Abstract
Fine particulate matter (PM2.5) is an important risk factor affecting human health. Therefore, a quick method for finding metabolic targets in situ in ambient fine particulate matter is crucial. In this study, the impact of PM2.5 on human lung epithelial cells (A549) was investigated by Raman spectroscopy and mass spectrometry (MS)–based nontargeted metabolomics analysis. Raman detection indicated that exposure to PM2.5 reduced the levels of phenylalanine, tyrosine, and nucleotides. Metabolomics results not only demonstrated a significant decrease of the aforementioned metabolites but also added some important metabolite information that could not be detected by Raman spectroscopy. Our study demonstrated that Raman spectroscopy was an in situ, real-time, and rapid detection method for detecting metabolites, especially suitable for the assignment of phenylalanine/tyrosine and nucleotides, which play important roles in cellular growth. Moreover, the metabolic profiling changes observed upon PM2.5 treatment mainly involved phenylalanine, tyrosine metabolism, purine and pyrimidine metabolism, and energy metabolism, clearly demonstrating that PM2.5 can inhibit the synthesis of protein and DNA/RNA and reduce cellular energy supplies, further influencing cellular proliferation and other activities.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
The data that support the findings of this study will be available from the corresponding author upon a reasonable request.
References
Ali MRK, Wu Y, Han T, Zang X, Xiao H, Tang Y, Wu R, Fernández FM, El-Sayed MA (2016) Simultaneous time-dependent surface-enhanced Raman spectroscopy, metabolomics, and proteomics reveal cancer cell death mechanisms associated with gold nanorod photothermal therapy. J Am Chem Soc 138:15434–15442. https://doi.org/10.1021/jacs.6b08787
Beinert AJ, Büchler A, Romer P, Haueisen V, Rendler LC, Schubert MC, Heinrich M, Aktaa J, Eitner U (2019) Enabling the measurement of thermomechanical stress in solar cells and PV modules by confocal micro-Raman spectroscopy. Sol Energ Mat Sol C 193:351–360. https://doi.org/10.1016/j.solmat.2019.01.028
Bo Y, Jin C, Liu Y, Yu W, Kang H (2014) Metabolomic analysis on the toxicological effects of TiO2 nanoparticles in mouse fibroblast cells: from the perspective of perturbations in amino acid metabolism. Toxicol Mech Method 24:461–469. https://doi.org/10.3109/15376516.2014.939321
Burnstock G (2018) Purine and purinergic receptors. Brain and Neuroscience Advances 2:1101992299. https://doi.org/10.1177/2398212818817494
Chaleckis R, Meister I, Zhang P, Wheelock CE (2019) Challenges, progress and promises of metabolite annotation for LC-MS-based metabolomics. Curr Opin Biotech 55:44–50. https://doi.org/10.1016/j.copbio.2018.07.010
Deng X, Zhang F, Rui W, Long F, Wang L, Feng Z, Chen D, Ding W (2013) PM2.5-induced oxidative stress triggers autophagy in human lung epithelial A549 cells. Toxicol in Vitro 27:1762–1770. https://doi.org/10.1016/j.tiv.2013.05.004
Emwas A, Roy R, Mckay RT, Tenori L, Saccenti E, Gowda GAN, Raftery D, Alahmari F, Jaremko L, Jaremko M, Wishart DS (2019) NMR Spectroscopy for Metabolomics Research. Metabolites 9:123. https://doi.org/10.3390/metabo9070123
Fan J, Li S, Fan C, Bai Z, Yang K (2016) The impact of PM2.5 on asthma emergency department visits: a systematic review and meta-analysis. Environ Sci Pollut R 23:843–850. https://doi.org/10.1007/s11356-015-5321-x
Fazio E, Speciale A, Spadaro S, Bonsignore M, Cimino F, Cristani M, Trombetta D, Saija A, Neri F (2018) Evaluation of biological response induced by molybdenum oxide nanocolloids on in vitro cultured NIH/3T3 fibroblast cells by micro-Raman spectroscopy. Colloids Surf, B 170:233–241. https://doi.org/10.1016/j.colsurfb.2018.06.028
Gostner J M, Becker K, Kurz K,Fuchs D (2015) Disturbed amino acid metabolism in HIV: association with neuropsychiatric symptoms. Front Psychiatry 6 https://doi.org/10.3389/fpsyt.2015.00097
Griffin JWD, Bradshaw PC (2017) Amino acid catabolism in Alzheimer’s disease brain: friend or foe? Oxid Med Cell Longev 2017:1–15. https://doi.org/10.1155/2017/5472792
Gu X, Chu X, Zeng X, Bao H, Liu X (2017) Effects of PM2.5 exposure on the notch signaling pathway and immune imbalance in chronic obstructive pulmonary disease. Environ Pollut 226:163–173. https://doi.org/10.1016/j.envpol.2017.03.070
Huang D, Zou Y, Abbas A, Dai B (2018) Nuclear magnetic resonance-based metabolomic investigation reveals metabolic perturbations in PM2.5-treated A549 cells. Environ Sci Pollut R 25:31656–31665. https://doi.org/10.1007/s11356-018-3111-y
Jin C, Liu Y, Sun L, Chen T, Zhang Y, Zhao A, Wang X, Cristau M, Wang K, Jia W (2013) Metabolic profiling reveals disorder of carbohydrate metabolism in mouse fibroblast cells induced by titanium dioxide nanoparticles. J Appl Toxicol 33:1442–1450. https://doi.org/10.1002/jat.2808
Kang B, Austin LA, El-Sayed MA (2014) Observing real-time molecular event dynamics of apoptosis in living cancer cells using nuclear-targeted plasmonically enhanced Raman nanoprobes. ACS Nano 8:4883–4892. https://doi.org/10.1021/nn500840x
Kelly B, Pearce EL (2020) Amino assets: how amino acids support immunity. Cell Metab 32:154–175. https://doi.org/10.1016/j.cmet.2020.06.010
Leclercq B, Platel A, Antherieu S, Alleman LY, Hardy EM, Perdrix E, Grova N, Riffault V, Appenzeller BM, Happillon M, Nesslany F, Coddeville P, Lo-Guidice J, Garçon G (2017) Genetic and epigenetic alterations in normal and sensitive COPD-diseased human bronchial epithelial cells repeatedly exposed to air pollution-derived PM2.5. Environ Pollut 230:163–177. https://doi.org/10.1016/j.envpol.2017.06.028
Li D, Li Y, Li G, Zhang Y, Li J, Chen H (2019) Fluorescent reconstitution on deposition of PM2.5 in lung and extrapulmonary organs. Proc Natl Acad Sci 116:2488–2493. https://doi.org/10.1073/pnas.1818134116
Li J, Hu Y, Liu L, Wang Q, Zeng J, Chen C (2020) PM2.5 exposure perturbs lung microbiome and its metabolic profile in mice. Sci Total Environ 721:137432. https://doi.org/10.1016/j.scitotenv.2020.137432
Luan H, Wang X, Cai Z (2017) Mass spectrometry-based metabolomics: targeting the crosstalk between gut microbiota and brain in neurodegenerative disorders. Mass Spectrom Rev 38:22–33. https://doi.org/10.1002/mas.21553
Maiti NC, Apetri MM, Zagorski MG, Carey PR, Anderson VE (2004) Raman spectroscopic characterization of secondary structure in natively unfolded proteins: α-Synuclein. J Am Chem Soc 126:2399–2408. https://doi.org/10.1021/ja0356176
Mehta M, Chen L, Gordon T, Rom W, Tang M (2008) Particulate matter inhibits DNA repair and enhances mutagenesis. Mutat Res Genet Toxicol Environ Mutagen 657:116–121. https://doi.org/10.1016/j.mrgentox.2008.08.015
Movasaghi Z, Rehman S, Rehman IU (2007) Raman spectroscopy of biological tissues. Appl Spectrosc Rev 42:5, 493–541. https://doi.org/10.1080/05704920701551530
Nagatsu T, Nagatsu I (2016) Tyrosine hydroxylase (TH), its cofactor tetrahydrobiopterin (BH4), other catecholamine-related enzymes, and their human genes in relation to the drug and gene therapies of Parkinson’s disease (PD): historical overview and future prospects. J Neural Transm 123:1255–1278. https://doi.org/10.1007/s00702-016-1596-4
Polichetti G, Cocco S, Spinali A, Trimarco V, Nunziata A (2009) Effects of particulate matter (PM10, PM2.5 and PM1) on the cardiovascular system. Toxicology 261:1–8. https://doi.org/10.1016/j.tox.2009.04.035
Polosa R (2002) Adenosine-receptor subtypes: their relevance to adenosine-mediated responses in asthma and chronic obstructive pulmonary disease. Eur Respir J 20:488–496. https://doi.org/10.1183/09031936.02.01132002
Pun VC, Kazemiparkouhi F, Manjourides J, Suh HH (2017) Long-Term PM2.5 exposure and respiratory, cancer, and cardiovascular mortality in older US adults. Am J Epidemiol 186:961–969. https://doi.org/10.1093/aje/kwx166
Rajagopalan S, Al-Kindi SG, Brook RD (2018) Air pollution and cardiovascular disease. J Am Coll Cardiol 72:2054–2070. https://doi.org/10.1016/j.jacc.2018.07.099
Riva DR, Magalhaes CB, Lopes AA, Lancas T, Mauad T, Malm O, Valenca SS, Saldiva PH, Faffe DS, Zin WA (2011) Low dose of fine particulate matter (PM2.5) can induce acute oxidative stress, inflammation and pulmonary impairment in healthy mice. Inhal Toxicol 23:257–267. https://doi.org/10.3109/08958378.2011.566290
Song Y, Li R, Zhang Y, Wei J, Chen W, Chung CKA, Cai Z (2019) Mass spectrometry-based metabolomics reveals the mechanism of ambient fine particulate matter and its components on energy metabolic reprogramming in BEAS-2B cells. Sci Total Environ 651:3139–3150. https://doi.org/10.1016/j.scitotenv.2018.10.171
Van Winkle LS, Bein K, Anderson D, Pinkerton KE, Tablin F, Wilson D, Wexler AS (2015) Biological dose response to PM2.5: effect of particle extraction method on platelet and lung responses. Toxicol Sci 143:349–359. https://doi.org/10.1093/toxsci/kfu230
Vanhove K, Derveaux E, Graulus G, Mesotten L, Thomeer M, Noben J, Guedens W, Adriaensens P (2019) Glutamine addiction and therapeutic strategies in lung cancer. Int J Mol Sci 20:252. https://doi.org/10.3390/ijms20020252
Wang D, He P, Wang Z, Li G, Majed N, Gu AZ (2020) Advances in single cell Raman spectroscopy technologies for biological and environmental applications. Curr Opin Biotech 64:218–229. https://doi.org/10.1016/j.copbio.2020.06.011
Wang Z, Gao S, Xie J, Li R (2019) Identification of multiple dysregulated metabolic pathways by GC-MS-based profiling of lung tissue in mice with PM2.5-induced asthma. Chemosphere 220:1–10. https://doi.org/10.1016/j.chemosphere.2018.12.092
Warwick B, Dunn DIE (2005) Metabolomics: Current analytical platforms and methodologies. Trends Anal Chem 24:285–294. https://doi.org/10.1016/j.trac.2004.11.021
Wu G (2009) Amino acids: metabolism, functions, and nutrition. Amino Acids 37:1–17. https://doi.org/10.1007/s00726-009-0269-0
Xu L, Yang J, Xue B, Zhang C, Shi L, Wu C, Su Y, Jin X, Liu Y, Zhu X (2017) Molecular insights for the biological interactions between polyethylene glycol and cells. Biomaterials 147:1–13. https://doi.org/10.1016/j.biomaterials.2017.09.002
Xu N, Zhu P, Liang J, Liu L, Zhang W, Li X, He Y (2019a) Label-free Raman spectroscopy monitoring of cytotoxic response induced by a telomerase inhibitor. Sens Actuators, B Chem 293:1–10. https://doi.org/10.1016/j.snb.2019.03.146
Xu Z, Li Z, Liao Z, Gao S, Hua L, Ye X, Wang Y, Jiang S, Wang N, Zhou D, Deng X (2019b) PM2.5 induced pulmonary fibrosis in vivo and in vitro. Ecotox Environ Safe 171:112–121. https://doi.org/10.1016/j.ecoenv.2018.12.061
Zhang J, Liu J, Ren L, Wei J, Duan J, Zhang L, Zhou X, Sun Z (2018) PM2.5 induces male reproductive toxicity via mitochondrial dysfunction, DNA damage and RIPK1 mediated apoptotic signaling pathway. Sci Total Environ 634:1435–1444. https://doi.org/10.1016/j.scitotenv.2018.03.383
Zhao Z, Lv S, Zhang Y, Zhao Q, Shen L, Xu S, Yu J, Hou J, Jin C (2019) Characteristics and source apportionment of PM2.5 in Jiaxing. China Environ Sci Pollut R 26:7497–7511. https://doi.org/10.1007/s11356-019-04205-2
Zou Y, Jin C, Su Y, Li J, Zhu B (2016) Water soluble and insoluble components of urban PM2.5 and their cytotoxic effects on epithelial cells (A549) in vitro. Environ Pollut 212:627–635. https://doi.org/10.1016/j.envpol.2016.03.022
Funding
This study was funded by Shanghai Natural Science Foundation of the Science and Technology Commission of Shanghai Municipal Government (No. 18ZR1418300) and the Medical-Engineering Crossover Fund (No. YG2017QN65, No. ZH2018QNA10, and No. YG2019QNA21) of Shanghai Jiao Tong University.
Author information
Authors and Affiliations
Contributions
D.L. designed the research, performed the experiments, analyzed the results, and wrote the manuscript. Y.L. and L.F. supervised and assisted in the metabolomics analysis. L.X. supervised the cell metabolomic experiments. R.W. supervised the Raman experiments. C.J. conceived the research, supervised the research design, results interpretation, and manuscript preparation. All authors discussed the results and approved the manuscript.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
The authors are giving ethical approval and consent for the said paper.
Consent for publication
The authors are giving their consent for the said paper to be published in ESPR.
Competing interests
The authors declare no competing interests.
Additional information
Responsible Editor: Gerald Thouand
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Highlights
• Raman spectroscopy is an in situ, real-time, and rapid detection method for metabolites that is especially suitable for the assignment of phenylalanine/tyrosine and nucleotides.
• MS-based metabolomics can verify and complement Raman spectroscopy, and the integration of these two methods comprehensively reveals metabolic profiling disturbances caused by PM2.5.
• PM2.5 mainly interferes with phenylalanine, tyrosine metabolism, purine and pyrimidine metabolism, and energy metabolism in A549 cells.
Supplementary Information
Below is the link to the electronic supplementary material.
Supplementary file1
(DOCX 139 KB)
Rights and permissions
About this article
Cite this article
Liu, D., Liu, Y., Wang, R. et al. Metabolic profiling disturbance of PM2.5 revealed by Raman spectroscopy and mass spectrometry–based nontargeted metabolomics. Environ Sci Pollut Res 29, 74500–74511 (2022). https://doi.org/10.1007/s11356-022-20506-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11356-022-20506-5