Molecular Nutrition

Role of Kelch-Like Epichlorohydrin-Associated Protein 1-Nuclear Factor-E2-Related Factor 2-Antioxidant Response Element Signaling Pathway in Anti-Oxidative Stress and Its Regulators

Expand
  • 1. Animal Nutrition and Feed Institute, Agricultural and Animal Husbandry Academy of Inner Mongolia, Hohhot 010031, China;
    2. College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China

Received date: 2016-10-13

  Online published: 2017-04-14

Abstract

Kelch-like epichlorohydrin-associated protein 1-nuclear factor-E2-related factor 2-antioxidant response element (Keap1-Nrf2-ARE) signaling pathway is one of the most important cellular defense mechanisms against oxidative stress and xenobiotic damage, and it is closely associated with inflammatory diseases, including cancer, neurodegenerative diseases, cardiovascular diseases, aging and so on. Activation of Nrf2 signaling induces the transcriptional regulation of ARE-dependent expression of various detoxifying and antioxidant defense enzymes and proteins. Keap1-Nrf2-ARE signaling pathway has become an attractive target for the prevention and treatment of oxidative stress-related diseases and inflammatory diseases. Oxidative stress, the role of Keap1-Nrf2-ARE signaling pathway in anti-oxidative stress and the regulators of Keap1-Nrf2-ARE signaling pathway were reviewed in this paper.

Cite this article

MA Yanfen, WU Zhihong, ZHAO Lei, GAO Min . Role of Kelch-Like Epichlorohydrin-Associated Protein 1-Nuclear Factor-E2-Related Factor 2-Antioxidant Response Element Signaling Pathway in Anti-Oxidative Stress and Its Regulators[J]. Chinese Journal of Animal Nutrition, 2017 , 29(4) : 1091 -1095 . DOI: 10.3969/j.issn.1006-267x.2017.04.001

References

[1] LYAKHOVICH V V,VAVILIN V A,ZENKOV N K,et al.Active defense under oxidative stress.The antioxidant responsive element[J].Biochemistry,2006,71(9):962-974.

[2] DINKOVA-KOSTOVA A T,TALALAY P.Direct and indirect antioxidant properties of inducers of cytoprotective proteins[J].Molecular Nutrition & Food Research,2008,52(Suppl.1):S128-S138.

[3] HOLTZCLAW W D,DINKOVA-KOSTOVA A T,TALALAY P.Protection against electrophile and oxidative stress by induction of phase 2 genes:the quest for the elusive sensor that responds to inducers[J].Advances in Enzyme Regulation,2004,44(1):335-367.  

[4] STEWART J D,HENGSTLER J G,BOLT H M.Control of oxidative stress by the Keap1-Nrf2 pathway[J].Archives of Toxicology,2011,85:239.

[5] TAGUCHI K,MOTOHASHI H,YAMAMOTO M.Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution[J].Genes to Cells,2011,16(2):123-140.  

[6] 马燕芬,宋利文,高民,等.氧化应激对围产期奶牛乳房炎的影响及其调控机制[J].动物营养学报,2015,27(3):671-676.

[7] SURH Y J,KUNDU J K,NA H K.Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals[J].Planta Medica,2008,74(13):1526-1539.  

[8] KUNDU J K,SURH Y J.Inflammation:gearing the journey to cancer[J].Mutation Research/Reviews in Mutation Research,2008,659(1/2):15-30.

[9] MA Q.Transcriptional responses to oxidative stress:pathological and toxicological implications[J].Pharmacology & Therapeutics,2010,125(3):376-393.  

[10] COPPLE I M.The Keap1-Nrf2 cell defense pathway-a promising therapeutic target?[J].Advances in Pharmacology,2012,63:43-79.

[11] MAGESH S,CHEN Y,HU L Q.Small molecule modulators of Keap1-Nrf2-ARE pathway as potential preventive and therapeutic agents[J].Medicinal Research Reviews,2012,32(4):687-726.  

[12] CHO H Y,REDDY S P,KLEEBERGER S R.Nrf2 defends the lung from oxidative stress[J].Antioxidants & Redox Signaling,2006,8(1/2):76-87.

[13] KEUM Y S,JEONG W S,KONG A N T.Chemoprevention by isothiocyanates and their underlying molecular signaling mechanisms[J].Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis,2004,555(1/2):191-202.

[14] KEUM Y S.Regulation of Nrf2-mediated phase Ⅱ detoxification and anti-oxidant genes[J].Biomolecules and Therapeutics (Seoul),2012,20(2):144-151.  

[15] NITURE S K,JAIN A K,JAISWAL A K.Antioxidant-induced modification of INrf2 cysteine 151 and PKC-δ-mediated phosphorylation of Nrf2 serine 40 are both required for stabilization and nuclear translocation of Nrf2 and increased drug resistance[J].Journal of Cell Science,2009,122(24):4452-4464.  

[16] JAIN A K,JAISWAL A K.Phosphorylation of tyrosine 568 controls nuclear export of Nrf2[J].The Journal of Biological Chemistry,2006,281(17):12132-12142.  

[17] LIBY K T,SPORN M B.Synthetic oleanane triterpenoids:multifunctional drugs with a broad range of applications for prevention and treatment of chronic disease[J].Pharmacological Reviews,2012,64(4):972-1003.  

[18] SCANNEVIN R H,CHOLLATE S,JUNG M Y,et al.Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the nuclear factor (erythroid-derived 2)-like 2 pathway[J].The Journal of Pharmacology and Experimental Therapeutics,2012,341(1):274-284.  

[19] 杨光照.EGCG通过上调Nrf2/HO-1途径降低PM2.5所致HUVEC氧化损伤的机制研究[D].博士学位论文.太原:山西医科大学,2015.

[20] FAROMBI E O,SHROTRIYA S,NA H K,et al.Curcumin attenuates dimethylnitrosamine-induced liver injury in rats through Nrf2-mediated induction of heme oxygenase-1[J].Food and Chemical Toxicology,2008,46(4):1279-1287.  

[21] ZHONG J L,EDWARDS G P,RAVAL C,et al.The role of Nrf2 in ultraviolet a mediated heme oxygenase 1 induction in human skin fibroblasts[J].Photochemical & Photobiological Science,2010,9(1):18-24.  

[22] OKOUCHI M,OKAYAMA N,ALEXANDER J S,et al.NRF2-dependent glutamate-L-cysteine ligase catalytic subunit expression mediates insulin protection against hyperglycemia-induced brain endothelial cell apoptosis[J].Current Neurovascular Research,2006,3(4):249-261.  

[23] 蒋怡芳.白藜芦醇对过氧化氢诱导的原代脊髓星形胶质细胞毒性的保护作用[D].硕士学位论文.石家庄:河北医科大学,2009.

[24] 鲍兵.莱菔硫烷激活Nrf2-ARE通路拮抗PC12细胞氧化应激损伤的机制研究[D].硕士学位论文.南昌:南昌大学,2013.

[25] WANG X J,HAYES J D,HENDERSON C J,et al.Identification of retinoic acid as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha[J].Proceedings of the National Academy of Sciences of the United States of America,2007,104(49):19589-19594.  

[26] TANG X W,WANG H Y,FAN L F,et al.Luteolin inhibits Nrf2 leading to negative regulation of the Nrf2/ARE pathway and sensitization of human lung carcinoma A549 cells to therapeutic drugs[J].Free Radical Biology and Medicine,2011,50(11):1599-1609.  

[27] OHNUMA T,MATSUMOTO T,ITOI A,et al.Enhanced sensitivity of A549 cells to the cytotoxic action of anticancer drugs via suppression of Nrf2 by procyanidins from cinnamomi cortex extract[J].Biochemical and Biophysical Research Communications,2011,413(4):623-629.  

[28] GAO A M,KE Z P,WANG J N,et al.Apigenin sensitizes doxorubicin-resistant hepatocellular carcinoma BEL-7402/ADM cells to doxorubicin via inhibiting PI3K/Akt/Nrf2 pathway[J].Carcinogenesis,2013,34(8):1806-1814.  

[29] GAO A M,KE Z P,SHI F,et al.Chrysin enhances sensitivity of BEL-7402/ADM cells to doxorubicin by suppressing PI3K/Akt/Nrf2 and ERK/Nrf2 pathway[J].Chemico-Biological Interactions,2013,206(1):100-108.  
Outlines

/