Fucoidan reduces oxidative stress by regulating the gene expression of HO‑1 and SOD‑1 through the Nrf2/ERK signaling pathway in HaCaT cells

Ryu,Min Ju; Chung,Ha Sook

doi:10.3892/mmr.2016.5623

Fucoidan reduces oxidative stress by regulating the gene expression of HO‑1 and SOD‑1 through the Nrf2/ERK signaling pathway in HaCaT cells

Authors:
- Min Ju Ryu
- Ha Sook Chung
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Affiliations: Department of Food and Nutrition, College of Natural Sciences, Duksung Women's University, Seoul 01369, Republic of Korea
Published online on: August 11, 2016 https://doi.org/10.3892/mmr.2016.5623
Pages: 3255-3260

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Abstract

Fucoidan, a sulfated polysaccharide, is found in edible brown algae. In the present study, the molecular mechanisms of fucoidan against mild oxidative stress in human keratinocytes were investigated. The current study indicated that fucoidan significantly augmented the antioxidants heme oxygenase‑1 (HO‑1) and superoxide dismutase‑1 (SOD‑1) via the upregulation of nuclear factor erythroid 2‑related factor 2 (Nrf2) and markedly reduced the cytoplasmic stability of kelch‑like ECH‑associated protein 1. The upregulation of HO‑1 and SOD‑1 detected in the fucoidan‑treated cells may be responsible for the increased resistance to mild oxidative stress, indicating that fucoidan may augment the activities of antioxidant enzymes via stimulating Nrf2. This is the first report, to the best of our knowledge, to demonstrate that fucoidan attenuates oxidative stress by regulating the gene expression of SOD‑1 and HO‑1 via the Nrf2/extracellular signal‑regulated kinase signaling pathway.

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1	Patankar MS, Oehninger S, Barnett T, Williams RL and Clark GF: A revised structure for fucoidan may explain some of its biological activities. J Biol Chem. 268:21770–21776. 1993.PubMed/NCBI
2	Durig J, Bruhn T, Zurborn KH, Gutensohn K, Bruhn HD and Béress L: Anticoagulant fucoidan fractions from Fucus vesiculosus induce platelet activation in vitro. Thromb Res. 85:479–491. 1997. View Article : Google Scholar : PubMed/NCBI
3	Soeda S, Kozako T, Iwata K and Shimeno H: Oversulfated fucoidan inhibits the basic fibroblast growth factor-induced tube formation by human umbilical vein endothelial cells: Its possible mechanism of action. Biochim Biophys Acta. 1497:127–134. 2000. View Article : Google Scholar : PubMed/NCBI
4	Teruya T, Konishi T, Uechi S, Tamaki H and Tako M: Anti-proliferative activity of oversulfated fucoidan from commercially cultured Cladosiphon okamuranus TOKIDA in U937 cells. Int J Biol Macromol. 41:221–226. 2007. View Article : Google Scholar : PubMed/NCBI
5	Thompson KD and Dragar C: Antiviral activity of Undaria pinnatifida against herpes simplex virus. Phytotherapy Res. 18:551–555. 2004. View Article : Google Scholar
6	Cumashi A, Ushakova NA, Preobrazhenskaya ME, D'Incecco A, Piccoli A, Totani L, Tinari N, Morozevich GE, Berman AE, Bilan MI, et al: A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic and antiadhesive activities of nine different fucoidans from brown seaweeds. Glycobiol. 17:541–552. 2007. View Article : Google Scholar
7	Maruyama H, Tamauchib H, Hashimotoc M and Nakano T: Suppression of Th2 immune responses by Mekabu fucoidan from Undaria pinnatifida Sporophylls. Int Arch Allergy Immunol. 137:289–294. 2005. View Article : Google Scholar : PubMed/NCBI
8	Yang JW, Yoon SY, Oh SJ, Kim SK and Kang KW: Biofunctional effects of fucoidan on the expression of inducible nitric oxide synthase. Biochem Biophys Res. 346:345–350. 2006. View Article : Google Scholar
9	Do H, Kang NS, Pyo SK, Billiar TR and Sohn EH: Differential regulation by fucoidan of IFN-γ-induced NO production in glial cells and macrophages. J Cell Biochem. 111:1337–1345. 2010. View Article : Google Scholar : PubMed/NCBI
10	Lee SH, Ko CL, Jee Y, Jeong Y, Kim M, Kim JS and Jeon YJ: Anti-inflammatory effect of fucoidan extracted from Ecklonia cava in zebrafish model. Carbohydr Polym. 92:84–89. 2013. View Article : Google Scholar
11	Zhang H, Teruya K, Eto H and Shirahata S: Fucoidan extract induces apoptosis in MCF-7 cells via a mechanism involving the ROS-dependent JNK activation and mitochondria-mediated pathways. PLoS One. 6:e274412011. View Article : Google Scholar : PubMed/NCBI
12	Matsumoto S, Nagaoka M, Hara T, Kimura-Takagi I, Mistuyama K and Ueyama S: Fucoidan derived from Cladosiphon okamuranus Tokida ameliorates murine chronic colitis through the down-regulation of Interleukin-6 production on colonic epithelial cells. Clin Exp Immunol. 136:432–439. 2004. View Article : Google Scholar : PubMed/NCBI
13	Carmichael J, DeGraff WG, Gazdar AF, Minna JD and Mitchell JB: Evaluation of a tetrazolium-based semiautomated colorimetric assay: Assessment of chemosensitivity testing. Cancer Res. 47:936–942. 1987.PubMed/NCBI
14	Ryu MJ, Kim AD, Kang KA, Chung HS, Suh IS, Chang WY and Hyun JW: The green algae Ulva fasciata Delile extract induces apoptotic cell death in human colon cancer cells. In Vitro Cell Dev Biol Anim. 49:74–81. 2013. View Article : Google Scholar : PubMed/NCBI
15	Ryu MJ, Kang KA, Piao MJ, Kim KC, Zheng J, Yao CW, Cha JW, Chung HS, Kim SC, Jung E, et al: 7,8-Dihydroxyflavone protects human keratinocytes against oxidative stress-induced cell damage via the ERK and PI3K/Akt-mediated Nrf2/HO-1 signaling pathways. Int J Mol Med. 33:964–970. 2014.PubMed/NCBI
16	Kim KC, Lee IK, Kang KA, Piao MJ, Ryu MJ, Kim JM, Lee NH and Hyun JW: Triphlorethol-A from Ecklonia cava up-regulates the oxidant sensitive 8-oxoguanine DNA glycosylase 1. Mar Drugs. 12:5357–5371. 2014. View Article : Google Scholar : PubMed/NCBI
17	Kundu J, Kim DH, Kundu JK and Chun KS: Thymoquinone induces heme oxygenase-1 expression in HaCaT cells via Nrf2/ARE activation: Akt and AMPKα as upstream targets. Food Chem Toxicol. 65:18–26. 2014. View Article : Google Scholar
18	Dinkova-Kostova AT, Holtzclaw WD, Cole RN, Itoh K, Wakabayashi N, Katoh Y, Yamamoto M and Talalay P: Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proc Natl Acad Sci USA. 99:11908–11913. 2002. View Article : Google Scholar : PubMed/NCBI
19	Wakabayashi N, Dinkova-Kostova AT, Holtzclaw WD, Kang MI, Kobayashi A, Yamamoto M, Kensler TW and Talalay P: Protection against electrophile and oxidant stress by induction of the phase 2 response: Fate of cysteines of the Keap1 sensor modified by inducers. Proc Natl Acad Sci USA. 101:2040–2045. 2004. View Article : Google Scholar : PubMed/NCBI
20	Li X and Darzynkiewicz Z: Cleavage of poly(ADP-ribose) polymerase measured in situ in individual cells: Relationship to DNA fragmentation and cell cycle position during apoptosis. Exp Cell Res. 255:125–132. 2000. View Article : Google Scholar : PubMed/NCBI
21	Yu R, Chen C, Mo YY, Hebbar V, Owuor ED, Tan TH and Kong AN: Activation of mitogen-activated protein kinase pathways induces antioxidant reponse element-mediated gene expression via a Nrf2-dependent mechanism. J Biol Chem. 275:39907–39913. 2000. View Article : Google Scholar : PubMed/NCBI
22	Boukamp P, Petrussevska RT, Breitkreutz D, Hornung J, Markham A and Fusenig NE: Normal keratinization in a spontaneously immortalized aneuploidy human keratinocyte cell line. J Cell Biol. 106:761–771. 1998. View Article : Google Scholar
23	Baraun S, Hanselmann C, Gassmann MG, auf dem Keller U, Born-Berclaz C, Chan K, Kan YW and Werner S: Nrf2 transcription factor, a novel target of keratinocyte growth factor action which regulates gene expression and inflammation in the healing skin wound. Mol Cell Biol. 22:5492–5505. 2002. View Article : Google Scholar
24	Jain AK, Mahajan S and Jaiswal AK: Phosphorylation and dephosphorylation of tyrosine 141 regulate stability and degradation of INrf2: A novel mechanism in Nrf2 activation. J Biol Chem. 283:17712–17720. 2008. View Article : Google Scholar : PubMed/NCBI
25	Lee OH, Jain AK, Papusha V and Jaiswal AK: An auto-regulatory loop between stress sensors INrf2 and Nrf2 controls their cellular abundance. J Biol Chem. 282:36412–36420. 2007. View Article : Google Scholar : PubMed/NCBI
26	Cullinan SB and Diehl JA: PERK-dependent activation of Nrf2 contributes to reox homeostasis and cell survival following endoplasmic reticulum stress. J Biol Chem. 279:20108–20117. 2004. View Article : Google Scholar : PubMed/NCBI