title: Effects of low-level hexabromocyclododecane (HBCD) exposure on cardiac development in zebrafish embryos.
abstract: Hexabromocyclododecane (HBCD) is one of the most widely used brominated flame retardants. In the present study, zebrafish embryos were exposed to HBCD at the low concentrations of 0, 2, 20 and 200 nM. The results showed HBCD exposure resulted in an increase in heart rate and cardiac arrhythmia after exposure for 72 h, though the survival rate and the whole malformation rate were not significantly affected. These results demonstrated that the heart might be a target of HBCD. Low-level HBCD exposure may not share the same mechanisms as exposure to high concentrations, since no obvious increase of apoptotic cells around the heart was observed in the HBCD-treated groups. It was observed that the expression of Tbx5 and Nkx2.5 was significantly elevated by HBCD treatment in a dose-dependent manner using real-time quantitative PCR, which may be mainly responsible for the alteration of heart rate, given that Tbx5 and Nkx2.5 are two factors regulating ventricle conduction. The mRNA expression of RyR2 and Atp2a2b (SERCA2a) was up-regulated in the exposure group, which may be one of reasons to affect the normal heart rate, since SERCA2a and RyR2 play an important role in calcium ion transport of cadiomyocytes. However, HBCD exposure did not significantly change the expression of Actc1l, Tnnt2, and Myh6, which are mainly muscle contractile genes that play key roles in the formation of cardiac structure. These results were consistent with the lack of effect seen on the other measurements of cardiac function, end diastolic volume, end-systolic volume, stroke volume, and cardiac output.
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, People's Republic of China.
authors.forename: Meifang
authors.initials: M
authors.lastname: Wu
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Zuo
authors.forename: Bowen
authors.initials: B
authors.lastname: Li
authors.forename: Lixing
authors.initials: L
authors.lastname: Huang
authors.forename: Meng
authors.initials: M
authors.lastname: Chen
authors.forename: Chonggang
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D018376:Cardiovascular Abnormalities / Q000139:chemically induced / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005411:Flame Retardants; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D000072576:Homeobox Protein Nkx-2.5; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D020107:Troponin T / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D005411:Flame Retardants; D000072576:Homeobox Protein Nkx-2.5; D006842:Hydrocarbons, Brominated; C528182:Nkx2.5 protein, zebrafish; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; D014157:Transcription Factors; D020107:Troponin T; D029961:Zebrafish Proteins; C481025:myh6 protein, zebrafish; C480681:tnnt2a protein, zebrafish; C089796:hexabromocyclododecane; D053148:Caspase 3; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D018995:Myosin Heavy Chains
references.citation: Circ Res. 2009 Sep 25;105(7):620-30
references.pmid: 19797194
references.citation: J Gen Physiol. 2012 Aug;140(2):87-92
references.pmid: 22851673
references.citation: Reprod Toxicol. 2008 Apr;25(3):335-51
references.pmid: 18262388
references.citation: Mar Pollut Bull. 2001 Aug;42(8):656-66
references.pmid: 11525283
references.citation: J Biol Chem. 1992 Jul 15;267(20):14483-9
references.pmid: 1385815
references.citation: Nature. 2009 Jun 4;459(7247):708-11
references.pmid: 19396158
references.citation: Chemosphere. 2008 Mar;71(2):268-76
references.pmid: 17980898
references.citation: Am J Physiol. 1998 Oct;275(4):H1441-8
references.pmid: 9746495
references.citation: Aquat Toxicol. 2009 Jun 4;93(1):29-36
references.pmid: 19356805
references.citation: Environ Health Perspect. 2004 Jan;112(1):9-17
references.pmid: 14698924
references.citation: Environ Toxicol Pharmacol. 2006 May;21(3):317-22
references.pmid: 21783674
references.citation: Environ Sci Technol. 2005 Apr 1;39(7):1987-94
references.pmid: 15871228
references.citation: Chemosphere. 2012 May;87(7):703-8
references.pmid: 22273185
references.citation: Cardiovasc Res. 2012 Dec 1;96(3):372-80
references.pmid: 22869620
references.citation: Environ Sci Technol. 2004 Jan 1;38(1):93-6
references.pmid: 14740722
references.citation: Dev Genet. 1996;19(2):119-30
references.pmid: 8900044
references.citation: Nucleic Acids Res. 2002 May 1;30(9):e36
references.pmid: 11972351
references.citation: Chemosphere. 2008 Sep;73(2):203-8
references.pmid: 18514256
references.citation: Environ Sci Technol. 2004 Nov 1;38(21):5497-504
references.pmid: 15575264
references.citation: Toxicol Sci. 2006 Dec;94(2):281-92
references.pmid: 16984958
references.citation: Development. 2004 Aug;131(16):4107-16
references.pmid: 15289437
references.citation: Cardiovasc Res. 2008 Jul 1;79(1):97-108
references.pmid: 18343897
references.citation: Chemosphere. 2011 Mar;82(11):1662-8
references.pmid: 21111444
references.citation: Science. 1998 Jul 3;281(5373):108-11
references.pmid: 9651244
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17705-10
references.pmid: 16314582
references.citation: Aquat Toxicol. 2007 May 31;82(4):296-307
references.pmid: 17412433
references.citation: Environ Toxicol. 2009 Aug;24(4):334-42
references.pmid: 18767142
references.citation: Chemosphere. 2006 Jun;64(2):187-208
references.pmid: 16434081
references.citation: Sci Total Environ. 2011 Sep 1;409(19):4048-53
references.pmid: 21708397
references.citation: Curr Opin Neurol. 2007 Oct;20(5):583-9
references.pmid: 17885449
references.citation: Nat Genet. 2005 Apr;37(4):423-8
references.pmid: 15735645
references.citation: Dev Biol. 1999 Jul 1;211(1):100-8
references.pmid: 10373308
references.citation: Environ Int. 2003 Sep;29(6):841-53
references.pmid: 12850100
references.citation: Toxicology. 2006 Feb 1;218(2-3):229-36
references.pmid: 16325980
references.citation: Br Med Bull. 2001;59:193-210
references.pmid: 11756211
references.citation: Environ Pollut. 2006 Nov;144(1):238-47
references.pmid: 16504358
references.citation: Environ Toxicol Pharmacol. 2004 Apr;16(3):141-5
references.pmid: 21782700
references.citation: Environ Sci Technol. 2009 Jan 1;43(1):201-7
references.pmid: 19209607
references.citation: Circ J. 2010 Nov;74(11):2410-8
references.pmid: 20962418
references.citation: Chemosphere. 2012 Apr;87(4):369-75
references.pmid: 22209252
references.citation: Europace. 2012 May;14(5):724-33
references.pmid: 22094454
references.citation: Nat Genet. 2001 Jul;28(3):276-80
references.pmid: 11431700
references.citation: Dev Dyn. 1995 Jul;203(3):253-310
references.pmid: 8589427
references.citation: Dev Dyn. 2011 Dec;240(12):2634-45
references.pmid: 22072574
references.citation: Arch Toxicol. 2003 Feb;77(2):69-79
references.pmid: 12590358
references.citation: Cardiol Clin. 2008 Aug;26(3):381-403, vi
references.pmid: 18538186
references.citation: Cell. 2007 Jun 29;129(7):1365-76
references.pmid: 17604724
references.citation: J Cell Biochem. 2004 May 1;92(1):189-99
references.pmid: 15095414
references.citation: JAMA. 2002 Mar 13;287(10):1308-20
references.pmid: 11886323
references.citation: Microsc Res Tech. 2000 Sep 15;50(6):522-31
references.pmid: 10998641
references.citation: Int J Cardiol. 2011 Mar 17;147(3):e44-5
references.pmid: 19217179
references.citation: Reprod Toxicol. 2009 Dec;28(4):456-67
references.pmid: 19577631
references.citation: Anadolu Kardiyol Derg. 2007 Jul;7 Suppl 1:43-6
references.pmid: 17584678
references.citation: Neurochem Int. 2003 Sep-Oct;43(4-5):533-42
references.pmid: 12742101
references.citation: Anat Rec. 2001 Jul 1;263(3):307-13
references.pmid: 11455540
references.citation: Cell. 2004 Apr 30;117(3):373-86
references.pmid: 15109497
references.citation: Environ Toxicol Chem. 2004 Sep;23(9):2194-201
references.pmid: 15378997
references.citation: Comp Biochem Physiol B Biochem Mol Biol. 2003 Dec;136(4):731-42
references.pmid: 14662298
references.citation: Dev Biol. 2007 Nov 1;311(1):136-46
references.pmid: 17869237
references.citation: Eur Heart J. 2002 Jul;23(14):1118-24
references.pmid: 12090750