Abstract
Alginate oligosaccharide (AOS) was reported to possess antioxidant and free radical scavenging activities, but the specific effects and mechanisms remain unclear. We investigated the effects of AOS on H2O2-induced oxidative stress and apoptosis in human umbilical vein endothelial cells (HUVECs) and the associated mechanisms. HUVECs were treated with 100–800 µM hydrogen peroxide (H2O2) for various periods (12, 24, and 36 h) to establish an in vitro oxidative stress and apoptosis HUVEC model. AOS protects HUVEC cells against oxidative stress-induced apoptosis by decreasing the expression levels of caspase 3 and Bax, and increasing Bcl-2 expression. Microarray assay, real-time PCR and western blot results revealed that AOS was able to effectively suppress H2O2-induced apoptosis via regulated integrin-α/FAK/PI3K pathway by influencing the expression of integrin-α, FAK, PI3K, PTEN, P21, and CDK2. In conclusion, our study suggests that AOS can protect endothelial cells against oxidative stress injury caused by H2O2, providing novel alternative strategies to prevent atherosclerosis in the future.
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References
Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C et al (2017) Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation 135(10):e146–e603
Di B, Griendling KK (2015) Regulation of signal transduction by reactive oxygen species in the cardiovascular system. Circ Res 116(3):531–549
Dimmeler S, Haendeler J, Zeiher AM (2002) Regulation of endothelial cell apoptosis in atherothrombosis. Curr Opin Lipidol 13(5):531–536
Falk E (2006) Pathogenesis of atherosclerosis. J Am Coll Cardiol 47(8 Suppl):C7–C12
Guan JL (2010) Integrin signaling through FAK in the regulation of mammary stem cells and breast cancer. IUBMB Life 62(4):268–276
Guo JJ, Ma LL, Shi HT, Zhu JB, Wu J, Ding ZW, An Y, Zou YZ, Ge JB (2016) Alginate oligosaccharide prevents acute doxorubicin cardiotoxicity by suppressing oxidative stress and endoplasmic reticulum-mediated apoptosis. Mar Drugs 14(12):231–243
Guo J-J, Xu F-Q, Li Y-H, Li J, Liu X, Wang X-F, Hu L-G, An Y (2017) Alginate oligosaccharide alleviates myocardial reperfusion injury by inhibiting nitrative and oxidative stress and endoplasmic reticulum stress-mediated apoptosis. Drug Des Dev Ther 11:2387–2397
Liochev SI (2013) Reactive oxygen species and the free radical theory of aging. Free Radic Biol Med 60:1–4
Matter ML, Ruoslahti E (2001) A signaling pathway from the α5β1 and αvβ3 integrins that elevates bcl-2 transcription. J Biol Chem 276(30):27757–27763
McCarthy NJ, Bennett MR (2000) The regulation of vascular smooth muscle cell apoptosis. Cardiovasc Res 45(3):747–755
Paoli P, Giannoni E, Chiarugi P (2013) Anoikis molecular pathways and its role in cancer progression. Biochim Biophys Acta (BBA) - Mol Cell Res 1833(12):3481–3498
Sandoo A, van Zanten JJ, Metsios GS, Carroll D, Kitas GD (2010) The endothelium and its role in regulating vascular tone. Open Cardiovasc Med J 4:302–312
Song Z, Liu Y, Hao B, Yu S, Zhang H, Liu D, Zhou B, Wu L, Wang M, Xiong Z et al (2014) Ginsenoside Rb1 prevents H2O2-induced HUVEC senescence by stimulating sirtuin-1 pathway. PLoS ONE 9(11):e112699
Tousoulis D, Psaltopoulou T, Androulakis E, Papageorgiou N, Papaioannou S, Oikonomou E, Synetos A, Stefanadis C (2015) Oxidative stress and early atherosclerosis: novel antioxidant treatment. Cardiovasc Drugs Ther 29(1):75–88
Tusi SK, Khalaj L, Ashabi G, Kiaei M, Khodagholi F (2011) Alginate oligosaccharide protects against endoplasmic reticulum- and mitochondrial-mediated apoptotic cell death and oxidative stress. Biomaterials 32(23):5438–5458
Ueno M, Tamura Y, Toda N, Yoshinaga M, Terakado S, Otsuka K, Numabe A, Kawabata Y, Murota I, Sato N et al (2012) Sodium alginate oligosaccharides attenuate hypertension in spontaneously hypertensive rats fed a low-salt diet. Clin Exp Hypertens 34(5):305–310
Wang P, Jiang X, Jiang Y, Hu X, Mou H, Li M, Guan H (2007) In vitro antioxidative activities of three marine oligosaccharides. Nat Prod Res 21(7):646–654
Wang Y, Han F, Hu B, Li J, Yu W (2006) In vivo prebiotic properties of alginate oligosaccharides prepared through enzymatic hydrolysis of alginate. Nutr Res 26(11):597–603
Zuluaga M, Barzegari A, Letourneur D, Gueguen V, Pavon-Djavid G (2017) Oxidative stress regulation on endothelial cells by hydrophilic astaxanthin complex: chemical, biological, and molecular antioxidant activity evaluation. Oxid Med Cell Longev. https://doi.org/10.1155/2017/8073798
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This work was supported by the Grant from the National Natural Science Foundation of China (No. 31571829).
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JZ YH carried out experimental studies. JZ ZQW and RZ drafted the manuscript. YJM GMW participated in the design of the study and performed the statistical analysis. JZ YJM conceived of the study. All authors read and approved the final manuscript.
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Zhao, J., Han, Y., Wang, Z. et al. Alginate oligosaccharide protects endothelial cells against oxidative stress injury via integrin-α/FAK/PI3K signaling. Biotechnol Lett 42, 2749–2758 (2020). https://doi.org/10.1007/s10529-020-03010-z
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DOI: https://doi.org/10.1007/s10529-020-03010-z