以秀丽隐杆线虫(C.elegans)为模型,本文研究了全氟辛烷磺酸(PFOS)对机体寿长的影响及初步机理.结果显示0.2~200 μmol/L的PFOS暴露50 h导致野生型秀丽线虫寿长呈剂量依赖性缩短.在4类转基因线虫上,观察到Insulin/IGF-l.1信号通路(IIS)相关的daf-16、daf-2和age-1基因突变或敲除能影响线虫的寿长.进一步观察PFOS暴露导致4类转基因线虫的寿长变化率,并与野生型线虫比较.在CF1139和CF1580突变种上daf16或daf2的突变均未改变PFOS的缩短寿长效应.而在CF1295和TJ1052转基因型上发现daf-16b的基因敲除或age-1基因突变阻断PFOS的减寿效应.结果表明PFOS慢性暴露能加速动物衰老,缩短寿长.PFOS作用与IIS信号通路关系密切,daf-16b和age-1基因在其中起重要作用.
Using a model of C.elegans, this study aims to investigate the effect of PFOS on the lifespan and its mechanisms. Results showed that 0.2~200 μmol/L PFOS shortened the lifespan of wild type wormsin a concentrationdependent manner after 50 h exposure.In four transgenic strains, mutation of daf-16, daf-2 and age-1 which are related to Insulin/IGFl.1pathway(IIS), could affect the lifespans of nematodes. We further observed lifespan change rates of the four transgene C.elegansafter exposed to PFOS.Results showed that mutation of daf-16 or daf-2 did not alter PFOS induced effects of shortening lifespan in CF1139 and CF1580 strain.However, knockout of daf-16b or mutation of age-1blocked PFOS induced effects of shortening lifespan in CF1295 and TJ1052 strain. Our results suggested that PFOS could accelerate aging and shorten the lifespan of nematodes. PFOSinduced effects are closely relative with IIS signaling pathways, in which daf-16b and age-1 play important roles.
[1]BUTENHOFF J L, OLSEN G W, PFAHLESHUTCHENS A. The applicability of biomonitoring data for perfluorooctanesulfonate to the environmental public health continuum[J]. Environ Health Perspect,2006, 114(11): 17761782.
[2]HOUDE M, MARTIN J W, LETCHER R J, et al. Biological monitoring of polyfluoroalkylsubstances: a review[J]. Environ Sci & Technol, 2006, 40(11): 34633473.
[3]刘薇,金一和,全燮,等. 沈阳市降雪中PFOS和PFOA污染现状调查[J]. 环境科学, 2007, 28(9):20682073.
[4]金一和,丁梅,翟成,等. 长江三峡库区江水和武汉地区地面水中PFOS和PFOA污染现状查[J]. 生态环境, 2006, 15(3): 486489.
[5]GIESY J P,KANNAN K. Peer reviewed: Perfluorochemical surfactants in the environment[J]. Environ Sci&Technol. 2002, 36(7): 146A152A.
[6]EHRESMAN D J,FROEHLICH J W,OLSEN G W, et al. Comparison of human whole blood, plasma,andserum matrices for the determination of perfluorooctanesulfonate (PFOS), perfluorooctanoate(PFOA), and other fluorochemicals[J]. Environ Res, 2007, 103(2): 176184.
[7]HOPF N B, RUDER A M, SUCCOP P. Background levels of polychlorinated biphenyls in the US population[J]. Sci Total Environ, 2009, 407(24): 61096119.
[8]OLSEN G W, BURRIS J M, EHRESMAN D J, et al. Halflife of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate and perfluorooctanoate in retired fluorochemical production workers [J]. Environ Health Perspect, 2007, 115(9): 1298.
[9]仇敬运,屈艾,胡文静,等. 全氟辛烷磺酸钾对小鼠肝脏的氧化性损伤研究[J]. 毒理学杂志, 2011(4):265268.
[10]范轶欧,金一和,麻懿馨,等. 全氟辛烷磺酸对雄性大鼠生精功能的影响[J]. 卫生研究, 2005, 34(1): 3739
[11]JOHANSSONN, FREDRIKSSON A, ERIKSSON P. Neonatal exposure to perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) causes neurobehavioural defects in adult mice [J].Neurotoxicology, 2008, 29(1): 160169.
[12]LIN K, HSIN H,LIBINA N, et al.Regulation of the Caenorhabditiselegans longevity protein DAF16 by insulin/IGF1 and germline signaling[J]. Nat Genet, 2001, 28(2):13945.
[13]LIBINAN, BERMAN J R, KENYON C. Tissuespecific activities of C. elegans DAF16 in the regulation of lifespan[J]. Cell, 2003,115: 489502.
[14]JOHNSON T E, TEDESCO P M, LITHGOW G J. Comparing mutants, selective breeding, and transgenics in the dissection of aging processes of Caenorhabditiselegans[J]. Genetica, 1993, 91: 6577.
[15]APFELD J, KENYON C. Cell nonautonomy of C.elegans daf2 function in the regulation of diapause and life span[J]. Cell,1998,95:199210.
[16]KANNAN K, YUN S H, RUDD R J, et al. High concentrations of persistent organic pollutants including PCBs, DDT, PBDEs and PFOS in little brown bats with whitenose syndrome in New York, USA[J]. Chemosphere, 2010, 80(6): 613618.
[17]PAIANO V, FATTORE E, CARRA A, et al. Liquid chromatographytandem mass spectrometry analysis of perfluorooctane sulfonate and perfluorooctanoic acid in fish fillet samples [J]. J Anal Methods Chem, 2012, 2012: 719010.
[18]NAOKI O, RINNA N, TOMOKA M, et al. A secreted decoy of InR antagonizes insulin/IGF signaling to restrict body growth in Drosophila [J]. Genes & Dev, 2013, 27: 8797.
[19]KENYON C J. The genetics of ageing [J]. Nature, 2010, 464(7288): 504512.
[20]SCOTT F L, MARISSA F, ANISOARA B, et al. Lifespan extension from hypoxia in Caenorhabditis elegans requires both HIF1 and DAF16 and is antagonized by SKN1[J]. J GerontolA BiolSci Med Sci, 2013, 68: 11131144.
[21]ROBERT J S R, SRINIVAS A, W ALEX C, et al. Gene categories differentially expressed in C. elegans Age〖STBX〗1〖STBZ〗 mutants of extraordinary longevity: New insights from novel datamining procedures[J]. J Gerontol A BiolSci Med Sci, 2012, 67A: 366375.