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Quercetogetin protects against cigarette smoke extract-induced apoptosis in epithelial cells by inhibiting mitophagy.
Toxicol In Vitro. 2018 Apr; 48:170-178.TV

Abstract

Recent studies demonstrate that the autophagy-dependent turnover of mitochondria (mitophagy) mediates pulmonary epithelial cell death in response to cigarette smoke extract (CSE) exposure, and contributes to emphysema development in vivo during chronic cigarette smoke (CS)-exposure, although the underlying mechanisms remain unclear. Here, we investigated the role of mitophagy in regulating apoptosis in CSE-exposed human lung bronchial epithelial cells. Furthermore, we investigated the potential of the polymethoxylated flavone antioxidant quercetogetin (QUE) to inhibit CSE-induced mitophagy-dependent apoptosis. Our results demonstrate that CSE induces mitophagy in epithelial cells via mitochondrial dysfunction, and causes increased expression levels of the mitophagy-regulator protein PTEN-induced putative kinase-1 (PINK1) and the mitochondrial fission protein dynamin-1-like protein (DRP-1). CSE induced epithelial cell death and increased the expression of the apoptosis-related proteins cleaved caspase-3, -8 and -9. Caspase-3 activity was significantly increased in Beas-2B cells exposed to CSE, and decreased by siRNA-dependent knockdown of DRP-1. Treatment of epithelial cells with QUE inhibited CSE-induced mitochondrial dysfunction and mitophagy by inhibiting phospho (p)-DRP-1 and PINK1 expression. QUE suppressed mitophagy-dependent apoptosis by inhibiting the expression of cleaved caspase-3, -8 and -9 and downregulating caspase activity in human bronchial epithelial cells. These findings suggest that QUE may serve as a potential therapeutic in CS-induced pulmonary diseases.

Authors+Show Affiliations

Division of Pulmonology and Allergy, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea; Department of Biomedical Chemistry, KonKuk University, Chungju 27478, Republic of Korea.Gachon Medical Research Institute, Gachon University Gil Medical Center, Incheon, Republic of Korea.Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, NY, USA.Department of Biochemistry, College of Medicine, Gachon University, Incheon, Republic of Korea.Division of Pulmonology and Allergy, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea.Division of Pulmonology and Allergy, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea.Division of Pulmonology and Allergy, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea.Department of Biomedical Chemistry, KonKuk University, Chungju 27478, Republic of Korea.Division of Pulmonology and Allergy, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea. Electronic address: jwpark@gilhospital.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29391262

Citation

Son, Eun Suk, et al. "Quercetogetin Protects Against Cigarette Smoke Extract-induced Apoptosis in Epithelial Cells By Inhibiting Mitophagy." Toxicology in Vitro : an International Journal Published in Association With BIBRA, vol. 48, 2018, pp. 170-178.
Son ES, Kim SH, Ryter SW, et al. Quercetogetin protects against cigarette smoke extract-induced apoptosis in epithelial cells by inhibiting mitophagy. Toxicol In Vitro. 2018;48:170-178.
Son, E. S., Kim, S. H., Ryter, S. W., Yeo, E. J., Kyung, S. Y., Kim, Y. J., Jeong, S. H., Lee, C. S., & Park, J. W. (2018). Quercetogetin protects against cigarette smoke extract-induced apoptosis in epithelial cells by inhibiting mitophagy. Toxicology in Vitro : an International Journal Published in Association With BIBRA, 48, 170-178. https://doi.org/10.1016/j.tiv.2018.01.011
Son ES, et al. Quercetogetin Protects Against Cigarette Smoke Extract-induced Apoptosis in Epithelial Cells By Inhibiting Mitophagy. Toxicol In Vitro. 2018;48:170-178. PubMed PMID: 29391262.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quercetogetin protects against cigarette smoke extract-induced apoptosis in epithelial cells by inhibiting mitophagy. AU - Son,Eun Suk, AU - Kim,Se-Hee, AU - Ryter,Stefan W, AU - Yeo,Eui-Ju, AU - Kyung,Sun Young, AU - Kim,Yu Jin, AU - Jeong,Sung Hwan, AU - Lee,Chang Soo, AU - Park,Jeong-Woong, Y1 - 2018/01/31/ PY - 2017/09/18/received PY - 2017/12/11/revised PY - 2018/01/15/accepted PY - 2018/2/3/pubmed PY - 2018/9/19/medline PY - 2018/2/3/entrez KW - Apoptosis KW - COPD KW - Cigarette smoke KW - Mitophagy KW - Quercetogetin SP - 170 EP - 178 JF - Toxicology in vitro : an international journal published in association with BIBRA JO - Toxicol In Vitro VL - 48 N2 - Recent studies demonstrate that the autophagy-dependent turnover of mitochondria (mitophagy) mediates pulmonary epithelial cell death in response to cigarette smoke extract (CSE) exposure, and contributes to emphysema development in vivo during chronic cigarette smoke (CS)-exposure, although the underlying mechanisms remain unclear. Here, we investigated the role of mitophagy in regulating apoptosis in CSE-exposed human lung bronchial epithelial cells. Furthermore, we investigated the potential of the polymethoxylated flavone antioxidant quercetogetin (QUE) to inhibit CSE-induced mitophagy-dependent apoptosis. Our results demonstrate that CSE induces mitophagy in epithelial cells via mitochondrial dysfunction, and causes increased expression levels of the mitophagy-regulator protein PTEN-induced putative kinase-1 (PINK1) and the mitochondrial fission protein dynamin-1-like protein (DRP-1). CSE induced epithelial cell death and increased the expression of the apoptosis-related proteins cleaved caspase-3, -8 and -9. Caspase-3 activity was significantly increased in Beas-2B cells exposed to CSE, and decreased by siRNA-dependent knockdown of DRP-1. Treatment of epithelial cells with QUE inhibited CSE-induced mitochondrial dysfunction and mitophagy by inhibiting phospho (p)-DRP-1 and PINK1 expression. QUE suppressed mitophagy-dependent apoptosis by inhibiting the expression of cleaved caspase-3, -8 and -9 and downregulating caspase activity in human bronchial epithelial cells. These findings suggest that QUE may serve as a potential therapeutic in CS-induced pulmonary diseases. SN - 1879-3177 UR - https://www.unboundmedicine.com/medline/citation/29391262/Quercetogetin_protects_against_cigarette_smoke_extract_induced_apoptosis_in_epithelial_cells_by_inhibiting_mitophagy_ DB - PRIME DP - Unbound Medicine ER -