JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2014, Vol. 52 ›› Issue (9): 20-25.doi: 10.6040/j.issn.1671-7554.0.2014.203

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Juices of cherry and strawberry confer protection of human bronchial epithelial cells against arsenic-induced toxicity via activation of Nrf2 signaling pathway

KONG Degang1, WANG Lili2, ZHOU Honglei1, REN Dongmei3, LOU Hongxiang3, SHEN Tao3   

  1. 1. School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong, China;
    2. Division 1, Department of Paediatrics, Peopel's Hospital of Rizhao, Rizhao 276800, Shandong, China;
    3. Key Lab of Chemical Biology Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong, China
  • Received:2014-04-08 Revised:2014-09-05 Online:2014-09-10 Published:2014-09-10
  • Contact: 沈涛。E-mail:shentao@sdu.edu.cn E-mail:shentao@sdu.edu.cn

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Abstract: Objective To investigate the effects of cherry and strawberry juices on NF-E2-related factor 2(Nrf2) signaling pathway, and to evaluate their protection effects on arsenic-induced toxicity in human bronchial epithelial (HBE) cells. Methods Human breast cancer 231 cells were randomly divided into the control group, sulforaphen treated group, and juice treated groups (juice dilution ratios were 1:10,1:20,1:40 and 1:80, respectively), and then antioxidant response element(ARE) luciferase reporter gene assay and Western blotting analysis were adopted for screening and identification of juice on Nrf2 signaling pathway; HBE cells were randomly divided into the control group, sul-foraphen treated group, and juice treated groups (juice dilution ratios were 1:10,1:20, and 1:40, respectively), and then the QuantiChrom glutathione (GSH) assay kit were used to detect the intracellular GSH levels; MTT assay and cell transfection were carried out to evaluate their protection effects against arsenic-induced toxicity in HBE cells. Results Juices of cherry and strawberry increased the luciferase activity in a dose-dependent manner, enhanced the protein expression of Nrf2 and its downstream genes NADPH:quinone oxidoreduefase Ⅰ(NQO1) and gamma glutamyl cysteine synthetase (γGCS) in MDA-MB-231 cells, and up-regulated the intracellular GSH levels in HBE cells. Co-treatment with juice and arsenic evidently improved HBE cell survival in response to arsenic treatment alone, while the juices no longer protected the HBE cells whose Nrf2 expression was koncked down by Nrf2-siRNA. Conclusion Juices of cherry and strawberry confer the protection effects on HBE cells against arsenic-induced toxicity in a Nrf2-dependent manner.

Key words: Nrf2 signaling pathway, Cherry, Strawberry, Arsenic, Human bronchial epithelial cells

CLC Number: 

  • R966
[1] Moi P, Chan K, Asunis I, et al. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region[J]. Proc Natl Acad Sci U S A, 1994, 91(21):9926-9930.
[2] Rushmore T H, Morton M R, Pickett C B. The antioxidant responsive element. activation by oxidative stress and identification of the DNA consensus sequence required for functional activity[J]. J Biol Chem, 1991, 266(18):11632-11639.
[3] 蔡维霞, 张军, 胡大海. 氧化和化学应激的防御性转导通路-Nrf2/ARE[J]. 中国生物化学和分子生物学报, 2009, 25(4):297-303. CAI Weixia, ZHANG Jun, HU Dahai. Defensive pathway of Nrf2/ARE involved in oxidative and chemical stress[J]. Chin J Biochem Mol Biol, 2009, 25(4):297-303.
[4] Moinova H R, Mulcahy R T. Up-regulation of the human γ-glutamylcysteine synthetase regulatory subunit gene involves binding of Nrf-2 to an electrophile responsive element[J]. Biochem Biophys Res Commun, 1999, 261(3):661-668.
[5] Itoh K, Chiba T, Takahashi S, et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements[J]. Biochem Biophys Res Commun, 1997, 236(2):313-322.
[6] Vollrath V, Wielandt A, Iruretagoyena M, et al. Role of Nrf2 in the regulation of the Mrp2 (ABCC2) gene[J]. Biochem J, 2006, 395(3):599-609.
[7] Copple I M. The Keap1-Nrf2 cell defense pathway—a promising therapeutic target?[J]. Adv Pharmacol, 2012, 63:43-79.
[8] Magesh S, Chen Y, Hu L. Small molecule modulators of Keap1-Nrf2-ARE pathway as potential preventive and therapeutic agents[J]. Med Res Rev, 2012, 32(4):687-726.
[9] Cho H Y, Kleeberger S R. Nrf2 protects against airway disorders[J]. Toxicol Appl Pharm, 2010, 244(1):43-56.
[10] 王秀君, 李欣, 唐修文. Nrf2通路在肿瘤化学预防中的研究进展[J]. 化学进展, 2013, 25(9):1544-1552. WANG Xiujun, LI Xin, TANG Xiuwen. The role of Nrf2 in carcinogenesis[J]. Progress in Chemistry, 2013, 25(9):1544-1552.
[11] Sussan T E, Rangasamy T, Blake D J, et al. Targeting Nrf2 with the triterpenoid CDDO-imidazolide attenuates cigarette smoke-induced emphysema and cardiac dysfunction in mice[J]. Proc Natl Acad Sci U S A, 2009, 106(1):250-255.
[12] Iizuka T, Ishii Y, Itoh K, et al. Nrf2-deficient mice are highly susceptible to cigarette smoke-induced emphysema[J]. Genes to Cells, 2005, 10(12):1113-1125.
[13] Blake D J, Singh A, Kombairaju P, et al. Deletion of Keap1 in the lung attenuates acute cigarette smoke-induced oxidative stress and inflammation[J]. Am J Respir Cell Mol Biol, 2010, 42(5):524.
[14] Zheng Y, Tao S, Lian F, et al. Sulforaphane prevents pulmonary damage in response to inhaled arsenic by activating the Nrf2-defense response[J]. Toxicol Appl Pharm, 2012, 265(3):292-299.
[15] Kou X, Kirberger M, Yang Y, et al. Natural products for cancer prevention associated with Nrf2-ARE pathway[J]. Food Science and Human Wellness, 2013, 2(1):22-28.
[16] Dickinson D A, Forman H J. Cellular glutathione and thiols metabolism[J]. Biochem Pharmacol, 2002, 64(5):1019-1026.
[17] Circu M L, Aw T Y. Reactive oxygen species, cellular redox systems, and apoptosis[J]. Free Radical Bio Med, 2010, 48(6):749-762.
[18] Barchowsky A, Klei L R, Dudek E J, et al. Stimulation of reactive oxygen, but not reactive nitrogen species, in vascular endothelial cells exposed to low levels of arsenite[J]. Free Radical Bio Med, 1999, 27(11):1405-1412.
[19] Barchowsky A, Dudek E J, Treadwell M D, et al. Arsenic induces oxidant stress and NF-kB activation in cultured aortic endothelial cells[J]. Free Radical Bio Med, 1996, 21(6):783-790.
[20] Shi H, Shi X, Liu K J. Oxidative mechanism of arsenic toxicity and carcinogenesis[J]. Mol Cell Biochem, 2004, 255(1/2):67-78.
[21] Tao S, Zheng Y, Lau A, et al. Tanshinone I activates the Nrf2-dependent antioxidant response and protects against As (Ⅲ)-induced lung inflammation in vitro and in vivo[J]. Antioxid Redox Signal, 2013, 19(14):1647-1661.
[22] Jiang T, Huang Z, Chan J Y, et al. Nrf2 protects against As (Ⅲ)-induced damage in mouse liver and bladder[J]. Toxicol Appl Pharm, 2009, 240(1):8-14.
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