Curcumin Attenuates Oxidative Stress-Induced Effects on TGF-β Expression and NF-κB Signaling in Bovine Aortic Endothelial Cells
Abstract
Objectives: The endothelium constitutes a significant part of the vasculature. Oxidative stress, an imbalance between the generation of reactive oxygen species (ROS) and the antioxidant defense system, contributes to the impairment of endothelial function. ROS regulate several signaling pathways, such as transforming growth factor β (TGF-β) and nuclear factor kappa B (NF-κB). This study aimed to investigate the effects of curcumin, a polyphenol with antioxidant properties, on these two molecules in endothelial cells treated with hydrogen peroxide (H2O2).
Methods: Cultured Bovine aortic endothelial cells (BAECs) were treated with different concentrations of H2O2 (20 µM, 40 µM, and 200μM) for 1 and 24 hours in the absence and presence of curcumin. TGF-β expression was detected by quantitative real-time PCR analysis, and phosphorylation of NF-κB-p65 was examined by western blot.
Results: H2O2 up-regulates TGF-β mRNA expression and induces the phosphorylation of the p65 subunit of NF-kB in a dose-dependent manner in BAECs. Curcumin inhibited both H2O2-stimulated TGF-β expression and phosphorylation of NF-κB-p65 in these cells.
Conclusion: The findings demonstrate that curcumin reduces TGF-β mRNA expression and inhibits NFκB-p65 phosphorylation in endothelial cells.
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21. Yaser Mohassel , S.A., Shayan Mostafae , Mohammad Taghi Goodarzi Assessing the Possible Association between Polymorphism of C677T MTHFR with Preeclampsia Risk: A Systematic Review and Bayesian Hierarchical Meta-Analysis. Acta Biochimica Iranica, 2023. 1(1): p. 3-11.
22. Sattar Gorgani-Firuzjaee, R.M., Resveratrol reduces high glucose-induced de-novo lipogenesis through mTOR mediated induction of autophagy in HepG2 cells. Acta Biochimica Iranica, 2023. 1(1): p. 32-39.
23. Mishina, N.M., P.A. Tyurin-Kuzmin, K.N. Markvicheva, A.V. Vorotnikov, V.A. Tkachuk, V. Laketa, et al., Does cellular hydrogen peroxide diffuse or act locally? Antioxid Redox Signal, 2011. 14(1): p. 1-7.
24. Eyries, M., T. Collins, and L.M. Khachigian, Modulation of growth factor gene expression in vascular cells by oxidative stress. Endothelium, 2004. 11(2): p. 133-9.
25. Morikawa, M., R. Derynck, and K. Miyazono, TGF-β and the TGF-β Family: Context-Dependent Roles in Cell and Tissue Physiology. Cold Spring Harb Perspect Biol, 2016. 8(5).
26. Shin, H., H.G. Yoo, S. Inui, S. Itami, I.G. Kim, A.R. Cho, et al., Induction of transforming growth factor-beta 1 by androgen is mediated by reactive oxygen species in hair follicle dermal papilla cells. BMB Rep, 2013. 46(9): p. 460-4.
27. Sintara, K., D. Thong-Ngam, S. Patumraj, N. Klaikeaw, and T. Chatsuwan, Curcumin suppresses gastric NF-kappaB activation and macromolecular leakage in Helicobacter pylori-infected rats. World J Gastroenterol, 2010. 16(32): p. 4039-46.
28. Bhaskar, S., P.R. Sudhakaran, and A. Helen, Quercetin attenuates atherosclerotic inflammation and adhesion molecule expression by modulating TLR-NF-κB signaling pathway. Cell Immunol, 2016. 310: p. 131-140.
29. Lawrence, T., The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol, 2009. 1(6): p. a001651.
30. Yao, Q.Y., B.L. Xu, J.Y. Wang, H.C. Liu, S.C. Zhang, and C.T. Tu, Inhibition by curcumin of multiple sites of the transforming growth factor-beta1 signalling pathway ameliorates the progression of liver fibrosis induced by carbon tetrachloride in rats. BMC Complement Altern Med, 2012. 12: p. 156.
31. Gaedeke, J., N.A. Noble, and W.A. Border, Curcumin blocks multiple sites of the TGF-beta signaling cascade in renal cells. Kidney Int, 2004. 66(1): p. 112-20.
32. Dikshit, P., A. Goswami, A. Mishra, M. Chatterjee, and N.R. Jana, Curcumin induces stress response, neurite outgrowth and prevent NF-kappaB activation by inhibiting the proteasome function. Neurotox Res, 2006. 9(1): p. 29-37.
33. Samuhasaneeto, S., D. Thong-Ngam, O. Kulaputana, D. Suyasunanont, and N. Klaikeaw, Curcumin decreased oxidative stress, inhibited NF-kappaB activation, and improved liver pathology in ethanol-induced liver injury in rats. J Biomed Biotechnol, 2009. 2009: p. 981963.
2. Silva, B.R., L. Pernomian, and L.M. Bendhack, Contribution of oxidative stress to endothelial dysfunction in hypertension. Front Physiol, 2012. 3: p. 441.
3. Vaziri, N.D., Causal link between oxidative stress, inflammation, and hypertension. Iran J Kidney Dis, 2008. 2(1): p. 1-10.
4. Soetikno, V., F.R. Sari, A.P. Lakshmanan, S. Arumugam, M. Harima, K. Suzuki, et al., Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the Nrf2-keap1 pathway. Mol Nutr Food Res, 2013. 57(9): p. 1649-59.
5. Davignon, J. and P. Ganz, Role of endothelial dysfunction in atherosclerosis. Circulation, 2004. 109(23 Suppl 1): p. Iii27-32.
6. Sitia, S., L. Tomasoni, F. Atzeni, G. Ambrosio, C. Cordiano, A. Catapano, et al., From endothelial dysfunction to atherosclerosis. Autoimmun Rev, 2010. 9(12): p. 830-4.
7. Li, M.O., Y.Y. Wan, S. Sanjabi, A.K. Robertson, and R.A. Flavell, Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol, 2006. 24: p. 99-146.
8. ten Dijke, P. and C.S. Hill, New insights into TGF-beta-Smad signalling. Trends Biochem Sci, 2004. 29(5): p. 265-73.
9. Burch, M.L., S.N. Yang, M.L. Ballinger, R. Getachew, N. Osman, and P.J. Little, TGF-beta stimulates biglycan synthesis via p38 and ERK phosphorylation of the linker region of Smad2. Cell Mol Life Sci, 2010. 67(12): p. 2077-90.
10. Yang, S.N., M.L. Burch, L.R. Tannock, S. Evanko, N. Osman, and P.J. Little, Transforming growth factor-β regulation of proteoglycan synthesis in vascular smooth muscle: contribution to lipid binding and accelerated atherosclerosis in diabetes. J Diabetes, 2010. 2(4): p. 233-42.
11. Yang, S.N., M.L. Burch, R. Getachew, M.L. Ballinger, N. Osman, and P.J. Little, Growth factor-mediated hyper-elongation of glycosaminoglycan chains on biglycan requires transcription and translation. Arch Physiol Biochem, 2009. 115(3): p. 147-54.
12. Kassan, M., S.K. Choi, M. Galán, A. Bishop, K. Umezawa, M. Trebak, et al., Enhanced NF-κB activity impairs vascular function through PARP-1-, SP-1-, and COX-2-dependent mechanisms in type 2 diabetes. Diabetes, 2013. 62(6): p. 2078-87.
13. Kondylis, V., S. Kumari, K. Vlantis, and M. Pasparakis, The interplay of IKK, NF-κB and RIPK1 signaling in the regulation of cell death, tissue homeostasis and inflammation. Immunol Rev, 2017. 277(1): p. 113-127.
14. Christian, F., E.L. Smith, and R.J. Carmody, The Regulation of NF-κB Subunits by Phosphorylation. Cells, 2016. 5(1).
15. Liu, T., L. Zhang, D. Joo, and S.C. Sun, NF-κB signaling in inflammation. Signal Transduct Target Ther, 2017. 2: p. 17023-.
16. Pires, B.R.B., R. Silva, G.M. Ferreira, and E. Abdelhay, NF-kappaB: Two Sides of the Same Coin. Genes (Basel), 2018. 9(1).
17. Alekseevna, R.V., K.D. Alexandrovna, D.A. Pavlovich, B.Y. Evgenievich, and N.S. Viktorovich. NUCLEAR FACTOR KAPPA B AS A POTENTIAL TARGET FOR PHARMACOLOGICAL CORRECTION ENDOTHELIUM-ASSOCIATED PATHOLOGY. 2017.
18. Roya Jahangard, S.S.S.E., Akram Vatannejad, Reza Meshkani., Autophagy protects peripheral blood mononuclear cells from high glucose-induced inflammation and apoptosis. Acta Biochimica Iranica, 2023. 1(1): p. 40-49.
19. Liu, J., Y. Yoshida, and U. Yamashita, Suppressive effect of reactive oxygen species on CD40-induced B cell activation. FEBS Lett, 2007. 581(26): p. 5043-9.
20. El-Bahr, S.M., Effect of curcumin on hepatic antioxidant enzymes activities and gene expressions in rats intoxicated with aflatoxin B1. Phytother Res, 2015. 29(1): p. 134-40.
21. Yaser Mohassel , S.A., Shayan Mostafae , Mohammad Taghi Goodarzi Assessing the Possible Association between Polymorphism of C677T MTHFR with Preeclampsia Risk: A Systematic Review and Bayesian Hierarchical Meta-Analysis. Acta Biochimica Iranica, 2023. 1(1): p. 3-11.
22. Sattar Gorgani-Firuzjaee, R.M., Resveratrol reduces high glucose-induced de-novo lipogenesis through mTOR mediated induction of autophagy in HepG2 cells. Acta Biochimica Iranica, 2023. 1(1): p. 32-39.
23. Mishina, N.M., P.A. Tyurin-Kuzmin, K.N. Markvicheva, A.V. Vorotnikov, V.A. Tkachuk, V. Laketa, et al., Does cellular hydrogen peroxide diffuse or act locally? Antioxid Redox Signal, 2011. 14(1): p. 1-7.
24. Eyries, M., T. Collins, and L.M. Khachigian, Modulation of growth factor gene expression in vascular cells by oxidative stress. Endothelium, 2004. 11(2): p. 133-9.
25. Morikawa, M., R. Derynck, and K. Miyazono, TGF-β and the TGF-β Family: Context-Dependent Roles in Cell and Tissue Physiology. Cold Spring Harb Perspect Biol, 2016. 8(5).
26. Shin, H., H.G. Yoo, S. Inui, S. Itami, I.G. Kim, A.R. Cho, et al., Induction of transforming growth factor-beta 1 by androgen is mediated by reactive oxygen species in hair follicle dermal papilla cells. BMB Rep, 2013. 46(9): p. 460-4.
27. Sintara, K., D. Thong-Ngam, S. Patumraj, N. Klaikeaw, and T. Chatsuwan, Curcumin suppresses gastric NF-kappaB activation and macromolecular leakage in Helicobacter pylori-infected rats. World J Gastroenterol, 2010. 16(32): p. 4039-46.
28. Bhaskar, S., P.R. Sudhakaran, and A. Helen, Quercetin attenuates atherosclerotic inflammation and adhesion molecule expression by modulating TLR-NF-κB signaling pathway. Cell Immunol, 2016. 310: p. 131-140.
29. Lawrence, T., The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol, 2009. 1(6): p. a001651.
30. Yao, Q.Y., B.L. Xu, J.Y. Wang, H.C. Liu, S.C. Zhang, and C.T. Tu, Inhibition by curcumin of multiple sites of the transforming growth factor-beta1 signalling pathway ameliorates the progression of liver fibrosis induced by carbon tetrachloride in rats. BMC Complement Altern Med, 2012. 12: p. 156.
31. Gaedeke, J., N.A. Noble, and W.A. Border, Curcumin blocks multiple sites of the TGF-beta signaling cascade in renal cells. Kidney Int, 2004. 66(1): p. 112-20.
32. Dikshit, P., A. Goswami, A. Mishra, M. Chatterjee, and N.R. Jana, Curcumin induces stress response, neurite outgrowth and prevent NF-kappaB activation by inhibiting the proteasome function. Neurotox Res, 2006. 9(1): p. 29-37.
33. Samuhasaneeto, S., D. Thong-Ngam, O. Kulaputana, D. Suyasunanont, and N. Klaikeaw, Curcumin decreased oxidative stress, inhibited NF-kappaB activation, and improved liver pathology in ethanol-induced liver injury in rats. J Biomed Biotechnol, 2009. 2009: p. 981963.
| Files | ||
| Issue | Vol 1 No 2 (2023) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/abi.v1i2.14106 | |
| Keywords | ||
| Curcumin ransforming growth factor-β Antioxidants Oxidative stress nuclear factor κB | ||
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How to Cite
1.
Jafari-Hafshejani F, Shahanipour K, Kazemipiur M, Seif F, Jafari A, Noor Behbahani M, Babaahmadi-Rezaei H. Curcumin Attenuates Oxidative Stress-Induced Effects on TGF-β Expression and NF-κB Signaling in Bovine Aortic Endothelial Cells. ABI. 2023;1(2):90-95.
