Abstract
Background
Fucoidan, a polysaccharide derived from brown seaweed, has multiple biological properties, including antioxidant, antitumor, anticoagulant, and anti-inflammatory effects. However, there are few reports on their neuroprotective effects.
Objective
This study is about the neuroprotective effects of fucoidan against Aβ42-induced neuronal apoptosis in human neuroblastoma SH-SY5Y cells.
Methods
The protective effects of fucoidan against cell death by Aβ42 were measured with FDA/PI and Hoechst 33342 staining and immunoblotting about apoptosis-related proteins.
Results
In this study, fucoidan activated autophagy by regulating the expression of autophagy markers, significantly upregulating the Bcl-2/Bax ratio, and downregulating cleaved caspase-3/caspase-3. Moreover, fucoidan improved Aβ42-induced neuronal apoptosis by activating the phosphatidylinositol 3-kinase/protein kinase B signaling pathway and mitogen-activated protein kinase cascade in SH-SY5Y cells. Additionally, Hoechst 33342 staining showed that fucoidan diminished the level of the apoptotic nuclei in Aβ42-induced SH-SY5Ycells.
Conclusion
This study proposes fucoidan as a potential therapeutic candidate for AD treatment.
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Data availability
Not applicable.
References
Apostolova E, Lukova P, Baldzhieva A, Katsarov P, Nikolova M, Iliev I, Peychev L, Trica B, Oancea F, Delattre C, Kokova V (2020) Immunomodulatory and anti-inflammatory effects of fucoidan: a review. Polymers (basel) 12(10):2338. https://doi.org/10.3390/polym12102338
Blagov AV, Grechko AV, Nikiforov NG, Borisov EE, Sadykhov NK, Orekhov AN (2022) Role of impaired mitochondrial dynamics processes in the pathogenesis of Alzheimer’s disease. Int J Mol Sci 23(13):6954. https://doi.org/10.3390/ijms23136954
Carchman EH, Rao J, Loughran PA, Rosengart MR, Zuckerbraun BS (2011) Heme oxygenase-1-mediated autophagy protects against hepatocyte cell death and hepatic injury from infection/sepsis in mice. Hepatology 53(6):2053–2062. https://doi.org/10.1002/hep.24324
Chen GF, Xu TH, Yan Y, Zhou YR, Jiang Y, Melcher K, Xu HE (2017) Amyloid beta: structure, biology and structure-based therapeutic development. Acta Pharmacol Sin 38(9):1205–1235. https://doi.org/10.1038/aps.2017.28
Chun Y, Kim J (2018) Autophagy: an essential degradation program for cellular homeostasis and life. Cells 7(12):278. https://doi.org/10.3390/cells7120278
D’Amelio M, Cavallucci V, Cecconi F (2010) Neuronal caspase-3 signaling: not only cell death. Cell Death Differ 17(7):1104–1114. https://doi.org/10.1038/cdd.2009.180
DeTure MA, Dickson DW (2019) The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegener 14(1):32. https://doi.org/10.1186/s13024-019-0333-5
Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35(4):495–516. https://doi.org/10.1080/01926230701320337
Gorman AM (2008) Neuronal cell death in neurodegenerative diseases: recurring themes around protein handling. J Cell Mol Med 12(6A):2263–2280. https://doi.org/10.1111/j.1582-4934.2008.00402.x
Guo H, Cui H, Peng X, Fang J, Zuo Z, Deng J, Wang X, Wu B, Chen K, Deng J (2015) Modulation of the PI3K/Akt pathway and Bcl-2 family proteins involved in Chicken’s tubular apoptosis induced by nickel chloride (NiCl(2)). Int J Mol Sci 16(9):22989–23011. https://doi.org/10.3390/ijms160922989
Husni A, Izmi N, Ayunani FZ, Kartini A, Husnayain N, Isnansetyo A (2022) Characteristics and antioxidant activity of fucoidan from sargassum hystrix: effect of extraction method. Int J Food Sci 2022:3689724. https://doi.org/10.1155/2022/3689724
Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19(21):5720–5728. https://doi.org/10.1093/emboj/19.21.5720
Kwak JY (2014) Fucoidan as a marine anticancer agent in preclinical development. Mar Drugs 12(2):851–870. https://doi.org/10.3390/md12020851
Lacor PN, Buniel MC, Chang L, Fernandez SJ, Gong Y, Viola KL, Lambert MP, Velasco PT, Bigio EH, Finch CE, Krafft GA, Klein WL (2004) Synaptic targeting by Alzheimer’s-related amyloid beta oligomers. J Neurosci 24(45):10191–10200. https://doi.org/10.1523/JNEUROSCI.3432-04.2004
Lauretti E, Dincer O (1867) Pratico D (2020) Glycogen synthase kinase-3 signaling in Alzheimer’s disease. Biochim Biophys Acta Mol Cell Res 5:118664. https://doi.org/10.1016/j.bbamcr.2020.118664
Li N, Zhan X (2019) Mitochondrial dysfunction pathway networks and mitochondrial dynamics in the pathogenesis of pituitary adenomas. Front Endocrinol (lausanne) 10:690. https://doi.org/10.3389/fendo.2019.00690
Liu Y, Shi C, He Z, Zhu F, Wang M, He R, Zhao C, Shi X, Zhou M, Pan S, Gao Y, Li X, Qin R (2021) Inhibition of PI3K/AKT signaling via ROS regulation is involved in Rhein-induced apoptosis and enhancement of oxaliplatin sensitivity in pancreatic cancer cells. Int J Biol Sci 17(2):589–602. https://doi.org/10.7150/ijbs.49514
Long HZ, Cheng Y, Zhou ZW, Luo HY, Wen DD, Gao LC (2021) PI3K/AKT signal pathway: a target of natural products in the prevention and treatment of Alzheimer’s disease and Parkinson’s disease. Front Pharmacol 12:648636. https://doi.org/10.3389/fphar.2021.648636
Mattson MP (2000) Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol 1(2):120–130. https://doi.org/10.1038/35040009
Meng Y, Wang W, Kang J, Wang X, Sun L (2017) Role of the PI3K/AKT signalling pathway in apoptotic cell death in the cerebral cortex of streptozotocin-induced diabetic rats. Exp Ther Med 13(5):2417–2422. https://doi.org/10.3892/etm.2017.4259
Misrani A, Tabassum S, Yang L (2021) Mitochondrial dysfunction and oxidative stress in Alzheimer’s disease. Front Aging Neurosci 13:617588. https://doi.org/10.3389/fnagi.2021.617588
Murphy MP, LeVine H 3rd (2010) Alzheimer’s disease and the amyloid-beta peptide. J Alzheimers Dis 19(1):311–323. https://doi.org/10.3233/JAD-2010-1221
Park JM, Huang S, Wu TT, Foster NR, Sinicrope FA (2013) Prognostic impact of Beclin 1, p62/sequestosome 1 and LC3 protein expression in colon carcinomas from patients receiving 5-fluorouracil as adjuvant chemotherapy. Cancer Biol Ther 14(2):100–107. https://doi.org/10.4161/cbt.22954
Penalver R, Lorenzo JM, Ros G, Amarowicz R, Pateiro M, Nieto G (2020) Seaweeds as a Functional Ingredient for a Healthy Diet. Mar Drugs 18(6):301. https://doi.org/10.3390/md18060301
Pradhan B, Nayak R, Patra S, Bhuyan PP, Behera PK, Mandal AK, Behera C, Ki JS, Adhikary SP, MubarakAli D, Jena M (2022) A state-of-the-art review on fucoidan as an antiviral agent to combat viral infections. Carbohydr Polym 291:119551. https://doi.org/10.1016/j.carbpol.2022.119551
Razani E, Pourbagheri-Sigaroodi A, Safaroghli-Azar A, Zoghi A, Shanaki-Bavarsad M, Bashash D (2021) The PI3K/Akt signaling axis in Alzheimer’s disease: a valuable target to stimulate or suppress? Cell Stress Chaperones 26(6):871–887. https://doi.org/10.1007/s12192-021-01231-3
Roux PP, Blenis J (2004) ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev 68(2):320–344. https://doi.org/10.1128/MMBR.68.2.320-344.2004
Shamas-Din A, Kale J, Leber B, Andrews DW (2013) Mechanisms of action of Bcl-2 family proteins. Cold Spring Harb Perspect Biol 5(4):a008714. https://doi.org/10.1101/cshperspect.a008714
Song G, Li Y, Lin L, Cao Y (2015) Anti-autophagic and anti-apoptotic effects of memantine in a SH-SY5Y cell model of Alzheimer’s disease via mammalian target of rapamycin-dependent and-independent pathways. Mol Med Rep 12(5):7615–7622. https://doi.org/10.3892/mmr.2015.4382
Swerdlow RH (2011) Brain aging, Alzheimer’s disease, and mitochondria. Biochim Biophys Acta 1812(12):1630–1639. https://doi.org/10.1016/j.bbadis.2011.08.012
Swerdlow RH (2018) Mitochondria and mitochondrial cascades in Alzheimer’s disease. J Alzheimers Dis 62(3):1403–1416. https://doi.org/10.3233/JAD-170585
Tamagno E, Guglielmotto M, Vasciaveo V, Tabaton M (2021) Oxidative stress and beta amyloid in Alzheimer’s disease. Which comes first: the chicken or the egg? Antioxidants (basel) 10(9):1479. https://doi.org/10.3390/antiox10091479
Tanabe F, Yone K, Kawabata N, Sakakima H, Matsuda F, Ishidou Y, Maeda S, Abematsu M, Komiya S, Setoguchi T (2011) Accumulation of p62 in degenerated spinal cord under chronic mechanical compression: functional analysis of p62 and autophagy in hypoxic neuronal cells. Autophagy 7(12):1462–1471. https://doi.org/10.4161/auto.7.12.17892
Thorburn A (2008) Apoptosis and autophagy: regulatory connections between two supposedly different processes. Apoptosis 13:1–9. https://doi.org/10.1007/s10495-007-0154-9
Ushakova NA, Morozevich GE, Ustyuzhanina NE, Bilan MI, Usov AI, Nifantiev NE, Preobrazhenskaya ME (2009) Anticoagulant activity of fucoidans from brown algae. Biochem Moscow Suppl Ser B Biomed Chem 3(1):77–83. https://doi.org/10.1134/s1990750809010119
Wang X, Wang W, Li L, Perry G, Lee HG, Zhu X (2014) Zhu X (2014) Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease. Biochim Biophys Acta 1842(8):1240–1247. https://doi.org/10.1016/j.bbadis.2013.10.015
Wijesekara I, Pangestuti R, Kim S-K (2011) Biological activities and potential health benefits of sulfated polysaccharides derived from marine algae. Carbohydr Polym 84(1):14–21. https://doi.org/10.1016/j.carbpol.2010.10.062
Yao M, Nguyen TV, Pike CJ (2005) Beta-amyloid-induced neuronal apoptosis involves c-Jun N-terminal kinase-dependent downregulation of Bcl-w. J Neurosci 25(5):1149–1158. https://doi.org/10.1523/JNEUROSCI.4736-04.2005
Zhang M, Sun L, Gong X, Yao H (2019) Effects of PI3K/Akt signaling pathway on serum C-reactive protein, serum amyloid A and cognitive dysfunction in mice with Alzheimer’s disease. Int J Clin Exp Med 12(12):13437–13445
Zorov DB, Juhaszova M, Sollott SJ (2014) Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 94(3):909–950. https://doi.org/10.1152/physrev.00026.2013
Acknowledgements
We wish to thank Dr. Jihee Choi for helping start this experiment and publish it.
Funding
This research was supported by the Korea Institute of Marine Science and Technology Promotion (KIMST) funded by the Ministry of Oceans and Fisheries, Republic of Korea (20220128), and by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (IPET) through High Value‐Added Food Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA) (grant number 321024‐04‐1‐HD020).
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Investigation and data organization, CWK; original draft preparation, visualization, and writing, CWK; review and editing, MP and HJL; conceptualization and supervision, MP and HJL All authors have read and agreed to the published version of the manuscript.
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Author Chae-Won Kang declares that she has no conflict of interest in this study. Author Miey Park declares that she has no conflict of interest in this study. Author Hae-Jeung Lee declares that she has no conflicts of interest in this study.
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Kang, CW., Park, M. & Lee, HJ. Fucoidan ameliorates amyloid-β 42 oligomer-induced neuronal apoptosis by activating the PI3K/Akt signaling pathway and MAPK cascades in human neuroblastoma SH-SY5Y cells. Mol. Cell. Toxicol. (2023). https://doi.org/10.1007/s13273-023-00401-x
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DOI: https://doi.org/10.1007/s13273-023-00401-x