Acetylcholinesterase as a biomarker in environmental and occupational medicine: new insights and future perspectives

Maria Giulia Lionetto, Roberto Caricato, Antonio Calisi, Maria Elena Giordano, Trifone Schettino, Maria Giulia Lionetto, Roberto Caricato, Antonio Calisi, Maria Elena Giordano, Trifone Schettino

Abstract

Acetylcholinesterase (AChE) is a key enzyme in the nervous system. It terminates nerve impulses by catalysing the hydrolysis of neurotransmitter acetylcholine. As a specific molecular target of organophosphate and carbamate pesticides, acetylcholinesterase activity and its inhibition has been early recognized to be a human biological marker of pesticide poisoning. Measurement of AChE inhibition has been increasingly used in the last two decades as a biomarker of effect on nervous system following exposure to organophosphate and carbamate pesticides in occupational and environmental medicine. The success of this biomarker arises from the fact that it meets a number of characteristics necessary for the successful application of a biological response as biomarker in human biomonitoring: the response is easy to measure, it shows a dose-dependent behavior to pollutant exposure, it is sensitive, and it exhibits a link to health adverse effects. The aim of this work is to review and discuss the recent findings about acetylcholinesterase, including its sensitivity to other pollutants and the expression of different splice variants. These insights open new perspective for the future use of this biomarker in environmental and occupational human health monitoring.

Figures

Figure 1
Figure 1
Number of papers published in the last 20 years. The research was carried out on Scopus by using two research queries, respectively: (1) “biomarker*” and “occupational medicine,” (2) “biomarker*” and “Environmental medicine” (Scopus, April 2013).
Figure 2
Figure 2
Number of papers published in the last 20 years. The research was carried out on Scopus by using two research queries, respectively: (1) “AChE” and “occupational medicine,” (2) “AChE” and “Environmental medicine” (Scopus, April 2013).
Figure 3
Figure 3
Relationship between AChE inhibition and health negative effects. Drawn on the basis of Maroni et al. [49] findings.

References

    1. Hulka BS. Overview of biological markers. In: Hulka BS, Griffith JD, Wilcosky TC, editors. Biological Markers in Epidemiology. New York, NY, USA: Oxford University Press; 1990. pp. 3–15.
    1. Naylor S. Biomarkers: current perspectives and future prospects. Expert Review of Molecular Diagnostics. 2003;3(5):525–529.
    1. Manno M, Viau C, Cocker J, et al. Biomonitoring for occupational health risk assessment (BOHRA) Toxicology Letters. 2010;192(1):3–16.
    1. Knudsen LE, Hansen ÅM. Biomarkers of intermediate endpoints in environmental and occupational health. International Journal of Hygiene and Environmental Health. 2007;210(3-4):461–470.
    1. Daniels G. Functions of red cell surface proteins. Vox Sanguinis. 2007;93(4):331–340.
    1. Costa LG, Cole TB, Vitalone A, Furlong CE. Measurement of paraoxonase (PON1) status as a potential biomarker of susceptibility to organophosphate toxicity. Clinica Chimica Acta. 2005;352(1-2):37–47.
    1. Getman DK, Eubanks JH, Camp S, Evans GA, Taylor P. The human gene encoding acetylcholinesterase is located on the long arm of chromosome 7. American Journal of Human Genetics. 1992;51(1):170–177.
    1. Massoulié J. The origin of the molecular diversity and functional anchoring of cholinesterases. NeuroSignals. 2002;11(3):130–143.
    1. Meshorer E, Soreq H. Virtues and woes of AChE alternative splicing in stress-related neuropathologies. Trends in Neurosciences. 2006;29(4):216–224.
    1. Park SE, Kim ND, Yoo YH. Acetylcholinesterase plays a pivotal role in apoptosome formation. Cancer Research. 2004;64(24):2652–2655.
    1. Grisaru D, Sternfeld M, Eldor A, Glick D, Soreq H. Structural roles of acetylcholinesterase variants in biology and pathology. European Journal of Biochemistry. 1999;264(3):672–686.
    1. Pick M, Flores-Flores C, Grisaru D, Shochat S, Deutsch V, Soreq H. Blood-cell-specific acetylcholinesterase splice variations under changing stimuli. International Journal of Developmental Neuroscience. 2004;22(7):523–531.
    1. Taylor P, Radić Z. The cholinesterases: from genes to proteins. Annual Review of Pharmacology and Toxicology. 1994;34:281–320.
    1. Hobbiger F. The inhibition of acetylcholinesterase by organophosphorus compounds and its reversal. Proceedings of the Royal Society of Medicine. 1961;54:403–405.
    1. Sultatos LG, Kaushik R. Interactions of chlorpyrifos oxon and acetylcholinesterase. FASEB Journal. 2007;21:883–892.
    1. Barr DB, Allen R, Olsson AO, et al. Concentrations of selective metabolites of organophosphorus pesticides in the United States population. Environmental Research. 2005;99(3):314–326.
    1. Lionetto MG, Caricato R, Giordano ME, Pascariello MF, Marinosci L, Schettino T. Integrated use of biomarkers (acetylcholinesterase and antioxidant enzymes activities) in Mytilus galloprovincialis and Mullus barbatus in an Italian coastal marine area. Marine Pollution Bulletin. 2003;46(3):324–330.
    1. Lionetto MG, Caricato R, Giordano ME, Schettino T. Biomarker application for the study of chemical contamination risk on marine organisms in the Taranto marine coastal area. Chemistry and Ecology. 2004;20(1):S333–S343.
    1. Calisi A, Lionetto MG, Schettino T. Pollutant-induced alterations of granulocyte morphology in the earthworm Eisenia foetida . Ecotoxicology and Environmental Safety. 2009;72(5):1369–1377.
    1. Calisi A, Lionetto MG, Schettino T. Biomarker response in the earthworm Lumbricus terrestris exposed to chemical pollutants. Science of the Total Environment. 2011;409(20):4456–4464.
    1. Zhang LP, Hong HS, Chen ZT, Chen WQ, Calamari D. An initial environmental risk assessment of pesticide application in Xiamen seas. Jiournal of Xiamen University. 1999;38:96–102.
    1. Dogheim SM, Mohamed EL-Z, Gad Alla SA, et al. Monitoring of pesticide residues in human milk, soil, water, and food samples collected from Kafr El-Zayat governorate. Journal of AOAC International. 1996;79(1):111–116.
    1. Garrido T, Fraile J, Ninerola JM, Figueras M, Ginebreda A, Olivella L. Survey of ground water pesticide pollution in rural areas of Catalonia (Spain) International Journal of Environmental Analytical Chemistry. 2000;78(1):51–65.
    1. Hernández F, Serrano R, Miralles MC, Font N. Gas and liquid chromatography and enzyme linked immuno sorbent assay in pesticide monitoring of surface water from the western mediterranean (Comunidad Valenciana, Spain) Chromatographia. 1996;42(3-4):151–158.
    1. Barceló D, Porte C, Cid J. Determination of organophophorus compounds in Mediterranean coastal waters and biota samples using gas-chromatography with nitrogen-phosphorus and chemical ionization mass spectrometric detection. International Journal of Environmental Anaytical Chemistry. 1990;38:199–209.
    1. Pehkonen SO, Zhang Q. The degradation of organophosphorus pesticides in natural waters: a critical review. Critical Reviews in Environmental Science and Technology. 2002;32(1):17–72.
    1. Black RM, Read RW. Biological markers of exposure to organophosphorus nerve agent. Archives of Toxicology. 2013;87:421–437.
    1. Black RM. An overview of biological markers of exposure to chemical warfare agents. Journal of Analytical Toxicology. 2008;32(1):1–8.
    1. Ng V, Koh D, Wee A, Chia S-E. Salivary acetylcholinesterase as a biomarker for organophosphate exposure. Occupational Medicine. 2009;59(2):120–122.
    1. Hernández AF, López O, Rodrigo L, et al. Changes in erythrocyte enzymes in humans long-term exposed to pesticides: influence of several markers of individual susceptibility. Toxicology Letters. 2005;159(1):13–21.
    1. Souza MS, Magnarelli GG, Rovedatti MG, Santa Cruz S, De D’Angelo AMP. Prenatal exposure to pesticides: analysis of human placental acetylcholinesterase, glutathione S-transferase and catalase as biomarkers of effect. Biomarkers. 2005;10(5):376–389.
    1. Safi JM, Abu Mourad TA, Yassin MM. Hematological biomarkers in farm workers exposed to organophosphorus pesticides in the Gaza Strip. Archives of Environmental and Occupational Health. 2005;60(5):235–241.
    1. Simoniello MF, Kleinsorge EC, Scagnetti JA, et al. Biomarkers of cellular reaction to pesticide exposure in a rural population. Biomarkers. 2010;15(1):52–60.
    1. Araoud M, Neffeti F, Douki W, et al. Factors influencing plasma butyrylcholinesterase activity in agricultural workers. Annales de Biologie Clinique. 2011;69(2):159–166.
    1. He F. Biological monitoring of exposure to pesticides: current issues. Toxicology Letters. 1999;108(2-3):277–283.
    1. Kamel F, Hoppin JA. Association of pesticide exposure with neurologic dysfunction and disease. Environmental Health Perspectives. 2004;112(9):950–958.
    1. Ellman GL, Courtney KD, Andres V, Jr., Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology. 1961;7(2):88–95.
    1. Henn BC, McMaster S, Padilla S. Measuring cholinesterase activity in human saliva. Journal of Toxicology and Environmental Health A. 2006;69(19):1805–1818.
    1. Koh DS-Q, Koh GC-H. The use of salivary biomarkers in occupational and environmental medicine. Occupational and Environmental Medicine. 2007;64(3):202–210.
    1. Ueda K, Yamaguchi K. Cholinesterase activity of human saliva and types of the enzymes. Comparison of whole saliva with parotid saliva. The Bulletin of Tokyo Dental College. 1976;17(4):231–241.
    1. Sayer R, Law E, Connelly PJ, Breen KC. Association of a salivary acetylcholinesterase with Alzheimer’s disease and response to cholinesterase inhibitors. Clinical Biochemistry. 2004;37(2):98–104.
    1. Abdollahi M, Balali-Mood M, Akhgari M, Jannat B, Kebriaeezadeh A, Nikfar S. A survey of cholinesterase activity in healthy and organophosphate exposed populations. Iranian Journal of Medical Sciences. 1996;21:p. 68.
    1. Henn BC, McMaster S, Padilla S. Measuring cholinesterase activity in human saliva. Journal of Toxicology and Environmental Health A. 2006;69(19):1805–1818.
    1. Ng V, Koh D, Wee A, Chia S-E. Salivary acetylcholinesterase as a biomarker for organophosphate exposure. Occupational Medicine. 2009;59(2):120–122.
    1. Nigg HN, Knaak JB. Blood cholinesterases as human biomarkers of organophosphorus pesticide exposure. Reviews of Environmental Contamination and Toxicology. 2000;163:29–111.
    1. Hernández AF, Gómez MA, Pena G, et al. Effect of long-term exposure to pesticides on plasma esterases from plastic greenhouse workers. Journal of Toxicology and Environmental Health A. 2004;67(14):1095–1108.
    1. Remor AP, Totti CC, Moreira DA, Dutra GP, Heuser VD, Boeira JM. Occupational exposure of farm workers to pesticides: biochemical parameters and evaluation of genotoxicity. Environment International. 2009;35(2):273–278.
    1. Mourad TA. Adverse impact of insecticides on the health of Palestinian farm workers in the Gaza Strip: a hematologic biomarker study. International Journal of Occupational and Environmental Health. 2005;11(2):144–149.
    1. Maroni M, Colosio C, Ferioli A, Fait A. Biological Monitoring of Pesticide Exposure: a review. Introduction. Toxicology. 2000;143(1):5–118.
    1. Bressler JP, Goldstein GW. Mechanisms of lead neurotoxicity. Biochemical Pharmacology. 1991;41(4):479–484.
    1. Goldstein GW. Neurologic concepts of lead poisoning in children. Pediatric Annals. 1992;21(6):384–388.
    1. Lionetto MG, Caricato R, Giordano ME, Schettino T. Biomarker application for the study of chemical contamination risk on marine organisms in the Taranto marine coastal area. Chemistry and Ecology. 2004;20(1):S333–S343.
    1. Jebali J, Banni M, Guerbej H, Almeida EA, Bannaoui A, Boussetta H. Effects of malathion and cadmium on acetylcholinesterase activity and metallothionein levels in the fish Seriola dumerilli . Fish Physiology and Biochemistry. 2006;32(1):93–98.
    1. Vioque-Fernández A, de Almeida EA, Ballesteros J, García-Barrera T, Gómez-Ariza J-L, López-Barea J. Doñana National Park survey using crayfish (Procambarus clarkii) as bioindicator: esterase inhibition and pollutant levels. Toxicology Letters. 2007;168(3):260–268.
    1. Costa LG. Effects of neurotoxicants on brain neurochemistry. In: Tilson H, Mitchell, editors. Neurotoxicology. New York, NY, USA: Raven Press; 1992. pp. 101–124.
    1. Frasco MF, Fournier D, Carvalho F, Guilhermino L. Do metals inhibit acetylcholinesterase (AchE)? Implementation of assay conditions for the use of AchE activity as a biomarker of metal toxicity. Biomarkers. 2005;10(5):360–375.
    1. Ademuyiwa O, Ugbaja RN, Rotimi SO, et al. Erythrocyte acetylcholinesterase activity as a surrogate indicator of lead-induced neurotoxicity in occupational lead exposure in Abeokuta, Nigeria. Environmental Toxicology and Pharmacology. 2007;24(2):183–188.
    1. Reddy PM, Philip GH. In vivo inhibition of AChE and ATPase activities in the tissues of freshwater fish, Cyprinus carpio exposed to technical grade cypermethrin. Bulletin of Environmental Contamination and Toxicology. 1994;52(4):619–626.
    1. Davies PE, Cook LSJ. Catastrophic macroinvertebrate drift and sublethal effects on brown trout, Salmo trutta, caused by cypermethrin spraying on a Tasmanian stream. Aquatic Toxicology. 1993;27(3-4):201–224.
    1. Szabo A, Nemcsok J, Asztalos B, Rakonczay Z, Kasa P, Le Huu Hieu LHH. The effect of pesticides on carp (Cyprinus carpio L). Acetylcholinesterase and its biochemical characterization. Ecotoxicology and Environmental Safety. 1992;23(1):39–45.
    1. Hernández AF, López O, Rodrigo L, et al. Changes in erythrocyte enzymes in humans long-term exposed to pesticides: influence of several markers of individual susceptibility. Toxicology Letters. 2005;159(1):13–21.
    1. Kang J-J, Fang H-W. Polycyclic aromatic hydrocarbons inhibit the activity of acetylcholinesterase purified from electric eel. Biochemical and Biophysical Research Communications. 1997;238(2):367–369.
    1. Jett DA, Navoa RV, Lyons MA., Jr. Additive inhibitory action of chlorpyrifos and polycyclic aromatic hydrocarbons on acetylcholinesterase activity in vitro. Toxicology Letters. 1999;105(3):223–229.
    1. Buzea C, Pacheco I, Robbie K. Nanomaterials and nanoparticles: sources and toxicity. Biointerphases. 2007;2(2):MR17–MR71.
    1. Indennidate L, Cannoletta D, Lionetto F, Greco A, Maffezzoli A. Nanofilled polyols for viscoelastic polyurethane foams. Polymer International. 2010;59(4):486–491.
    1. Wang Z, Zhao J, Li F, Gao D, Xing B. Adsorption and inhibition of acetylcholinesterase by different nanoparticles. Chemosphere. 2009;77(1):67–73.
    1. Bigbee JW, Sharma KV, Chan EL-P, Bögler O. Evidence for the direct role of acetylcholinesterase in neurite outgrowth in primary dorsal root ganglion neurons. Brain Research. 2000;861(2):354–362.
    1. Sternfeld M, Ming G-L, Song H-J, et al. Acetylcholinesterase enhances neurite growth and synapse development through alternative contributions of its hydrolytic capacity, core protein, and variable C termini. Journal of Neuroscience. 1998;18(4):1240–1249.
    1. Bigbee JW, Sharma KV. The adhesive role of acetylcholinesterase (AChE): detection of AChE binding proteins in developing rat spinal cord. Neurochemical Research. 2004;29(11):2043–2050.
    1. Byers DM, Irwin LN, Moss DE, Sumaya IC, Hohmann CF. Prenatal exposure to the acetylcholinesterase inhibitor methanesulfonyl fluoride alters forebrain morphology and gene expression. Developmental Brain Research. 2005;158(1-2):13–22.
    1. Grisaru D, Pick M, Perry C, et al. Hydrolytic and nonenzymatic functions of acetylcholinesterase comodulate hemopoietic stress responses. Journal of Immunology. 2006;176(1):27–35.
    1. Soreq H, Seidman S. Acetylcholinesterase—new roles for an old actor. Nature Reviews Neuroscience. 2001;2(4):294–302.
    1. Kaufer D, Friedman A, Seidman S, Soreq H. Acute stress facilitates long-lasting changes in cholinergic gene expression. Nature. 1998;393(6683):373–377.
    1. Meshorer E, Bryk B, Toiber D, et al. SC35 promotes sustainable stress-induced alternative splicing of neuronal acetylcholinesterase mRNA. Molecular Psychiatry. 2005;10(11):985–997.
    1. Jameson RR, Seidler FJ, Slotkin TA. Nonenzymatic functions of acetylcholinesterase splice variants in the developmental neurotoxicity of organophosphates: chlorpyrifos, chlorpyrifos oxon, and diazinon. Environmental Health Perspectives. 2007;115(1):65–70.
    1. Slotkin TA. Developmental neurotoxicity of organophosphates: a case study of chlorpyrifos. In: Gupta RC, editor. Toxicity of Organophosphate and Carbamate Pesticides. San Diego, Calif, USA: Elsevier Academic Press; 2005. pp. 293–314.
    1. Slotkin TA, Levin ED, Seidler FJ. Comparative developmental neurotoxicity of organophosphate insecticides: effects on brain development are separable from systemic toxicity. Environmental Health Perspectives. 2006;114(5):746–751.
    1. Slotkin TA, Tate CA, Ryde IT, Levin ED, Seidler FJ. Organophosphate insecticides target the serotonergic system in developing rat brain regions: disparate effects of diazinon and parathion at doses spanning the threshold for cholinesterase inhibition. Environmental Health Perspectives. 2006;114(10):1542–1546.
    1. Rauh VA, Garfinkel R, Perera FP, et al. Impact of prenatal chlorpyrifos exposure on neurodevelopment in the first 3 years of life among inner-city children. Pediatrics. 2006;118(6):e1845–e1859.
    1. Damodaran TV, Jones KH, Patel AG, Abou-Donia MB. Sarin (nerve agent GB)-induced differential expression of mRNA coding for the acetylcholinesterase gene in the rat central nervous system. Biochemical Pharmacology. 2003;65(12):2041–2047.
    1. Salmon A, Erb C, Meshorer E, et al. Muscarinic modulations of neuronal anticholinesterase responses. Chemico-Biological Interactions. 2005;157-158:105–113.
    1. Yang D, Howard A, Bruun D, Ajua-Alemanj M, Pickart C, Lein PJ. Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the morphogenic activity of acetylcholinesterase. Toxicology and Applied Pharmacology. 2008;228(1):32–41.
    1. Hayden KM, Norton MC, Darcey D, et al. Occupational exposure to pesticides increases the risk of incident AD: the Cache County Study. Neurology. 2010;74(19):1524–1530.
    1. Bouchard MF, Bellinger DC, Wright RO, Weisskopf MG. Attention-deficit/hyperactivity disorder and urinary metabolites of organophosphate pesticides. Pediatrics. 2010;125(6):e1270–e1277.
    1. Darreh-Shori T, Hellström-Lindahl E, Flores-Flores C, Guan ZZ, Soreq H, Nordberg A. Long-lasting acetylcholinesterase splice variations in anticholinesterase-treated Alzheimer’s disease patients. Journal of Neurochemistry. 2004;88(5):1102–1113.

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