Eupatilin induces Sestrin2-dependent autophagy to prevent oxidative stress
详细信息 查看全文
- 作者：Kyung Hwan Jegal ; Hae Li Ko ; Sang Mi Park ; Sung Hui Byun ; Keon Wook Kang…
- 关键词：Eupatilin ; Sestrin ; 2 ; Autophagy ; Cytoprotection ; Oxidative stress
- 刊名：Apoptosis
- 出版年：2016
- 出版时间：May 2016
- 年：2016
- 卷：21
- 期：5
- 页码：642-656
- 全文大小：2,176 KB
- 参考文献：1.Malhi H, Guicciardi ME, Gores GJ (2010) Hepatocyte death: a clear and present danger. Physiol Rev 90:1165–1194. doi:10.1152/physrev.00061.2009 CrossRef PubMed PubMedCentral
2.Balboa MA, Balsinde J (2006) Oxidative stress and arachidonic acid mobilization. Biochim Biophys Acta 1761:385–391. doi:10.1016/j.bbalip.2006.03.014 CrossRef PubMed
3.Scorrano L, Penzo D, Petronilli V et al (2001) Arachidonic acid causes cell death through the mitochondrial permeability transition. Implications for tumor necrosis factor-alpha apoptotic signaling. J Biol Chem 276:12035–12040. doi:10.1074/jbc.M010603200 CrossRef PubMed
4.Cederbaum AI (2003) Iron and CYP2E1-dependent oxidative stress and toxicity. Alcohol 30:115–120. doi:10.1016/S0741-8329(03)00104-6 CrossRef PubMed
5.Choi AMK, Ryter SW, Levine B (2013) Autophagy in human health and disease. N Engl J Med 368:651–662. doi:10.1056/NEJMra1205406 CrossRef PubMed
6.Mortimore GE, Pösö AR, Lardeux BR (1989) Mechanism and regulation of protein degradation in liver. Diabetes Metab Rev 5:49–70. doi:10.1002/dmr.5610050105 CrossRef PubMed
7.Rautou PE, Mansouri A, Lebrec D et al (2010) Autophagy in liver diseases. J Hepatol 53:1123–1134. doi:10.1016/j.jhep.2010.07.006 CrossRef PubMed
8.Kim JS, Nitta T, Mohuczy D et al (2008) Impaired autophagy: a mechanism of mitochondrial dysfunction in anoxic rat hepatocytes. Hepatology 47:1725–1736. doi:10.1002/hep.22187 CrossRef PubMed PubMedCentral
9.Sir D, Tian Y, Chen WL et al (2010) The early autophagic pathway is activated by hepatitis B virus and required for viral DNA replication. Proc Natl Acad Sci USA 107:4383–4388. doi:10.1073/pnas.0911373107 CrossRef PubMed PubMedCentral
10.Dreux M, Gastaminza P, Wieland SF, Chisari FV (2009) The autophagy machinery is required to initiate hepatitis C virus replication. Proc Natl Acad Sci USA 106:14046–14051. doi:10.1073/pnas.0907344106 CrossRef PubMed PubMedCentral
11.Ding ZB, Shi YH, Zhou J et al (2008) Association of autophagy defect with a malignant phenotype and poor prognosis of hepatocellular carcinoma. Cancer Res 68:9167–9175. doi:10.1158/0008-5472.CAN-08-1573 CrossRef PubMed
12.Budanov AV, Shoshani T, Faerman A et al (2002) Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability. Oncogene 21:6017–6031. doi:10.1038/sj.onc.1205877 CrossRef PubMed
13.Lee JH, Budanov AV, Karin M (2013) Sestrins orchestrate cellular metabolism to attenuate aging. Cell Metab 18:792–801. doi:10.1016/j.cmet.2013.08.018 CrossRef PubMed
14.Budanov AV, Karin M (2008) p53 target genes Sestrin1 and Sestrin2 connect genotoxic stress and mTOR signaling. Cell 134:451–460. doi:10.1016/j.cell.2008.06.028 CrossRef PubMed PubMedCentral
15.Parmigiani A, Nourbakhsh A, Ding B et al (2014) Sestrins inhibit mTORC1 kinase activation through the GATOR complex. Cell Rep 9:1281–1291. doi:10.1016/j.celrep.2014.10.019 CrossRef PubMed PubMedCentral
16.Maiuri MC, Malik SA, Morselli E et al (2009) Stimulation of autophagy by the p53 target gene Sestrin2. Cell Cycle 8:1571–1576. doi:10.4161/cc.8.10.8498 CrossRef PubMed
17.Shin BY, Jin SH, Cho IJ, Ki SH (2012) Nrf2-ARE pathway regulates induction of Sestrin-2 expression. Free Radic Biol Med 53:834–841. doi:10.1016/j.freeradbiomed.2012.06.026 CrossRef PubMed
18.Yang JH, Kim KM, Kim MG et al (2015) Role of sestrin2 in the regulation of proinflammatory signaling in macrophages. Free Radic Biol Med 78:156–167. doi:10.1016/j.freeradbiomed.2014.11.002 CrossRef PubMed
19.Lee JH, Budanov AV, Talukdar S et al (2012) Maintenance of metabolic homeostasis by Sestrin2 and Sestrin3. Cell Metab 16:311–321. doi:10.1016/j.cmet.2012.08.004 CrossRef PubMed PubMedCentral
20.Buitrago-Molina LE, Marhenke S, Longerich T et al (2013) The degree of liver injury determines the role of p21 in liver regeneration and hepatocarcinogenesis in mice. Hepatology 58:1143–1152. doi:10.1002/hep.26412 CrossRef PubMed
21.Cai M, Phan PT, Hong JG et al (2012) The neuroprotective effect of eupatilin against ischemia/reperfusion-induced delayed neuronal damage in mice. Eur J Pharmacol 689:104–110. doi:10.1016/j.ejphar.2012.05.042 CrossRef PubMed
22.Lee S, Lee M, Kim SH (2008) Eupatilin inhibits H2O2-induced apoptotic cell death through inhibition of mitogen-activated protein kinases and nuclear factor-κB. Food Chem Toxicol 46:2865–2870. doi:10.1016/j.fct.2008.05.026 CrossRef PubMed
23.Jeong JH, Moon SJ, Jhun JY et al (2015) Eupatilin exerts antinociceptive and chondroprotective properties in a rat model of osteoarthritis by downregulating oxidative damage and catabolic activity in chondrocytes. PLoS ONE 10:e0130882. doi:10.1371/journal.pone.0130882 CrossRef PubMed PubMedCentral
24.Min SW, Kim NJ, Baek NI, Kim DH (2009) Inhibitory effect of eupatilin and jaceosidin isolated from Artemisia princeps on carrageenan-induced inflammation in mice. J Ethnopharmacol 125:497–500. doi:10.1016/j.jep.2009.06.001 CrossRef PubMed
25.Son JE, Lee E, Seo SG et al (2013) Eupatilin, a major flavonoid of Artemisia, attenuates aortic smooth muscle cell proliferation and migration by inhibiting PI3K, MKK3/6, and MKK4 activities. Planta Med 79:1009–1016. doi:10.1055/s-0033-1350621 CrossRef PubMed
26.Cheong JH, Hong SY, Zheng Y, Noh SH (2011) Eupatilin inhibits gastric cancer cell growth by blocking STAT3-mediated VEGF expression. J Gastric Cancer 11:16–22. doi:10.5230/jgc.2011.11.1.16 CrossRef PubMed PubMedCentral
27.Seol SY, Kim MH, Ryu JS et al (2004) DA-9601 for erosive gastritis: results of a double-blind placebo-controlled phase III clinical trial. World J Gastroenterol 10:2379. doi:10.3748/wjg.v10.i16.2379 CrossRef PubMed PubMedCentral
28.Ryu BK, Ahn BO, Oh TY et al (1998) Studies on protective effect of DA-9601, Artemisia asiatica extract, on acetaminophen- and CCl4-induced liver damage in rats. Arch Pharm Res 21:508–513. doi:10.1007/BF02975366 CrossRef PubMed
29.Cheong JY, Oh TY, Lee KM et al (2002) Suppressive effects of antioxidant DA-9601 on hepatic fibrosis in rats. Taehan Kan Hakhoe chi 8:436–447PubMed
30.Park SC, Yoon JH, Kim W et al (2006) Eupatilin attenuates bile acid-induced hepatocyte apoptosis. J Gastroenterol 41:772–778. doi:10.1007/s00535-006-1854-6 CrossRef PubMed
31.Shin SM, Kim SG (2009) Inhibition of arachidonic acid and iron-induced mitochondrial dysfunction and apoptosis by oltipraz and novel 1,2-dithiole-3-thione congeners. Mol Pharmacol 75:242–253. doi:10.1124/mol.108.051128 CrossRef PubMed
32.Wang K, Liu R, Li J et al (2011) Quercetin induces protective autophagy in gastric cancer cells: involvement of Akt-mTOR- and hypoxia-induced factor 1α-mediated signaling. Autophagy 7:966–978. doi:10.4161/auto.7.9.15863 CrossRef PubMed
33.Nah J, Pyo JO, Jung S et al (2013) BECN1/Beclin 1 is recruited into lipid rafts by prion to activate autophagy in response to amyloid β 42. Autophagy 9:2009–2021. doi:10.4161/auto.26118 CrossRef PubMed
34.Dong GZ, Jang EJ, Kang SH et al (2013) Red ginseng abrogates oxidative stress via mitochondria protection mediated by LKB1-AMPK pathway. BMC Complement Altern Med 13:64. doi:10.1186/1472-6882-13-64 CrossRef PubMed PubMedCentral
35.Klionsky DJ, Abdalla FC, Abeliovich H et al (2012) Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8:445–544. doi:10.4161/auto.19496 CrossRef PubMed PubMedCentral
36.Yamamoto A, Tagawa Y, Yoshimori T et al (1998) Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells. Cell Struct Funct 23:33–42. doi:10.1247/csf.23.33 CrossRef PubMed
37.Ishihara M, Urushido M, Hamada K et al (2013) Sestrin-2 and BNIP3 regulate autophagy and mitophagy in renal tubular cells in acute kidney injury. Am J Physiol Renal Physiol 305:F495–F509. doi:10.1152/ajprenal.00642.2012 CrossRef PubMed
38.Seo K, Ki SH, Shin SM (2015) Sestrin2-AMPK activation protects mitochondrial function against glucose deprivation-induced cytotoxicity. Cell Signal 27:1533–1543. doi:10.1016/j.cellsig.2015.03.003 CrossRef PubMed
39.Gottlieb RA, Carreira RS (2010) Autophagy in health and disease. 5. Mitophagy as a way of life. Am J Physiol Cell Physiol 299:C203–C210. doi:10.1152/ajpcell.00097.2010 CrossRef PubMed PubMedCentral
40.Bhogal RH, Weston CJ, Curbishley SM et al (2012) Autophagy: a cyto-protective mechanism which prevents primary human hepatocyte apoptosis during oxidative stress. Autophagy 8:545–558. doi:10.4161/auto.19012 CrossRef PubMed PubMedCentral
41.Pankiv S, Clausen TH, Lamark T et al (2007) p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 282:24131–24145. doi:10.1074/jbc.M702824200 CrossRef PubMed
42.Wu D, Cederbaum AI (2013) Inhibition of autophagy promotes CYP2E1-dependent toxicity in HepG2 cells via elevated oxidative stress, mitochondria dysfunction and activation of p38 and JNK MAPK. Redox Biol 1:552–565. doi:10.1016/j.redox.2013.10.008 CrossRef PubMed PubMedCentral
43.Brüning A, Rahmeh M, Friese K (2013) Nelfinavir and bortezomib inhibit mTOR activity via ATF4-mediated sestrin-2 regulation. Mol Oncol 7:1012–1018. doi:10.1016/j.molonc.2013.07.010 CrossRef PubMed
44.Bae SH, Sung SH, Oh SY et al (2013) Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage. Cell Metab 17:73–84. doi:10.1016/j.cmet.2012.12.002 CrossRef PubMed
45.Song HJ, Shin CY, Oh TY et al (2009) Eupatilin with heme oxygenase-1-inducing ability protects cultured feline esophageal epithelial cells from cell damage caused by indomethacin. Biol Pharm Bull 32:589–596. doi:10.1248/bpb.32.589 CrossRef PubMed
46.Jin SH, Yang JH, Shin BY et al (2013) Resveratrol inhibits LXRα-dependent hepatic lipogenesis through novel antioxidant Sestrin2 gene induction. Toxicol Appl Pharmacol 271:95–105. doi:10.1016/j.taap.2013.04.023 CrossRef PubMed
47.Egan DF, Shackelford DB, Mihaylova MM et al (2011) Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331:456–461. doi:10.1126/science.1196371 CrossRef PubMed PubMedCentral
48.Ro SH, Semple IA, Park H et al (2014) Sestrin2 promotes Unc-51-like kinase 1 mediated phosphorylation of p62/sequestosome-1. FEBS J 281:3816–3827. doi:10.1111/febs.12905 CrossRef PubMed PubMedCentral
49.Zoncu R, Efeyan A, Sabatini DM (2011) mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 12:21–35. doi:10.1038/nrm3025 CrossRef PubMed PubMedCentral
50.Tee AR, Proud CG (2000) DNA-damaging agents cause inactivation of translational regulators linked to mTOR signalling. Oncogene 19:3021–3031. doi:10.1038/sj.onc.1203622 CrossRef PubMed
51.Dhar R, Persaud SD, Mireles JR, Basu A (2009) Proteolytic cleavage of p70 ribosomal S6 kinase by caspase-3 during DNA damage-induced apoptosis. Biochemistry 48:1474–1480. doi:10.1021/bi801840s CrossRef PubMed PubMedCentral - 作者单位：Kyung Hwan Jegal (1)
Hae Li Ko (1)
Sang Mi Park (1)
Sung Hui Byun (1)
Keon Wook Kang (2)
Il Je Cho (1)
Sang Chan Kim (1)
1. Department of Herbal Formulation, MRC-GHF, College of Korean Medicine, Daegu Haany University, Gyeongsan, Gyeongsangbuk-do, 38610, Republic of Korea
2. College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul, 08826, Republic of Korea - 刊物类别：Medicine
- 刊物主题：Medicine & Public Health
Oncology
Cancer Research
Cell Biology
Biochemistry
Virology - 出版者：Springer Netherlands
- ISSN：1573-675X
文摘
Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) has many pharmacological activities including anti-inflammation, anti-oxidant and anti-cancer effects. Autophagy is the basic cellular machinery involving the digestion of damaged cellular components. In the present study, we investigated the protection effects of eupatilin against arachidonic acid (AA) and iron-induced oxidative stress in HepG2 cells and tried to elucidate the molecular mechanisms responsible. Eupatilin increased cell viability against AA + iron in a concentration-dependent manner and prevented mitochondrial dysfunction and reactive oxygen species (ROS) production. In addition, AA + iron increased the levels of pro-apoptotic proteins and these changes were prevented by eupatilin. Eupatilin also induced autophagy, as evidenced by the accumulation of microtubule-associated protein 1 light chain3-II and the detection of autophagic vacuoles. Furthermore, the protective effects of eupatilin on mitochondrial dysfunction and ROS production were significantly abolished by autophagy inhibitors. Eupatilin also increased the mRNA level of sestrin-2 and its promoter-driven reporter gene activity, which resulted in the up-regulation of sestrin-2 protein. Finally, gene silencing using sestrin-2 siRNA and the ectopic expression of recombinant adenoviral sestrin-2 indicated that sestrin-2 induction by eupatilin was required for autophagy-mediated cytoprotection against AA + iron. Our results suggest that eupatilin activates sestrin-2-dependent autophagy, thereby preventing oxidative stress induced by AA + iron.