title: Selenium-enriched Spirulina protects INS-1E pancreatic beta cells from human islet amyloid polypeptide-induced apoptosis through suppression of ROS-mediated mitochondrial dysfunction and PI3/AKT pathway.
abstract: OBJECTIVE
  Human islet amyloid polypeptide (hIAPP) aggregation is linked to loss of pancreatic beta cells in type 2 diabetes, in part due to oxidative stress. Currently, little is known about the effects of selenium-enriched Spirulina on beta cells with the presence of hIAPP. In this study, INS-1E rat insulinoma cells were used as a model to evaluate in vitro protective effects of Se-enriched Spirulina extract (Se-SE) against hIAPP-induced cell death, as well as the underlying mechanisms.
  
  
  METHODS
  Flow cytometric analysis was used to evaluate cell apoptosis, mitochondrial membrane potential (ΔΨm) and ROS generation. Caspase activity was measured using a fluorometric method. Western blotting was applied to detect protein expression.
  
  
  RESULTS
  Our results showed that exposure of INS-1E cells to hIAPP resulted in cell viability loss, LDH release and appearance of sub-G peak. However, cytotoxicity of hIAPP was significantly attenuated by co-treatment with Se-SE. Se-SE also inhibited hIAPP-induced activation of caspase-3, -8 and -9. Additionally, hIAPP-induced accumulation of ROS and superoxide was suppressed by co-treatment with Se-SE. Moreover, Se-SE was able to prevent hIAPP-induced depletion of ΔΨm and intracellular ATP, reduction in mitochondrial mass, changes in the expression of Bcl-2 family members, release of mitochondrial apoptogenic factors. Furthermore, hIAPP-mediated AKT inhibition was restored by co-treatment with Se-SE.
  
  
  CONCLUSIONS
  Our results showed that Se-SE protects INS-1E cells from hIAPP-induced cell death through preventing ROS overproduction, mitochondrial dysfunction and modulating PI3K/AKT pathway.
authors.affiliation: College of Life Sciences and Technology, Jinan University, Guangzhou, China, fenling03@gmail.com.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Li
authors.forename: Yum-Shing
authors.initials: YS
authors.lastname: Wong
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.forename: Juliana C N
authors.initials: JC
authors.lastname: Chan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D006836:Hydro-Lyases / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D058228:Islet Amyloid Polypeptide / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020011:Protective Agents / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012643:Selenium / Q000494:pharmacology*; D015398:Signal Transduction; D053545:Spirulina; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D006836:Hydro-Lyases; D058228:Islet Amyloid Polypeptide; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020011:Protective Agents; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D012643:Selenium; D051028:bcl-2-Associated X Protein; C494828:Bax protein, rat; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; C506435:Casp9 protein, rat; C045581:lactate dehydratase
references.citation: Nat Rev Mol Cell Biol. 2006 Jul;7(7):517-28
references.pmid: 16829982
references.citation: Proc Natl Acad Sci U S A. 1987 Jun;84(11):3881-5
references.pmid: 3035556
references.citation: Invest Ophthalmol Vis Sci. 2011 Sep 01;52(10):7027-37
references.pmid: 21697135
references.citation: Bioresour Technol. 2006 Dec;97(18):2260-5
references.pmid: 16343896
references.citation: FEBS Lett. 2013 Apr 17;587(8):1106-18
references.pmid: 23380070
references.citation: Diabetologia. 2009 Apr;52(4):626-35
references.pmid: 19148619
references.citation: J Inorg Biochem. 2007 Mar;101(3):493-505
references.pmid: 17222910
references.citation: J Biol Chem. 1998 Jan 30;273(5):2926-30
references.pmid: 9446604
references.citation: Phytochemistry. 2006 Nov;67(22):2424-30
references.pmid: 16973186
references.citation: Diabetes. 2007 May;56(5):1324-32
references.pmid: 17353506
references.citation: Diabetes. 2008 Feb;57(2):348-56
references.pmid: 17977957
references.citation: PLoS One. 2007 Oct 24;2(10):e1066
references.pmid: 17957250
references.citation: Prim Care Diabetes. 2008 Jun;2(2):81-5
references.pmid: 18684427
references.citation: Int J Biochem Cell Biol. 2013 Oct;45(10):2288-301
references.pmid: 23845738
references.citation: Biochem Biophys Res Commun. 2000 Jan 19;267(2):619-25
references.pmid: 10631112
references.citation: Science. 2001 Jun 1;292(5522):1728-31
references.pmid: 11387480
references.citation: Curr Pharm Biotechnol. 2008 Oct;9(5):400-5
references.pmid: 18855693
references.citation: J Cell Mol Med. 2009 Jul;13(7):1321-35
references.pmid: 18466357
references.citation: Int J Biochem Cell Biol. 2011 Apr;43(4):525-34
references.pmid: 21163363
references.citation: Int J Biochem Cell Biol. 2009 Mar;41(3):666-76
references.pmid: 18718551
references.citation: FEBS Lett. 2013 Apr 17;587(8):1119-27
references.pmid: 23337872
references.citation: Biochim Biophys Acta. 2009 May;1787(5):402-13
references.pmid: 18848916
references.citation: Int J Biochem Cell Biol. 2006;38(5-6):726-36
references.pmid: 16459127
references.citation: Eur J Clin Invest. 2004 Jul;34(7):475-81
references.pmid: 15255784
references.citation: Diabetes. 2003 Nov;52(11):2759-66
references.pmid: 14578294
references.citation: Nat Med. 2001 Oct;7(10):1133-7
references.pmid: 11590437
references.citation: FEBS J. 2006 Aug;273(15):3614-24
references.pmid: 16884500
references.citation: Biochim Biophys Acta. 2006 May-Jun;1757(5-6):509-17
references.pmid: 16829228
references.citation: J Integr Plant Biol. 2008 Jan;50(1):40-8
references.pmid: 18666950
references.citation: J Am Coll Nutr. 2005 Aug;24(4):250-6
references.pmid: 16093402
references.citation: Arch Toxicol. 2012 Feb;86(2):275-84
references.pmid: 21964636
references.citation: PLoS One. 2013 Aug 13;8(8):e68703
references.pmid: 23967052
references.citation: J Agric Food Chem. 2008 Jun 25;56(12):4352-8
references.pmid: 18522403
references.citation: Life Sci. 2001 Jul 20;69(9):1029-37
references.pmid: 11508645
references.citation: Cell Mol Life Sci. 2008 Sep;65(17):2763-75
references.pmid: 18661100
references.citation: Diabetes. 1991 Dec;40(12):1675-8
references.pmid: 1756907
references.citation: Biochim Biophys Acta. 2004 Mar 2;1688(2):95-101
references.pmid: 14990339
references.citation: J Med Food. 2001 Winter;4(4):193-199
references.pmid: 12639401
references.citation: Cell. 1993 Aug 27;74(4):609-19
references.pmid: 8358790
references.citation: J Nutr Biochem. 2006 Aug;17(8):548-60
references.pmid: 16443359
references.citation: Arch Toxicol. 2011 Apr;85(4):315-26
references.pmid: 20857089
references.citation: Endocr Rev. 2008 May;29(3):303-16
references.pmid: 18314421
references.citation: Int J Biochem Cell Biol. 2009 Jul;41(7):1526-35
references.pmid: 19166964
references.citation: Lancet. 2000 Jul 15;356(9225):233-41
references.pmid: 10963212
references.citation: Annu Rev Pharmacol Toxicol. 2007;47:143-83
references.pmid: 17029566
references.citation: Trends Endocrinol Metab. 2009 Jul;20(5):243-51
references.pmid: 19541499
references.citation: Diabetologia. 2000 Jun;43(6):687-95
references.pmid: 10907112