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Chlorogenic acid prevents paraquat-induced apoptosis via Sirt1-mediated regulation of redox and mitochondrial function.
Free Radic Res. 2019 Jun; 53(6):680-693.FR

Abstract

Paraquat (PQ) is a widely used agro-chemical in agriculture and highly toxic to humans. Although the mechanism of PQ poisoning is not clear, it has been well documented that reactive oxygen species (ROS) generation and apoptosis play pivotal roles. Alternatively, chlorogenic acid (CA) is a biologically active dietary polyphenol, playing several therapeutic roles. However, it is not known whether CA has protective effect on PQ-induced apoptosis. Here, we investigated the effect of CA in preventing PQ-induced apoptosis and explored the underlying mechanisms. A549 cells were pretreated with 100 µM CA for 24 h and then exposed to 160 µM PQ for 24 h. We found that CA was effective in preventing PQ-induced apoptotic features, including the release of cytochrome c from the mitochondria to cytoplasm, the cleavages of caspase 3 and caspase 9, and the increases in levels of Bcl-2-associated X protein (Bax) and intracellular calcium ions. CA alleviated ROS production and prevented the reduction of antioxidant capacity in cells exposed to PQ by increasing NF-E2-related factor 2 (Nrf2), superoxide dismutase 2 (SOD2) and glutathione levels. In addition, CA also attenuated PQ-induced alterations of mitochondrial structure and function (such as the decreases in membrane potential and adenosine triphosphate level), and the impaired autophagic flux was improved by CA. Down-regulation of sirtuin 1 (Sirt1) by short hairpin RNA reversed the protective effects of CA. Thus, CA may be viewed as a potential drug to treat PQ-induced lung epithelial cell apoptosis and other disorders with similar pathologic mechanisms.

Authors+Show Affiliations

a Department of Toxicology, The Ministry of Education, Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, School of Public Health , Air Force Medical University (Fourth Military Medical University) , Xi'an , PR China.b Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Jiangsu National Synergistic Innovation Center for Advanced Materials (SICAM) , Nanjing Tech University (NanjingTech) , Nanjing , PR China.a Department of Toxicology, The Ministry of Education, Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, School of Public Health , Air Force Medical University (Fourth Military Medical University) , Xi'an , PR China.a Department of Toxicology, The Ministry of Education, Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, School of Public Health , Air Force Medical University (Fourth Military Medical University) , Xi'an , PR China.a Department of Toxicology, The Ministry of Education, Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, School of Public Health , Air Force Medical University (Fourth Military Medical University) , Xi'an , PR China.a Department of Toxicology, The Ministry of Education, Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, School of Public Health , Air Force Medical University (Fourth Military Medical University) , Xi'an , PR China.a Department of Toxicology, The Ministry of Education, Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, School of Public Health , Air Force Medical University (Fourth Military Medical University) , Xi'an , PR China.a Department of Toxicology, The Ministry of Education, Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, School of Public Health , Air Force Medical University (Fourth Military Medical University) , Xi'an , PR China.b Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Jiangsu National Synergistic Innovation Center for Advanced Materials (SICAM) , Nanjing Tech University (NanjingTech) , Nanjing , PR China.a Department of Toxicology, The Ministry of Education, Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, School of Public Health , Air Force Medical University (Fourth Military Medical University) , Xi'an , PR China.a Department of Toxicology, The Ministry of Education, Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, School of Public Health , Air Force Medical University (Fourth Military Medical University) , Xi'an , PR China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31106605

Citation

Kong, Deqin, et al. "Chlorogenic Acid Prevents Paraquat-induced Apoptosis Via Sirt1-mediated Regulation of Redox and Mitochondrial Function." Free Radical Research, vol. 53, no. 6, 2019, pp. 680-693.
Kong D, Ding Y, Liu J, et al. Chlorogenic acid prevents paraquat-induced apoptosis via Sirt1-mediated regulation of redox and mitochondrial function. Free Radic Res. 2019;53(6):680-693.
Kong, D., Ding, Y., Liu, J., Liu, R., Zhang, J., Zhou, Q., Long, Z., Peng, J., Li, L., Bai, H., & Hai, C. (2019). Chlorogenic acid prevents paraquat-induced apoptosis via Sirt1-mediated regulation of redox and mitochondrial function. Free Radical Research, 53(6), 680-693. https://doi.org/10.1080/10715762.2019.1621308
Kong D, et al. Chlorogenic Acid Prevents Paraquat-induced Apoptosis Via Sirt1-mediated Regulation of Redox and Mitochondrial Function. Free Radic Res. 2019;53(6):680-693. PubMed PMID: 31106605.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chlorogenic acid prevents paraquat-induced apoptosis via Sirt1-mediated regulation of redox and mitochondrial function. AU - Kong,Deqin, AU - Ding,Yaqi, AU - Liu,Jiangzheng, AU - Liu,Rui, AU - Zhang,Jiaxin, AU - Zhou,Qingbiao, AU - Long,Zi, AU - Peng,Jie, AU - Li,Lin, AU - Bai,Hua, AU - Hai,Chunxu, Y1 - 2019/06/04/ PY - 2019/5/21/pubmed PY - 2019/12/21/medline PY - 2019/5/21/entrez KW - Apoptosis KW - chlorogenic acid KW - mitochondria KW - paraquat KW - reactive oxygen species SP - 680 EP - 693 JF - Free radical research JO - Free Radic. Res. VL - 53 IS - 6 N2 - Paraquat (PQ) is a widely used agro-chemical in agriculture and highly toxic to humans. Although the mechanism of PQ poisoning is not clear, it has been well documented that reactive oxygen species (ROS) generation and apoptosis play pivotal roles. Alternatively, chlorogenic acid (CA) is a biologically active dietary polyphenol, playing several therapeutic roles. However, it is not known whether CA has protective effect on PQ-induced apoptosis. Here, we investigated the effect of CA in preventing PQ-induced apoptosis and explored the underlying mechanisms. A549 cells were pretreated with 100 µM CA for 24 h and then exposed to 160 µM PQ for 24 h. We found that CA was effective in preventing PQ-induced apoptotic features, including the release of cytochrome c from the mitochondria to cytoplasm, the cleavages of caspase 3 and caspase 9, and the increases in levels of Bcl-2-associated X protein (Bax) and intracellular calcium ions. CA alleviated ROS production and prevented the reduction of antioxidant capacity in cells exposed to PQ by increasing NF-E2-related factor 2 (Nrf2), superoxide dismutase 2 (SOD2) and glutathione levels. In addition, CA also attenuated PQ-induced alterations of mitochondrial structure and function (such as the decreases in membrane potential and adenosine triphosphate level), and the impaired autophagic flux was improved by CA. Down-regulation of sirtuin 1 (Sirt1) by short hairpin RNA reversed the protective effects of CA. Thus, CA may be viewed as a potential drug to treat PQ-induced lung epithelial cell apoptosis and other disorders with similar pathologic mechanisms. SN - 1029-2470 UR - https://www.unboundmedicine.com/medline/citation/31106605/Chlorogenic_acid_prevents_paraquat_induced_apoptosis_via_Sirt1_mediated_regulation_of_redox_and_mitochondrial_function_ L2 - http://www.tandfonline.com/doi/full/10.1080/10715762.2019.1621308 DB - PRIME DP - Unbound Medicine ER -