Tags

Type your tag names separated by a space and hit enter

Daphnetin-mediated Nrf2 antioxidant signaling pathways ameliorate tert-butyl hydroperoxide (t-BHP)-induced mitochondrial dysfunction and cell death.
Free Radic Biol Med. 2017 05; 106:38-52.FR

Abstract

Daphnetin (Daph), a natural coumarin derivative isolated from plants of the Genus Daphne, possesses abundant biological activities, such as anti-inflammatory, antioxidant and anticancer properties. In the present study, we focused on investigating the protective effect of Daph against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage, mitochondrial dysfunction and the involvement of underlying molecular mechanisms. Our findings indicated that Daph effectively inhibited t-BHP-stimulated cytotoxicity, cell apoptosis, and mitochondrial dysfunction, which are associated with suppressed reactive oxygen species (ROS) generation, decreased malondialdehyde (MDA) formation, increased superoxide dismutase (SOD) levels and glutathione (GSH)/GSSG (oxidized GSH) ratio. Further investigation indicated that Daph significantly suppressed cytochrome c release and NLRP3 inflammasome activation and modulated apoptosis-related protein Bcl-2, Bax, and caspase-3 expression. Moreover, Daph dramatically induced the expression of the glutamate-cysteine ligase modifier (GCLM) subunit and the glutamate-cysteine ligase catalytic (GCLC) subunit, heme oxygenase-1 (HO-1), and NAD (P) H: quinone oxidoreductase (NQO1), which is largely dependent on upregulating the nuclear factor-erythroid 2-related factor 2 (Nrf2) nuclear translocation, reducing the Keap1 protein expression, and strengthening the antioxidant response element (ARE) promoter activity. Additionally, Daph remarkably activated a c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) phosphorylation, but ERK and JNK inhibitor pretreatment exhibited an evident decrease of the level of Daph-enhanced Nrf2 nuclear translocation. Furthermore, Daph exposure suppressed t-BHP-induced cytotoxicity and ROS overproduction, which are mostly blocked in Nrf2 knockout RAW 264.7 cells and peritoneal macrophages. Accordingly, Daph exhibited protective roles against t-BHP-triggered oxidative damage and mitochondrial dysfunction by the upregulation of Nrf2 antioxidant signaling pathways, which may be involved in the activation of JNK and ERK.

Authors+Show Affiliations

Institute of Translational Medicine, The First Hospital, Jilin University, Changchun 130001, China; Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine. Jilin University, Changchun 130061, China.Institute of Translational Medicine, The First Hospital, Jilin University, Changchun 130001, China.Institute of Translational Medicine, The First Hospital, Jilin University, Changchun 130001, China.Institute of Translational Medicine, The First Hospital, Jilin University, Changchun 130001, China.Institute of Translational Medicine, The First Hospital, Jilin University, Changchun 130001, China; Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine. Jilin University, Changchun 130061, China.Institute of Translational Medicine, The First Hospital, Jilin University, Changchun 130001, China. Electronic address: cixinxin@jlu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28188924

Citation

Lv, Hongming, et al. "Daphnetin-mediated Nrf2 Antioxidant Signaling Pathways Ameliorate Tert-butyl Hydroperoxide (t-BHP)-induced Mitochondrial Dysfunction and Cell Death." Free Radical Biology & Medicine, vol. 106, 2017, pp. 38-52.
Lv H, Liu Q, Zhou J, et al. Daphnetin-mediated Nrf2 antioxidant signaling pathways ameliorate tert-butyl hydroperoxide (t-BHP)-induced mitochondrial dysfunction and cell death. Free Radic Biol Med. 2017;106:38-52.
Lv, H., Liu, Q., Zhou, J., Tan, G., Deng, X., & Ci, X. (2017). Daphnetin-mediated Nrf2 antioxidant signaling pathways ameliorate tert-butyl hydroperoxide (t-BHP)-induced mitochondrial dysfunction and cell death. Free Radical Biology & Medicine, 106, 38-52. https://doi.org/10.1016/j.freeradbiomed.2017.02.016
Lv H, et al. Daphnetin-mediated Nrf2 Antioxidant Signaling Pathways Ameliorate Tert-butyl Hydroperoxide (t-BHP)-induced Mitochondrial Dysfunction and Cell Death. Free Radic Biol Med. 2017;106:38-52. PubMed PMID: 28188924.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Daphnetin-mediated Nrf2 antioxidant signaling pathways ameliorate tert-butyl hydroperoxide (t-BHP)-induced mitochondrial dysfunction and cell death. AU - Lv,Hongming, AU - Liu,Qinmei, AU - Zhou,Junfeng, AU - Tan,Guangyun, AU - Deng,Xuming, AU - Ci,Xinxin, Y1 - 2017/02/07/ PY - 2016/11/04/received PY - 2017/01/25/revised PY - 2017/02/06/accepted PY - 2017/2/12/pubmed PY - 2017/12/16/medline PY - 2017/2/12/entrez KW - Daphnetin KW - Mitochondrial dysfunction KW - Nrf2 KW - Oxidative damage KW - ROS SP - 38 EP - 52 JF - Free radical biology & medicine JO - Free Radic. Biol. Med. VL - 106 N2 - Daphnetin (Daph), a natural coumarin derivative isolated from plants of the Genus Daphne, possesses abundant biological activities, such as anti-inflammatory, antioxidant and anticancer properties. In the present study, we focused on investigating the protective effect of Daph against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage, mitochondrial dysfunction and the involvement of underlying molecular mechanisms. Our findings indicated that Daph effectively inhibited t-BHP-stimulated cytotoxicity, cell apoptosis, and mitochondrial dysfunction, which are associated with suppressed reactive oxygen species (ROS) generation, decreased malondialdehyde (MDA) formation, increased superoxide dismutase (SOD) levels and glutathione (GSH)/GSSG (oxidized GSH) ratio. Further investigation indicated that Daph significantly suppressed cytochrome c release and NLRP3 inflammasome activation and modulated apoptosis-related protein Bcl-2, Bax, and caspase-3 expression. Moreover, Daph dramatically induced the expression of the glutamate-cysteine ligase modifier (GCLM) subunit and the glutamate-cysteine ligase catalytic (GCLC) subunit, heme oxygenase-1 (HO-1), and NAD (P) H: quinone oxidoreductase (NQO1), which is largely dependent on upregulating the nuclear factor-erythroid 2-related factor 2 (Nrf2) nuclear translocation, reducing the Keap1 protein expression, and strengthening the antioxidant response element (ARE) promoter activity. Additionally, Daph remarkably activated a c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) phosphorylation, but ERK and JNK inhibitor pretreatment exhibited an evident decrease of the level of Daph-enhanced Nrf2 nuclear translocation. Furthermore, Daph exposure suppressed t-BHP-induced cytotoxicity and ROS overproduction, which are mostly blocked in Nrf2 knockout RAW 264.7 cells and peritoneal macrophages. Accordingly, Daph exhibited protective roles against t-BHP-triggered oxidative damage and mitochondrial dysfunction by the upregulation of Nrf2 antioxidant signaling pathways, which may be involved in the activation of JNK and ERK. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/28188924/Daphnetin_mediated_Nrf2_antioxidant_signaling_pathways_ameliorate_tert_butyl_hydroperoxide__t_BHP__induced_mitochondrial_dysfunction_and_cell_death_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(17)30076-X DB - PRIME DP - Unbound Medicine ER -