Effect of ambient polycyclic aromatic hydrocarbons and nicotine on the structure of Aβ<sub>42</sub> protein

doi:10.1007/s11783-023-1615-2

Front. Environ. Sci. Eng.

2023, Vol. 17

Issue (2) : 15 https://doi.org/10.1007/s11783-023-1615-2

RESEARCH ARTICLE

Effect of ambient polycyclic aromatic hydrocarbons and nicotine on the structure of Aβ₄₂ protein

Samal Kaumbekova¹, Mehdi Amouei Torkmahalleh¹, Naoya Sakaguchi², Masakazu Umezawa², Dhawal Shah¹(

)

¹. Department of Chemical and Materials Engineering, School of Engineering and Digital Sciences, Nazarbayev University, Kabanbay Batyr 53, Nur-Sultan, 010000, Kazakhstan
². Department of Materials Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, 6-3-1 Niijuku, Katsushika, Tokyo 125-8585, Japan

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Abstract

● B[a]P, nicotine and phenanthrene molecules altered the secondary structure of Aβ₄₂.

● β-content of the peptide was significantly enhanced in the presence of the PAHs.

● Nicotine made stable cluster with Aβ₄₂ peptide via hydrogen bonds.

● Phenanthrene due to its small size, interfered with the Aβ₄₂ monomer more strongly.

Recent studies have correlated the chronic impact of ambient environmental pollutants like polycyclic aromatic hydrocarbons (PAHs) with the progression of neurodegenerative disorders, either by using statistical data from various cities, or via tracking biomarkers during in-vivo experiments. Among different neurodegenerative disorders, PAHs are known to cause increased risk for Alzheimer’s disease, related to the development of amyloid beta (Aβ) peptide oligomers. However, the complex molecular interactions between peptide monomers and organic pollutants remains obscured. In this work, we performed an atomistic molecular dynamics study via GROMACS to investigate the structure of Aβ₄₂ peptide monomer in the presence of benzo[a]pyrene, nicotine, and phenanthrene. Interestingly the results revealed strong hydrophobic, and hydrogen-bond based interactions between Aβ peptides and these environmental pollutants that resulted in the formation of stable intermolecular clusters. The strong interactions affected the secondary structure of the Aβ₄₂ peptide in the presence of the organic pollutants, with almost 50 % decrease in the α-helix and 2 %–10 % increase in the β-sheets of the peptide. Overall, the undergoing changes in the secondary structure of the peptide monomer in the presence of the pollutants under the study indicates an enhanced formation of Aβ peptide oligomers, and consequent progression of Alzheimer’s disease.

Keywords Polycyclic aromatic hydrocarbons Nicotine toxicology Aβ₄₂ peptide Alzheimer’s disease Molecular dynamics simulations Environmental pollution

Corresponding Author(s): Dhawal Shah

About author:

Tongcan Cui and Yizhe Hou contributed equally to this work.

Issue Date: 05 September 2022

Cite this article:

Samal Kaumbekova,Mehdi Amouei Torkmahalleh,Naoya Sakaguchi, et al. Effect of ambient polycyclic aromatic hydrocarbons and nicotine on the structure of Aβ₄₂ protein[J]. Front. Environ. Sci. Eng., 2023, 17(2): 15.

URL:

https://academic.hep.com.cn/fese/EN/10.1007/s11783-023-1615-2
https://academic.hep.com.cn/fese/EN/Y2023/V17/I2/15

Tab.1 Number of molecules in the simulated systems of one Aβ₄₂ peptide and one PAH

Fig.1 (A) Formation of clusters of Aβ₄₂ monomer with B[a]P, nicotine and phenanthrene molecules, (B) change of the distances between center of masses of Aβ₄₂ monomer and B[a]P, nicotine and phenanthrene molecules within the simulation time.

Fig.2 Time-evolution of secondary structure of Aβ₄₂ monomer: (A) in the system with no pollutants, (B) in the presence of one B[a]P molecule, (C) in the presence of one nicotine molecule, (D) in the presence of phenanthrene molecule.

Tab.2 Secondary structure of Aβ₄₂ peptide monomer in the systems under the study, averaged among last 20 ns of the molecular dynamics run

Fig.3 Representative snapshots of the systems under the study (water molecules and ions are not shown) with indicated Aβ₁ of N-terminus and Aβ₄₂ of C-terminus of: (A) Aβ₄₂ monomer in the beginning of the simulations, (B) Aβ₄₂ monomer in the end of 200 ns of the simulation in the absence of environmental pollutants, (C) Aβ₄₂ monomer and B[a]P molecule in the end of molecular dynamics (MD) run, (D) Aβ₄₂ monomer and nicotine molecule in the end of MD run, (E) Aβ₄₂ monomer and phenanthrene molecule in the end of MD run. VMD coloring methods: 1. Secondary structure of peptide: beta sheet = yellow, bridge-beta = tan, alpha helix = purple, 3–10_Helix = blue, bend = cyan, turn = cyan, coil = white. 2. B[a]P molecule – grey, nicotine – blue, phenanthrene – black.

Fig.4 Distances between center of masses of the amino acid residues of Aβ₄₂ monomer and B[a]P, nicotine and phenanthrene molecules averaged within the last 20 ns of the simulations.

Fig.5 Time-evolution of (A) root-mean square deviations, (B) radius of gyration, (C) solvent accessible surface area, (D) intrapeptide H-bonds of Aβ₄₂ peptide monomer in the systems under study within the simulation time.

Fig.6 RMSF of aminoacid residues of Aβ₄₂ peptide monomer (^*: averaged among last 20 ns of the simulations that was 180–200 ns of the molecular dynamics run, ^**: in the range of 150–170 ns of the MD run).

1	M J VAbraham, D Van Der Spoel, E Lindahl, B Hess ( 2019). GROMACS User Manual Version 2019. 6
2	J F Aitken, K M Loomes, B Konarkowska, G J Cooper. (2003). Suppression by polycyclic compounds of the conversion of human amylin into insoluble amyloid. Biochemical Journal, 374( 3): 779– 784 https://doi.org/10.1042/bj20030422 pmid: 12812521
3	M Amouei Torkmahalleh, M Naseri, S Nurzhan, R Gabdrashova, Z Bekezhankyzy, A Gimnkhan, M Malekipirbazari, M Jouzizadeh, M Tabesh, H Farrokhi, et al. ( 2022). Human exposure to aerosol from indoor gas stove cooking and the resulting nervous system responses. Indoor Air, 32( 2): e12983 https://doi.org/10.1111/ina.12983 pmid: 35037300
4	W M Berhanu, U H Hansmann ( 2012). Structure and dynamics of amyloid-β segmental polymorphisms. PLoS One, 7( 7): e41479 https://doi.org/10.1371/journal.pone.0041479 pmid: 22911797
5	L Calderón-Garcidueñas ( 2016). Smoking and cerebral oxidative stress and air pollution: a dreadful equation with particulate matter involved and one more powerful reason not to smoke anything! Journal of Alzheimer’s Disease , 54( 1): 109– 112 https://doi.org/10.3233/JAD-160510 pmid: 27447427
6	S Chakraborty, P Das ( 2017). Emergence of alternative structures in amyloid beta 1-42 monomeric landscape by n-terminal hexapeptide amyloid inhibitors . Scientific Reports, 7( 1): 9941(1:12) https://doi.org/10.1038/s41598-017-10212-5 pmid: 28855598
7	G F Chen, T H Xu, Y Yan, Y R Zhou, Y Jiang, K Melcher, H E Xu. (2017). Amyloid beta: structure, biology and structure-based therapeutic development. Acta Pharmacologica Sinica, 38( 9): 1205– 1235 https://doi.org/10.1038/aps.2017.28 pmid: 28713158
8	J Cho, J Sohn, J Noh, H Jang, W Kim, S K Cho, H Seo, G Seo, S K Lee, Y Noh , et al. ( 2020). Association between exposure to polycyclic aromatic hydrocarbons and brain cortical thinning: the Environmental Pollution-Induced Neurological EFfects (EPINEF) study. Science of the Total Environment, 737: 140097 https://doi.org/10.1016/j.scitotenv.2020.140097 pmid: 32783831
9	S de Gelder, H Sundh, T N M Pelgrim, J D Rasinger, L van Daal, G Flik, M H G Berntssen, P H M Klaren. (2018). Transepithelial transfer of phenanthrene, but not of benzo[a]pyrene, is inhibited by fatty acids in the proximal intestine of rainbow trout (Oncorhynchus mykiss). Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP, 204 : 97– 105 https://doi.org/10.1016/j.cbpc.2017.11.006 pmid: 29223736
10	S C Edwards, W Jedrychowski, M Butscher, D Camann, A Kieltyka, E Mroz, E Flak, Z Li, S Wang, V Rauh, F Perera. (2010). Prenatal exposure to airborne polycyclic aromatic hydrocarbons and children’s intelligence at 5 years of age in a prospective cohort study in Poland. Environmental Health Perspectives, 118( 9): 1326– 1331 https://doi.org/10.1289/ehp.0901070 pmid: 20406721
11	D Gao, M Wu, C Wang, Y Wang, Z Zuo ( 2015). Chronic exposure to low benzo[a]pyrene level causes neurodegenerative disease-like syndromes in zebrafish ( Danio rerio ). Aquatic Toxicology (Amsterdam, Netherlands), 167: 200– 208 https://doi.org/10.1016/j.aquatox.2015.08.013 pmid: 26349946
12	S R Gerben, J A Lemkul, A M Brown, D R Bevan. (2014). Comparing atomistic molecular mechanics force fields for a difficult target: a case study on the Alzheimer’s amyloid β-peptide. Journal of Biomolecular Structure and Dynamics, 32( 11): 1817– 1832 https://doi.org/10.1080/07391102.2013.838518 pmid: 24028075
13	O Hahad, J Lelieveld, F Birklein, K Lieb, A Daiber, T Münzel ( 2020). Ambient air pollution increases the risk of cerebrovascular and neuropsychiatric disorders through induction of inflammation and oxidative stress. International Journal of Molecular Sciences, 21( 12): 4306 https://doi.org/10.3390/ijms21124306 pmid: 32560306
14	I W Hamley. (2012). The amyloid beta peptide: a chemist’s perspective. Role in Alzheimer’s and fibrillization. Chemical Reviews, 112( 10): 5147– 5192 https://doi.org/10.1021/cr3000994 pmid: 22813427
15	B Hess, H Bekker, H J C Berendsen, J G E M Fraaije. (1997). LINCS: A linear constraint solver for molecular simulations. Journal of Computational Chemistry, 18( 12): 1463– 1472 https://doi.org/10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H
16	H J Heusinkveld, T Wahle, A Campbell, R H S Westerink, L Tran, H Johnston, V Stone, F R Cassee, R P F Schins. (2016). Neurodegenerative and neurological disorders by small inhaled particles. Neurotoxicology, 56 : 94– 106 https://doi.org/10.1016/j.neuro.2016.07.007 pmid: 27448464
17	J A Holme, B C Brinchmann, M Refsnes, M Låg, J Øvrevik ( 2019). Potential role of polycyclic aromatic hydrocarbons as mediators of cardiovascular effects from combustion particles. Environmental Health, 18( 1): 74 https://doi.org/10.1186/s12940-019-0514-2 pmid: 31439044
18	W Humphrey, A Dalke, K Schulten ( 1996). VMD: visual molecular dynamics. Journal of Molecular Graphics, 14( 1): 33– 38, 27–28 https://doi.org/10.1016/0263-7855(96)00018-5 pmid: 8744570
19	P Ielpo, M R Taurino, R Buccolieri, C M Placentino, F Gallone, V Ancona, S Di Sabatino. (2018). Polycyclic aromatic hydrocarbons in a bakery indoor air: trends, dynamics, and dispersion. Environmental Science and Pollution Research International, 25( 29): 28760– 28771 https://doi.org/10.1007/s11356-018-1513-5 pmid: 29484623
20	S Jokar, M Erfani, O Bavi, S Khazaei, M Sharifzadeh, M Hajiramezanali, D Beiki, A Shamloo ( 2020). Design of peptide-based inhibitor agent against amyloid-β aggregation: molecular docking, synthesis and in vitro evaluation . Bioorganic Chemistry, 102: 104050 https://doi.org/10.1016/j.bioorg.2020.104050 pmid: 32663672
21	K P Kepp. (2012). Bioinorganic chemistry of Alzheimer’s disease. Chemical Reviews, 112( 10): 5193– 5239 https://doi.org/10.1021/cr300009x pmid: 22793492
22	N E Klepeis, W C Nelson, W R Ott, J P Robinson, A M Tsang, P Switzer, J V Behar, S C Hern, W H Engelmann. (2001). The national human activity pattern survey (NHAPS): a resource for assessing exposure to environmental pollutants. Journal of Biomolecular Structure and Dynamics, 11( 3): 231– 252 https://doi.org/10.1038/sj.jea.7500165 pmid: 11477521
23	H S Kwon, M H Ryu, C Carlsten. (2020). Ultrafine particles: unique physicochemical properties relevant to health and disease. Experimental & Molecular Medicine, 52( 3): 318– 328 https://doi.org/10.1038/s12276-020-0405-1 pmid: 32203103
24	D Liu, Y Zhao, Y Qi, Y Gao, D Tu, Y Wang, H M Gao, H Zhou ( 2020). Benzo(a)pyrene exposure induced neuronal loss, plaque deposition, and cognitive decline in APP/PS1 mice. Journal of Neuroinflammation, 17( 1): 258 https://doi.org/10.1186/s12974-020-01925-y pmid: 32867800
25	A K Malde, L Zuo, M Breeze, M Stroet, D Poger, P C Nair, C Oostenbrink, A E Mark. (2011). An Automated force field Topology Builder (ATB) and repository: version 1.0. Journal of Chemical Theory and Computation, 7( 12): 4026– 4037 https://doi.org/10.1021/ct200196m pmid: 26598349
26	E M Mandelkow, E Mandelkow ( 2012). Biochemistry and cell biology of tau protein in neurofibrillary degeneration. Cold Spring Harbor Perspectives in Medicine, 2( 7): a006247 https://doi.org/10.1101/cshperspect.a006247 pmid: 22762014
27	B Murray, B Sharma, G Belfort. (2017). N-terminal hypothesis for Alzheimer’s disease. ACS Chemical Neuroscience, 8( 3): 432– 434 https://doi.org/10.1021/acschemneuro.7b00037 pmid: 28186729
28	Z Naufal, L Zhiwen, L Zhu, G D Zhou, T McDonald, L Y He, L Mitchell, A Ren, H Zhu, R Finnell, K C Donnelly. (2010). Biomarkers of exposure to combustion by-products in a human population in Shanxi, China. Journal of Exposure Science & Environmental Epidemiology, 20( 4): 310– 319 https://doi.org/10.1038/jes.2009.19 pmid: 19277067
29	Q Niu, H Zhang, X Li, M Li. (2010). Benzo[a]pyrene-induced neurobehavioral function and neurotransmitter alterations in coke oven workers. Occupational and Environmental Medicine, 67( 7): 444– 448 https://doi.org/10.1136/oem.2009.047969 pmid: 19854696
30	G Oberdörster, Z Sharp, V Atudorei, A Elder, R Gelein, W Kreyling, C Cox. (2004). Translocation of inhaled ultrafine particles to the brain. Inhalation Toxicology, 16( 6–7): 437– 445 https://doi.org/10.1080/08958370490439597 pmid: 15204759
31	S W See, R Balasubramanian. (2008). Chemical characteristics of fine particles emitted from different gas cooking methods. Atmospheric Environment, 42( 39): 8852– 8862 https://doi.org/10.1016/j.atmosenv.2008.09.011
32	K Shang , Z Chen, Z Liu, L Song, W Zheng, B Yang, S Liu, L Yin ( 2021). Haze prediction model using deep recurrent neural network. Atmosphere (Basel), 12( 12): 1625 https://doi.org/10.3390/atmos12121625
33	C Sharma, S R Kim ( 2021). Linking oxidative stress and proteinopathy in Alzheimer’s disease. Antioxidants(Basel), 10( 8): 1231 https://doi.org/10.3390/antiox10081231 pmid: 34439479
34	B Strandberg, C Österman, H Koca Akdeva, J Moldanová, S Langer ( 2020). The use of polyurethane foam (PUF) passive air samplers in exposure studies to PAHs in Swedish seafarers. Polycyclic Aromatic Compounds, 42( 2): 448– 459
35	M Tolar, S Abushakra, M Sabbagh. (2020). The path forward in Alzheimer’s disease therapeutics: reevaluating the amyloid cascade hypothesis. Alzheimers Dement, 16( 11): 1553– 1560 https://doi.org/10.1016/j.jalz.2019.09.075 pmid: 31706733
36	S Tomaselli, V Esposito, P Vangone, N A van Nuland, A M J J Bonvin, R Guerrini, T Tancredi, P A Temussi, D Picone. (2006). The alpha-to-beta conformational transition of Alzheimer’s Abeta-(1–42) peptide in aqueous media is reversible: a step by step conformational analysis suggests the location of beta conformation seeding. Chembiochem, 7( 2): 257– 267 https://doi.org/10.1002/cbic.200500223 pmid: 16444756
37	R Verma, K S Patel, S K Verma. (2016). Indoor polycyclic aromatic hydrocarbon concentration in Central India. Polycyclic Aromatic Compounds, 36( 2): 152– 168 https://doi.org/10.1080/10406638.2014.957407
38	C Wallin, S B Sholts, N Österlund, J Luo, J Jarvet, P M Roos, L Ilag, A Gräslund, S K T S Wärmländer ( 2017). Alzheimer’s disease and cigarette smoke components: effects of nicotine, PAHs, and Cd(II), Cr(III), Pb(II), Pb(IV) ions on amyloid-β peptide aggregation. Scientific Reports, 7( 1): 14423 (1-14) https://doi.org/10.1038/s41598-017-13759-5 pmid: 29089568
39	L M Young, A E Ashcroft, S E Radford. (2017). Small molecule probes of protein aggregation. Current Opinion in Chemical Biology, 39 : 90– 99 https://doi.org/10.1016/j.cbpa.2017.06.008 pmid: 28649012
40	Z Zhang, J Tian, W Huang, L Yin, W Zheng, S Liu ( 2021). A haze prediction method based on one-dimensional convolutional neural network. Atmosphere (Basel), 12( 10): 1327 https://doi.org/10.3390/atmos12101327

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