Abstract
Inflammation induces pancreatic islet cell apoptosis. Effects of fucoidan from Acaudina molpadioides (Am-FUC) on inhibition of pancreatic islet cell apoptosis and inflammation in type 2 diabetic mice were investigated. Am-FUC repaired pancreatic islet cells, decreased serum C-reactive protein (CRP), macrophage inflammatory protein 1 (MIP-1), interleukin 1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) levels, and increased the IL-10 level. Am-FUC also reduced TNF-α, CRP, MIP-1, IL-1β, and IL-6 mRNA expressions, and increased IL-10 mRNA expression in epididymal adipose tissues. Am-FUC reduced Bid, Bax, cytochrome c, caspase 9, and caspase 3 mRNA expressions, and increased Bcl-2 and Bcl-xL mRNA expressions. Am-FUC down-regulated t-Bid, Bax, cytochrome c, and caspase 9 activities, cleaved caspase 3 proteins, and up-regulated Bcl-2 and Bcl-xL proteins. Thus, an Am-FUCblocked mitochondrial pathway was the suppression mechanism in pancreatic islet cell apoptosis via regulation of inflammatory cytokines providing dietary intervention in type 2 diabetes and inflammation-induced pancreatic islet apoptosis.
Keywords: fucoidan, apoptosis, inflammatory cytokine, pancreatic islet, Acaudina molpadioides
References
- 1.Muoio DM, Newgard CB. Mechanisms of disease: Molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes. Nat. Rev. Mol. Cell Bio. 2008;9:193–205. doi: 10.1038/nrm2327. [DOI] [PubMed] [Google Scholar]
- 2.Moon H, Chon J, Joo J, Kim D, In J, Lee H, Park J, Choi J. FTY720 preserved islet β-cell mass by inhibiting apoptosis and increasing survival of β-cells in db/db mice. Diabetes Metab. Res. 2013;29:19–24. doi: 10.1002/dmrr.2341. [DOI] [PubMed] [Google Scholar]
- 3.El-Azab MF, Attia FM, El-Mowafy AM. Novel role of curcumin combined with bone marrow transplantation in reversing experimental diabetes: Effects on pancreatic islet regeneration, oxidative stress, and inflammatory cytokines. Eur. J. Pharmacol. 2011;658:41–48. doi: 10.1016/j.ejphar.2011.02.010. [DOI] [PubMed] [Google Scholar]
- 4.Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabete. 2003;52:102–110. doi: 10.2337/diabetes.52.1.102. [DOI] [PubMed] [Google Scholar]
- 5.Hou G, Li C, Liu S, Huan Y, Liu Q, Sun S, Li L, Hou S, Shen Z. Long-term treatment with EXf, a peptide analog of Exendin-4, improves β-cell function and survival in diabetic KKAy mice. Peptide. 2013;40:123–132. doi: 10.1016/j.peptides.2013.01.010. [DOI] [PubMed] [Google Scholar]
- 6.Kang JH, Tsuyoshi G, Han IS, Kawada T, Kim YM, Yu R. Dietary capsaicin reduces obesity-induced insulin resistance and hepatic steatosis in obese mice fed a high-fat diet. Obesit. 2010;18:780–787. doi: 10.1038/oby.2009.301. [DOI] [PubMed] [Google Scholar]
- 7.Bouzakri K, Plomgaard P, Berney T, Donath MY, Pedersen BK, Halban PA. Bimodal effect on pancreatic β-cells of secretory products from normal or insulin-resistant human skeletal muscle. Diabete. 2011;60:1111–1121. doi: 10.2337/db10-1178. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Zhang Z, Dign Y, Dai X, Wang J, Li Y. Epigallocatechin-3-gallate protects proinflammatory cytokine induced injuries in insulin-producing cells through the mitochondrial pathway. Eur. J. Pharmacol. 2011;670:311–316. doi: 10.1016/j.ejphar.2011.08.033. [DOI] [PubMed] [Google Scholar]
- 9.Kara G, Cifcibasi E, Karsidag K, Cintan S. Short term effects of periodontal therapy on inflammatory markers in patients with type-2 diabetes. Saudi Med. J. 2015;36:469–476. doi: 10.15537/smj.2015.4.10380. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Chaurio RA, Janko C, Muñoz LE, Frey B, Herrmann M, Gaipl US. Phospholipids: Key players in apoptosis and immune regulation. Molecule. 2009;14:4892–4914. doi: 10.3390/molecules14124892. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Wilding JP. The importance of free fatty acids in the development of type 2 diabetes. Diabetic Med. 2007;24:934–945. doi: 10.1111/j.1464-5491.2007.02186.x. [DOI] [PubMed] [Google Scholar]
- 12.Daniele G, Eldor R, Merovic A, Clarke GD, Xiong J, Tripathy D, Taranova A, Abdul-Ghani M, De Fronzo RA. Chronic reduction of plasma free fatty acid improves mitochondrial function and whole-body insulin sensitivity in obese and type 2 diabetic individuals. Diabete. 2014;63:2812–2820. doi: 10.2337/db13-1130. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Hu S, Chang Y, Wang J, Xue C, Shi D, Xu H, Wang Y. Fucosylated chondroitin sulfate from Acaudina molpadioides improves hyperglycemia via activation of PKB/GLUT4 signaling in skeletal muscle of insulin resistant mice. Food Funct. 2013;4:1639–1646. doi: 10.1039/c3fo60247h. [DOI] [PubMed] [Google Scholar]
- 14.Yu L, Ge L, Xue C, Chang Y, Zhang C, Xu X, Wang Y. Structural study of fucoidan from sea cucumber Acaudina molpadioides: A fucoidan containing novel tetrafucose repeating unit. Food Chem. 2014;142:197–200. doi: 10.1016/j.foodchem.2013.06.079. [DOI] [PubMed] [Google Scholar]
- 15.Chen S, Hu Y, Ye X, Li G, Yu G, Xue C, Chai W. Sequence determination and anticoagulant and antithrombotic activities of a novel sulfated fucan isolated from the sea cucumber Isostichopus badionotus. Biochim. Biophys. Act. 2012;1820:989–1000. doi: 10.1016/j.bbagen.2012.03.002. [DOI] [PubMed] [Google Scholar]
- 16.Zhang Y, Song S, Song D, Liang H, Wang W, Ji A. Proliferative effects on neural stem/progenitor cells of a sulfated polysaccharide purified from the sea cucumber Stichopus japonicus. J. Biosci. Bioeng. 2010;109:67–72. doi: 10.1016/j.jbiosc.2009.07.010. [DOI] [PubMed] [Google Scholar]
- 17.Kim MJ, Chang UJ, Lee JS. Inhibitory effects of Fucoidan in 3T3-L1 adipocyte differentiation. Mar. Biotechnol. 2009;11:557–562. doi: 10.1007/s10126-008-9170-1. [DOI] [PubMed] [Google Scholar]
- 18.Kariya Y, Mulloy B, Imai K, Tominaga A, Kaneko T, Asari A, Suzuki K, Masuda H, Kyogashima M, Ishii T. Isolation and partial characterization of fucan sulfates from the body wall of sea cucumber Stichopus japonicus and their ability to inhibit osteoclastogenesis. Carbohyd. Res. 2004;339:1339–1346. doi: 10.1016/j.carres.2004.02.025. [DOI] [PubMed] [Google Scholar]
- 19.Hu S, Xia G, Wang J, Wang Y, Li Z, Xue C. Fucoidan from sea cucumber protects against high-fat high-sucrose diet-induced hyperglycaemia and insulin resistance in mice. J. Funct. Food. 2014;10:128–138. doi: 10.1016/j.jff.2014.05.012. [DOI] [Google Scholar]
- 20.Gong L, Liu F, Wang J, Wang X, Hou X, Sun Y, Qin W, Wei S, Zhang Y, Chen L, Zhang M. Hyperglycemia induces apoptosis of pancreatic islet endothelial cells via reactive nitrogen species-mediated Jun N-terminal kinase activation. Biochim. Biophys. Act. 2011;1813:1211–1219. doi: 10.1016/j.bbamcr.2011.03.011. [DOI] [PubMed] [Google Scholar]
- 21.Allagnat F, Fukaya M, Nogueira TC, Delaroche D, Welsh N, Marselli L, Marchetti P, Haefliger JA, Haefliger JA, Eizirik DL, Cardozo AK. C/EBP homologous protein contributes to cytokine-induced pro-inflammatory responses and apoptosis in β-cells. Cell Death Differ. 2012;19:1836–1846. doi: 10.1038/cdd.2012.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Lin N, Chen H, Zhang H, Wan X, Su Q. Mitochondrial reactive oxygen species (ROS) inhibition ameliorates palmitate-induced INS-1 beta cell death. Endocrin. 2012;42:107–117. doi: 10.1007/s12020-012-9633-z. [DOI] [PubMed] [Google Scholar]
- 23.Natalicchio A, Stefano FD, Orlando MR, Melchiorre M, Leonardini A, Cignarelli A, Labarbuta R, Marchetti P, Perrini S, Laviola L, Giorgino F. Exendin-4 prevents c-Jun N-terminal protein kinase activation by tumor necrosis factor-α (TNFα) and inhibits TNFα-induced apoptosis in insulin-secreting cells. Endocrinolog. 2010;151:2019–2029. doi: 10.1210/en.2009-1166. [DOI] [PubMed] [Google Scholar]
- 24.Lei K, Nimnual A, Zong WX, Kennedy NJ, Flavell RA, Thompson CB, Bar-Saqi D, Davis RJ. The Bax subfamily of Bcl2-related proteins is essential for apoptotic signal transduction by c-Jun NH(2)-terminal kinase. Mol. Cell. Biol. 2002;22:4929–4942. doi: 10.1128/MCB.22.13.4929-4942.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.McKenzie MD, Jamieson E, Jansen ES, Scott CL, Huang DC, Bouillet P, Allison J, Kay TW, Strasser A, Thomas HE. Glucose induces pancreatic islet cell apoptosis that requires the BH3-only proteins Bim and Puma and multi-BH domain protein Bax. Diabete. 2010;59:644–652. doi: 10.2337/db09-1151. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Park H S, Hwang H J, Kim GY, Cha HJ, Kim WJ, Kim ND, Yoo YH, Choi YH. Induction of apoptosis by fucoidan in human leukemia U937 cells through activation of p38 MAPK and modulation of Bcl-2 family. Mar. Drug. 2013;11:2347–2364. doi: 10.3390/md11072347. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Bishayee K, Ghosh S, Mukherjee A, Sadhukhan R, Mondal J, Khuda-Bukhsh AR. Quercetin induces cytochrome-c release and ROS accumulation to promote apoptosis and arrest the cell cycle in G2/M, in cervical carcinoma: Signal cascade and drug-DNA interaction. Cell Proliferat. 2013;46:153–163. doi: 10.1111/cpr.12017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Jiang Y, Yang J, Yang C, Meng F, Zhou Y, Yu B, Khan M, Yang H. Vitamin K4 induces tumor cytotoxicity in human prostate carcinoma PC-3 cells via the mitochondria-related apoptotic pathway. Pharmazi. 2013;68:442–448. [PubMed] [Google Scholar]
- 29.Shamas-Din A, Bindner S, Zhu W, Zaltsman Y, Campbell C, Gross A, Leber B, Andrews DW, Fradin C. tBid undergoes multiple conformational changes at the membrane required for Bax activation. J. Biol. Chem. 2013;288:22111–22127. doi: 10.1074/jbc.M113.482109. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Santin I, Moore F, Colli ML, Gurzov EN, Marselli L, Marchetti P, Eizirik DL. PTPN2, a candidate gene for type 1 diabetes, modulates pancreatic β-cell apoptosis via regulation of the BH3-only protein Bim. Diabete. 2011;60:3279–3288. doi: 10.2337/db11-0758. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Xu X, Tu L, Jiang W, Feng W, Zhao C, Wang D. Bradykinin prevents the apoptosis of NIT-1 cells induced by TNF-a via the PI3K/Akt and MAPK signaling pathways. Int. J. Mol. Med. 2012;29:891–898. doi: 10.3892/ijmm.2012.922. [DOI] [PubMed] [Google Scholar]
- 32.Liou CM, Tsai SC, Kuo CH, Ting H, Lee SD. Cardiac Fas-dependent and mitochondria-dependent apoptosis after chronic cocaine abuse. Int. J. Mol. Sci. 2014;15:5988–6001. doi: 10.3390/ijms15045988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Brown JE, Dunmore SJ. Leptin decreases apoptosis and alters BCL-2: Bax ratio in clonal rodent pancreatic beta-cells. Diabetes Metab. Res. 2007;23:497–502. doi: 10.1002/dmrr.726. [DOI] [PubMed] [Google Scholar]
- 34.Sha H, Ma Q, Jha R, Xu F, Wang L, Wang Z, Zhao Y, Fan F. Resveratrol ameliorates hepatic injury via the mitochondrial pathway in rats with severe acute pancreatitis. Eur. J. Pharmacol. 2008;601:136–142. doi: 10.1016/j.ejphar.2008.10.017. [DOI] [PubMed] [Google Scholar]