MitoQ Alleviated PM2.5 Induced Pulmonary Epithelial Cells Injury by Inhibiting Mitochondrial-Mediated Apoptosis
Abstract
Background: Fine particulate matter (PM2.5), an important component of ambient air pollution, induces significant adverse health effects. MitoQuinone (MitoQ), a mitochondria-targeted antioxidant, has been reported to play a protective role in various diseases. However, the roles of MitoQ in PM2.5 induced pulmonary toxicity remains to be elucidated.
Methods: All the experiments were performed at Higher Educational Key Laboratory for Translational Oncology of Fujian Province, Putian City, China in 2023. Pulmonary epithelial cells (A549) were pretreated with 4 µM MitoQ for 2 h and exposed to PM2.5 for 24 h. Cell viability was tested through CCK8 assay. Oxidative stress state and active mitochondria was used to study MitoQ’s effect on PM2.5 induced injury, and cell apoptosis was measured using a flow cytometer and analyzed by Bcl-2 family.
Results: MitoQ pretreatment significantly relieved a decreased cell viability, subsequently, MitoQ alleviated ROS production and prevented the reduction of T-AOC and GSH and increased the expression of NF-E2-related factor 2 (Nrf2) and p62 in A549 cells exposed to PM2.5. MitoQ restored the decreased mitochondrial dysfunction and dynamics disorder and inhibited activated mitochondrial-mediated apoptosis induced by PM2.5. Furthermore, the decreased ratio of Bcl-2/Bax and expression of Mcl-1 and the enhanced expression of Caspase-3 were reversed by MitoQ pretreatment.
Conclusion: MitoQ might be regarded as a potential drug to relieve PM2.5 induced pulmonary epithelial cells damage.
1. Wang C, Xu J, Yang L, et al (2018). Preva-lence and risk factors of chronic ob-structive pulmonary disease in China (the China Pulmonary Health [CPH] study): A national cross-sectional study. Lancet, 391(10131): 1706-1717.
2. Hu G, Zhong N, Ran P (2015). Air pollution and COPD in China. J Thorac Dis, 7(1):59-66.
3. Kaur M, Chandel J, Malik J, et al (2022). Particulate matter in COPD pathogene-sis: An overview. Inflamm Res, 71(7-8):797-815.
4. Leclercq B, Kluza J, Antherieu S, et al (2018). Air pollution-derived PM2.5 im-pairs mitochondrial function in healthy and chronic obstructive pulmonary dis-eased human bronchial epithelial cells. Environ Pollut, 243(Pt B):1434-49.
5. Song C, He J, Wu L, et al (2017). Health burden attributable to ambient PM2.5 in China. Environ Pollut, 223:575-86.
6. Xing YF, Xu YH, Shi MH, et al (2016). The impact of PM2.5 on the human respira-tory system. J Thorac Dis, 8(1):E69-74.
7. Wang Y, Zhong Y, Liao J, et al (2021). PM2.5-related cell death patterns. Int J Med Sci, 18(4):1024-9.
8. Deng X, Zhang F, Rui W, et al (2013). PM2.5-induced oxidative stress triggers autophagy in human lung epithelial A549 cells. Toxicol In Vitro, 27(6):1762-70.
9. Leclercq B, Kluza J, Anthérieu S, et al (2018). Mitochondrion: A critical target for the toxicity of air pollution-derived PM2.5 in healthy and COPD human bronchial epithelial cells. Eur Respir J, 52(suppl 62):PA1201.
10. Liu X, Zhao X, Li X, et al (2020). PM2.5 triggered apoptosis in lung epithelial cells through the mitochondrial apop-totic way mediated by a ROS-DRP1-mitochondrial fission axis. J Hazard Ma-ter, 397:122608.
11. Zinovkin RA, Zamyatnin AA (2019). Mito-chondria-Targeted Drugs. Curr Mol Pharmacol, 12(3):202-14.
12. Smith RAJ, Murphy MP (2010). Animal and human studies with the mitochondria-targeted antioxidant MitoQ. Ann N Y Acad Sci, 1201:96-103.
13. Cui L, Zhou Q, Zheng X, et al (2020). Mi-toQuinone attenuates vascular calcifica-tion by suppressing oxidative stress and reducing apoptosis of vascular smooth muscle cells via the Keap1/Nrf2 path-way. Free Radic Biol Med, 161:23-31.
14. Liu C, Sun Z, Wang M, et al (2022). Mi-toQuinone mitigates paraquat-induced A549 lung epithelial cell injury by pro-moting MFN1/MFN2-mediated mito-chondrial fusion. J Biochem Mol Toxicol, 36(9):e23127.
15. Lin Q, Zhang CF, Guo JL, et al (2022). In-volvement of NEAT1/PINK1-mediated mitophagy in chronic obstructive pul-monary disease induced by cigarette smoke or PM2.5. Ann Transl Med, 10(6):277.
16. Jiang XQ, Mei XD, Feng D (2016). Air pol-lution and chronic airway diseases: What should people know and do? J Thorac Dis, 8(1):E31-40.
17. Johannson KA, Vittinghoff E, Morisset J, et al (2018). Air Pollution Exposure Is As-sociated With Lower Lung Function, but Not Changes in Lung Function, in Pa-tients With Idiopathic Pulmonary Fibro-sis. Chest, 154(1):119-125.
18. Wang M, Zhang Y, Xu M, et al (2019). Roles of TRPA1 and TRPV1 in cigarette smoke -induced airway epithelial cell in-jury model. Free Radic Biol Med, 134:229-38.
19. Shan H, Li X, Ouyang C, et al (2022). Sali-droside prevents PM2.5-induced BEAS-2B cell apoptosis via SIRT1-dependent regulation of ROS and mitochondrial function. Ecotoxicol Environ Saf, 231:113170.
20. Shi J, Li F, Luo M, et al (2017). Distinct Roles of Wnt/β-Catenin signaling in the Pathogenesis of Chronic Obstructive Pulmonary Disease and Idiopathic Pul-monary Fibrosis. Mediators Inflamm, 2017:3520581.
21. Li R, Kou X, Geng H, et al (2015). Mito-chondrial damage: An important mech-anism of ambient PM2.5 exposure-induced acute heart injury in rats. J Hazard Mater, 287:392-401.
22. Sotty J, Kluza J, De Sousa C, et al (2020). Mitochondrial alterations triggered by repeated exposure to fine (PM2.5-0.18) and quasi-ultrafine (PM0.18) fractions of ambient particulate matter. Environ Int, 142:105830.
23. Chew S, Kolosowska N, Saveleva L, et al (2020). Impairment of mitochondrial function by particulate matter: Implica-tions for the brain. Neurochem Int, 135:104694.
24. Guo Z, Hong Z, Dong W, et al (2017). PM2.5-Induced Oxidative Stress and Mi-tochondrial Damage in the Nasal Mu-cosa of Rats. Int J Environ Res Public Health, 14(2):134.
25. Pak O, Scheibe S, Esfandiary A, et al (2018). Impact of the mitochondria-targeted an-tioxidant MitoQ on hypoxia-induced pulmonary hypertension. Eur Respir J, 51(3):1701024.
26. Li R, Ren T, Zeng J (2019). Mitochondrial Coenzyme Q Protects Sepsis-Induced Acute Lung Injury by Activating PI3K/Akt/GSK-3β/mTOR Pathway in Rats. Biomed Res Int, 2019: 5240898.
27. Hou L, Zhang J, Liu Y, et al (2021). MitoQ alleviates LPS-mediated acute lung injury through regulating Nrf2/Drp1 pathway. Free Radic Biol Med, 165:219-28.
28. Cen M, Ouyang W, Zhang W, et al (2021). MitoQ protects against hyperpermeabil-ity of endothelium barrier in acute lung injury via an Nrf2-dependent mecha-nism. Redox Biol, 41:101936.
29. Visalli G, Baluce B, Bertuccio M, et al (2015). Mitochondrial-Mediated Apopto-sis Pathway in Alveolar Epithelial Cells Exposed to the Metals in Combustion-Generated Particulate Matter. J Toxicol Environ Health A, 78(11):697-709.
30. Widden H, Placzek WJ (2021). The multiple mechanisms of MCL1 in the regulation of cell fate. Commun Biol, 4(1):1029.
31. Aghaei-Zarch SM, Alipourfard I, Rasoulza-deh H, et al (2023) A. Non-coding RNAs: An emerging player in particulate matter 2.5-mediated toxicity. Int J Biol Macromol, 235:123790.
32. Lin Q, Zhang C, Weng H, et al (2023). The utility of long non-coding RNAs in chronic obstructive pulmonary disease: A comprehensive analysis. BMC Pulm Med, 23(1):340.
33. Kim S, Song J, Ernst P, et al (2020). MitoQ regulates redox-related noncoding RNAs to preserve mitochondrial net-work integrity in pressure-overload heart failure. Am J Physiol Heart Circ Physiol, 318(3):H682-H695.
34. Song R, Dasgupta C, Mulder C, et al (2022). MicroRNA-210 Controls Mitochondrial Metabolism and Protects Heart Function in Myocardial Infarction. Circulation, 145(15):1140-1153.
35. Yaylım İ, Farooqi AA, Telkoparan-Akillilar P, et al (2023). Interplay between Non-Coding RNAs and NRF2 in Different Cancers: Spotlight on MicroRNAs and Long Non-Coding RNAs. J Pharmacol Exp Ther, 384(1):28-34.
36. Masoumi-Ardakani Y, Najafipour H, Nasri HR, et al (2022). Effect of Combined Endurance Training and MitoQ on Cardiac Function and Serum Level of Antioxidants, NO, miR-126, and miR-27a in Hypertensive Individuals. Biomed Res Int, 2022:8720661.
37. Rossman MJ, Santos-Parker JR, Steward CAC, et al (2018). Chronic Supplementa-tion With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults. Hypertension, 71(6):1056-1063.
38. Murray KO, Ludwig KR, Darvish S, et al (2023). Chronic mitochondria antioxi-dant treatment in older adults alters the circulating milieu to improve endotheli-al cell function and mitochondrial oxi-dative stress. Am J Physiol Heart Circ Phys-iol, 325(1):H187-H194.
39. Petcherski A, Sharma M, Satta S, et al (2022). Mitoquinone mesylate targets SARS-CoV-2 infection in preclinical models. bioRxiv, 2022.02.22.481100. [Preprint]
40. Murphy MP (2009). How mitochondria produce reactive oxygen species. Biochem J, 417(1):1-13.
41. Kauffman ME, Kauffman MK, Traore K, et al (2016). MitoSOX-Based Flow Cytome-try for Detecting Mitochondrial ROS. React Oxyg Species (Apex), 2(5):361-70.
2. Hu G, Zhong N, Ran P (2015). Air pollution and COPD in China. J Thorac Dis, 7(1):59-66.
3. Kaur M, Chandel J, Malik J, et al (2022). Particulate matter in COPD pathogene-sis: An overview. Inflamm Res, 71(7-8):797-815.
4. Leclercq B, Kluza J, Antherieu S, et al (2018). Air pollution-derived PM2.5 im-pairs mitochondrial function in healthy and chronic obstructive pulmonary dis-eased human bronchial epithelial cells. Environ Pollut, 243(Pt B):1434-49.
5. Song C, He J, Wu L, et al (2017). Health burden attributable to ambient PM2.5 in China. Environ Pollut, 223:575-86.
6. Xing YF, Xu YH, Shi MH, et al (2016). The impact of PM2.5 on the human respira-tory system. J Thorac Dis, 8(1):E69-74.
7. Wang Y, Zhong Y, Liao J, et al (2021). PM2.5-related cell death patterns. Int J Med Sci, 18(4):1024-9.
8. Deng X, Zhang F, Rui W, et al (2013). PM2.5-induced oxidative stress triggers autophagy in human lung epithelial A549 cells. Toxicol In Vitro, 27(6):1762-70.
9. Leclercq B, Kluza J, Anthérieu S, et al (2018). Mitochondrion: A critical target for the toxicity of air pollution-derived PM2.5 in healthy and COPD human bronchial epithelial cells. Eur Respir J, 52(suppl 62):PA1201.
10. Liu X, Zhao X, Li X, et al (2020). PM2.5 triggered apoptosis in lung epithelial cells through the mitochondrial apop-totic way mediated by a ROS-DRP1-mitochondrial fission axis. J Hazard Ma-ter, 397:122608.
11. Zinovkin RA, Zamyatnin AA (2019). Mito-chondria-Targeted Drugs. Curr Mol Pharmacol, 12(3):202-14.
12. Smith RAJ, Murphy MP (2010). Animal and human studies with the mitochondria-targeted antioxidant MitoQ. Ann N Y Acad Sci, 1201:96-103.
13. Cui L, Zhou Q, Zheng X, et al (2020). Mi-toQuinone attenuates vascular calcifica-tion by suppressing oxidative stress and reducing apoptosis of vascular smooth muscle cells via the Keap1/Nrf2 path-way. Free Radic Biol Med, 161:23-31.
14. Liu C, Sun Z, Wang M, et al (2022). Mi-toQuinone mitigates paraquat-induced A549 lung epithelial cell injury by pro-moting MFN1/MFN2-mediated mito-chondrial fusion. J Biochem Mol Toxicol, 36(9):e23127.
15. Lin Q, Zhang CF, Guo JL, et al (2022). In-volvement of NEAT1/PINK1-mediated mitophagy in chronic obstructive pul-monary disease induced by cigarette smoke or PM2.5. Ann Transl Med, 10(6):277.
16. Jiang XQ, Mei XD, Feng D (2016). Air pol-lution and chronic airway diseases: What should people know and do? J Thorac Dis, 8(1):E31-40.
17. Johannson KA, Vittinghoff E, Morisset J, et al (2018). Air Pollution Exposure Is As-sociated With Lower Lung Function, but Not Changes in Lung Function, in Pa-tients With Idiopathic Pulmonary Fibro-sis. Chest, 154(1):119-125.
18. Wang M, Zhang Y, Xu M, et al (2019). Roles of TRPA1 and TRPV1 in cigarette smoke -induced airway epithelial cell in-jury model. Free Radic Biol Med, 134:229-38.
19. Shan H, Li X, Ouyang C, et al (2022). Sali-droside prevents PM2.5-induced BEAS-2B cell apoptosis via SIRT1-dependent regulation of ROS and mitochondrial function. Ecotoxicol Environ Saf, 231:113170.
20. Shi J, Li F, Luo M, et al (2017). Distinct Roles of Wnt/β-Catenin signaling in the Pathogenesis of Chronic Obstructive Pulmonary Disease and Idiopathic Pul-monary Fibrosis. Mediators Inflamm, 2017:3520581.
21. Li R, Kou X, Geng H, et al (2015). Mito-chondrial damage: An important mech-anism of ambient PM2.5 exposure-induced acute heart injury in rats. J Hazard Mater, 287:392-401.
22. Sotty J, Kluza J, De Sousa C, et al (2020). Mitochondrial alterations triggered by repeated exposure to fine (PM2.5-0.18) and quasi-ultrafine (PM0.18) fractions of ambient particulate matter. Environ Int, 142:105830.
23. Chew S, Kolosowska N, Saveleva L, et al (2020). Impairment of mitochondrial function by particulate matter: Implica-tions for the brain. Neurochem Int, 135:104694.
24. Guo Z, Hong Z, Dong W, et al (2017). PM2.5-Induced Oxidative Stress and Mi-tochondrial Damage in the Nasal Mu-cosa of Rats. Int J Environ Res Public Health, 14(2):134.
25. Pak O, Scheibe S, Esfandiary A, et al (2018). Impact of the mitochondria-targeted an-tioxidant MitoQ on hypoxia-induced pulmonary hypertension. Eur Respir J, 51(3):1701024.
26. Li R, Ren T, Zeng J (2019). Mitochondrial Coenzyme Q Protects Sepsis-Induced Acute Lung Injury by Activating PI3K/Akt/GSK-3β/mTOR Pathway in Rats. Biomed Res Int, 2019: 5240898.
27. Hou L, Zhang J, Liu Y, et al (2021). MitoQ alleviates LPS-mediated acute lung injury through regulating Nrf2/Drp1 pathway. Free Radic Biol Med, 165:219-28.
28. Cen M, Ouyang W, Zhang W, et al (2021). MitoQ protects against hyperpermeabil-ity of endothelium barrier in acute lung injury via an Nrf2-dependent mecha-nism. Redox Biol, 41:101936.
29. Visalli G, Baluce B, Bertuccio M, et al (2015). Mitochondrial-Mediated Apopto-sis Pathway in Alveolar Epithelial Cells Exposed to the Metals in Combustion-Generated Particulate Matter. J Toxicol Environ Health A, 78(11):697-709.
30. Widden H, Placzek WJ (2021). The multiple mechanisms of MCL1 in the regulation of cell fate. Commun Biol, 4(1):1029.
31. Aghaei-Zarch SM, Alipourfard I, Rasoulza-deh H, et al (2023) A. Non-coding RNAs: An emerging player in particulate matter 2.5-mediated toxicity. Int J Biol Macromol, 235:123790.
32. Lin Q, Zhang C, Weng H, et al (2023). The utility of long non-coding RNAs in chronic obstructive pulmonary disease: A comprehensive analysis. BMC Pulm Med, 23(1):340.
33. Kim S, Song J, Ernst P, et al (2020). MitoQ regulates redox-related noncoding RNAs to preserve mitochondrial net-work integrity in pressure-overload heart failure. Am J Physiol Heart Circ Physiol, 318(3):H682-H695.
34. Song R, Dasgupta C, Mulder C, et al (2022). MicroRNA-210 Controls Mitochondrial Metabolism and Protects Heart Function in Myocardial Infarction. Circulation, 145(15):1140-1153.
35. Yaylım İ, Farooqi AA, Telkoparan-Akillilar P, et al (2023). Interplay between Non-Coding RNAs and NRF2 in Different Cancers: Spotlight on MicroRNAs and Long Non-Coding RNAs. J Pharmacol Exp Ther, 384(1):28-34.
36. Masoumi-Ardakani Y, Najafipour H, Nasri HR, et al (2022). Effect of Combined Endurance Training and MitoQ on Cardiac Function and Serum Level of Antioxidants, NO, miR-126, and miR-27a in Hypertensive Individuals. Biomed Res Int, 2022:8720661.
37. Rossman MJ, Santos-Parker JR, Steward CAC, et al (2018). Chronic Supplementa-tion With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults. Hypertension, 71(6):1056-1063.
38. Murray KO, Ludwig KR, Darvish S, et al (2023). Chronic mitochondria antioxi-dant treatment in older adults alters the circulating milieu to improve endotheli-al cell function and mitochondrial oxi-dative stress. Am J Physiol Heart Circ Phys-iol, 325(1):H187-H194.
39. Petcherski A, Sharma M, Satta S, et al (2022). Mitoquinone mesylate targets SARS-CoV-2 infection in preclinical models. bioRxiv, 2022.02.22.481100. [Preprint]
40. Murphy MP (2009). How mitochondria produce reactive oxygen species. Biochem J, 417(1):1-13.
41. Kauffman ME, Kauffman MK, Traore K, et al (2016). MitoSOX-Based Flow Cytome-try for Detecting Mitochondrial ROS. React Oxyg Species (Apex), 2(5):361-70.
| Files | ||
| Issue | Vol 53 No 3 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v53i3.15143 | |
| Keywords | ||
| MitoQuinone Mitochondrial dynamics Mitochondrial-mediated apoptosis | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Weng A-B, Deng M-M, Liu X-D, Wang H-B, Lin Q. MitoQ Alleviated PM2.5 Induced Pulmonary Epithelial Cells Injury by Inhibiting Mitochondrial-Mediated Apoptosis. Iran J Public Health. 2024;53(3):614-624.
