protects against oxidative stress in granular corneal dystrophy type 2 corneal fibroblasts by mechanisms that involve membrane melatonin receptors. Journal of Pineal Research. 2011;51(1):94–103.
5. Vallabh NA, Romano V, Willoughby CE. Mitochondrial dysfunction and oxidative stress in corneal disease. Mitochondrion. 2017 Sep;36:103–13.
6. Güllülü Ö, Hehlgans S, Rödel C, Fokas E, Rödel F. Tumor Suppressor Protein p53 and Inhibitor of Apoptosis Proteins in Colorectal Cancer—A Promising Signaling Network for Therapeutic Interventions. Cancers. 2021 Jan;13(4):624.
7. Zheng T, Lu Y. SIRT1 Protects Human Lens Epithelial Cells Against Oxidative Stress by Inhibiting p53-Dependent Apoptosis. Current Eye Research. 2016 Aug 2;41(8):1068–75.
8. Dittenhafer-Reed KE, Feldman JL, Denu JM. Catalysis and mechanistic insights on Sirtuin activation. Chembiochem. 2011 Jan 24;12(2):281–9.
9. Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, Bemis JE. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007 Nov;450(7170):712-6.
10. Tsai T-Y, Chen T-C, Wang I-J, Yeh C-Y, Su M-J, Chen R-H, et al. The Effect of Resveratrol on Protecting Corneal Epithelial Cells from Cytotoxicity Caused by Moxifloxacin and Benzalkonium Chloride. Investigative Ophthalmology & Visual Science. 2015 Mar 5;56(3):1575–84.
11. Zeng L, Chen R, Liang F, Tsuchiya H, Murai H, Nakahashi T, Iwai K, Takahashi T, Kanda T, Morimoto S. Silent information regulator, Sirtuin 1, and age‐related diseases. Geriatrics & gerontology international. 2009 Mar;9(1):7-15.
13. Brooks CL, Gu W. Ubiquitination, phosphorylation and acetylation: the molecular basis for p53 regulation. Current opinion in cell biology. 2003 Apr 1;15(2):164-71.
14. Luo J, Nikolaev AY, Imai SI, Chen D, Su F, Shiloh A, Guarente L, Gu W. Negative control of p53 by Sir2α promotes cell survival under stress. Cell. 2001 Oct 19;107(2):137-48.
15. Yamamoto H, Schoonjans K, Auwerx J. Sirtuin functions in health and disease. Molecular endocrinology. 2007 Aug 1;21(8):1745-55.
16. Al-Sudani B, H. Ragazzon-Smith A, Aziz A, Alansari R, Ferry N, Krstic-Demonacos M, et al. Circular and linear: a tale of aptamer selection for the activation of SIRT1 to induce death in cancer cells. RSC Advances. 2020;10(73):45008–18.
17. Tariq R, Arif I, Basma T, Al-Sudani, Al-Sudani B. SIRTUIN 1, a novel approach in the treatment of type 2 diabetes mellitus. Systematic Reviews in Pharmacy. 2020 Nov 1;11:117–28.
18. Mahmood T, Yang P-C. Western Blot: Technique, Theory, and Trouble Shooting. N Am J Med Sci. 2012 Sep;4(9):429–34.
19. Telford W, Tamul K, Bradford J. Measurement and characterization of apoptosis by flow cytometry. Current Protocols in Cytometry. 2016 Jul;77(1):9-49.
20. Strober W. Trypan Blue Exclusion Test of Cell Viability. Current Protocols in Immunology. 2015;111(1):A3.B.1-A3.B.3.
21. Zhou M, Luo J, Zhang H. Role of Sirtuin 1 in the pathogenesis of ocular disease (Review). International Journal of Molecular Medicine. 2018 Aug 1;42(1):13–20.
22. Liu T, Ma X, Ouyang T, Chen H, Lin J, Liu J, et al. SIRT1 reverses senescence via enhancing autophagy and attenuates oxidative stress-induced apoptosis through promoting p53 degradation. International Journal of Biological Macromolecules. 2018 Oct;117:225–34.
23. Vazquez A, Bond EE, Levine AJ, Bond GL. The genetics of the p53 pathway, apoptosis and cancer therapy. Nat Rev Drug Discov. 2008 Dec;7(12):979–87.
24. Riley T, Sontag E, Chen P, Levine A. Transcriptional control of human p53-regulated genes. Nature reviews Molecular cell biology. 2008 May;9(5):402-12.
25. Niwa-Kawakita M, Ferhi O, Soilihi H, Le Bras M, Lallemand-Breitenbach V, de Thé H. PML is a ROS sensor activating p53 upon oxidative stress. Journal of Experimental Medicine. 2017 Nov 6;214(11):3197-206.
26. Brooks CL, Gu W. p53 Ubiquitination: Mdm2 and Beyond. Molecular Cell. 2006 Feb 3;21(3):307–15.
27. Lin Z, Yang H, Kong Q, Li J, Lee SM, Gao B, Dong H, Wei J, Song J, Zhang DD, Fang D. USP22 antagonizes p53 transcriptional activation by deubiquitinating Sirt1 to suppress cell apoptosis and is required for mouse embryonic development. Molecular cell. 2012 May 25;46(4):484-94.
28. Niederer F, Ospelt C, Brentano F, Hottiger MO, Gay RE, Gay S, Detmar M, Kyburz D. SIRT1 overexpression in the rheumatoid arthritis synovium contributes to proinflammatory cytokine production and apoptosis resistance. Annals of the rheumatic diseases. 2011 Oct 1;70(10):1866-73.
29. Bitterman KJ, Anderson RM, Cohen HY, Latorre-Esteves M, Sinclair DA. Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. Journal of Biological Chemistry. 2002 Nov 22;277(47):45099-107.
30. Liang J, Cao R, Wang X, Zhang Y, Wang P, Gao H, et al. Mitochondrial PKM2 regulates oxidative stress-induced apoptosis by stabilizing Bcl2. Cell Res. 2017 Mar;27(3):329–51.
31. Komarov PG, Komarova EA, Kondratov RV, Christov-Tselkov K, Coon JS, Chernov MV, Gudkov AV. A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science. 1999 Sep 10;285(5434):1733-7.
32. Villalba JM, Alcaín FJ. Sirtuin activators and inhibitors. BioFactors. 2012;38(5):349–59.
33. Liu C, Vojnovic D, Kochevar IE, Jurkunas UV. UV-A Irradiation Activates Nrf2-Regulated Antioxidant Defense and Induces p53/Caspase3-Dependent Apoptosis in Corneal Endothelial Cells. Investigative Ophthalmology & Visual Science. 2016 Apr 29;57(4):2319–27.
34. Wu J, Liang W, Tian Y, Ma F, Huang W, Jia Y, et al. Inhibition of P53/miR-34a improves diabetic endothelial dysfunction via activation of SIRT1. Journal of Cellular and Molecular Medicine. 2019;23(5):3538–48.
35. Qiu Y, Zhou X, Liu Y, Tan S, Li Y. The Role of Sirtuin-1 in Immune Response and Systemic Lupus Erythematosus. Front Immunol. 2021 Apr 26;12:632383.
36. Zhu J, Singh M, Selivanova G, Peuget S. Pifithrin-α alters p53 post-translational modifications pattern and differentially inhibits p53 target genes. Scientific reports. 2020 Jan 23;10(1):1-9.
37. Beumer TL, Roepers-Gajadien HL, Gademan IS, Buul PP van, Gil-Gomez G, Rutgers DH, et al. The role of the tumor suppressor p53 in spermatogenesis. Cell Death Differ. 1998 Aug;5(8):669–77.
38. Imai S, Kiess W. Therapeutic potential of SIRT1 and NAMPT-mediated NAD biosynthesis in type 2 diabetes. Front Biosci. 2009 Jan 1;14:2983–95.
39. Doganay S, Borazan M, Iraz M, Cigremis Y. The effect of resveratrol in experimental cataract model formed by sodium selenite. Current eye research. 2006 Jan 1;31(2):147-53.
40. Bäckesjö CM, Li Y, Lindgren U, Haldosén LA. Activation of Sirt1 decreases adipocyte formation during osteoblast differentiation of mesenchymal stem cells. Cells Tissues Organs. 2009;189(1-4):93-7.
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Aug 24, 2022
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Al-Sudani, B. . (2022). SIRT1720 promotes survival of corneal epithelial cells via the P53 pathway: SIRT1720 promotes survival of corneal epithelial cells. Journal of Population Therapeutics and Clinical Pharmacology, 29(03). https://doi.org/10.47750/jptcp.2022.906
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All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.