Skip to main content
Log in

Protective effects of bovine milk exosomes against oxidative stress in IEC-6 cells

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

Bovine milk exosomes, which are enriched with microRNAs (miRNAs) and proteins, regulate immune response and growth. In the present study, we aimed to assess the protective effects of bovine milk exosomes against oxidative stress of intestinal crypt epithelial cells (IEC-6).

Methods

Bovine milk exosomes were isolated and characterized. To assess the protective effects of exosomes, IEC-6 cells were pretreated with exosomes, followed by H2O2. Cell viability and levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GPX), reactive oxidative species (ROS), and lactate dehydrogenase (LDH) were measured. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (Ho1) genes, and miR-146a, miR-155, and the HO-1 protein were also determined.

Results

The isolated bovine milk exosome were positive for CD63 and CD9 expression. The exosomes were approximately circular and had a diameter of about 67.23 nm. Pretreatment of IEC-6 cells with bovine milk exosomes enhanced cell viability; increased SOD and GPX activities; and reduced LDH, ROS, and MDA levels after H2O2 challenge. Further analysis showed that exosome pretreatment increased intracellular miR-146a and miR-155 levels. Exosome pretreatment inhibited the elevation of Nrf2 and Ho1 gene expression induced by H2O2, but promoted HO-1 protein expression.

Conclusion

The results indicated that bovine milk exosomes exerted protective effects against oxidative stress in IEC-6 cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE (2014) Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev 94(2):329–354. https://doi.org/10.1152/physrev.00040.2012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Aviello G, Knaus UG (2017) ROS in gastrointestinal inflammation: Rescue Or Sabotage? Br J Pharmacol 174(12):1704–1718. https://doi.org/10.1111/bph.13428

    Article  CAS  PubMed  Google Scholar 

  3. Peng YC, Hsu CL, Tung CF, Chou WK, Huang LR, Hung DZ, Hu WH, Yang DY (2008) Chemiluminescence assay of mucosal reactive oxygen species in gastric cancer, ulcer and antral mucosa. Hepatogastroenterology 55(82–83):770–773

    CAS  PubMed  Google Scholar 

  4. Grisham MB (1994) Oxidants and free radicals in inflammatory bowel disease. Lancet 344(8926):859–861

    Article  CAS  PubMed  Google Scholar 

  5. Pavlick KP, Laroux FS, Fuseler J, Wolf RE, Gray L, Hoffman J, Grisham MB (2002) Role of reactive metabolites of oxygen and nitrogen in inflammatory bowel disease. Free Radic Biol Med 33(3):311–322

    Article  CAS  PubMed  Google Scholar 

  6. Tian T, Wang Z, Zhang J (2017) Pathomechanisms of oxidative stress in inflammatory bowel disease and potential antioxidant therapies. Oxid Med Cell Longev 2017:4535194. https://doi.org/10.1155/2017/4535194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kekec Y, Paydas S, Tuli A, Zorludemir S, Sakman G, Seydaoglu G (2009) Antioxidant enzyme levels in cases with gastrointesinal cancer. Eur J Intern Med 20(4):403–406. https://doi.org/10.1016/j.ejim.2008.12.003

    Article  CAS  PubMed  Google Scholar 

  8. Inokuma T, Haraguchi M, Fujita F, Tajima Y, Kanematsu T (2009) Oxidative stress and tumor progression in colorectal cancer. Hepatogastroenterology 56(90):343–347

    CAS  PubMed  Google Scholar 

  9. Haug A, Hostmark AT, Harstad OM (2007) Bovine milk in human nutrition—a review. Lipids Health Dis 6:25. https://doi.org/10.1186/1476-511x-6-25

    Article  PubMed  PubMed Central  Google Scholar 

  10. Arntz OJ, Pieters BC, Oliveira MC, Broeren MG, Bennink MB, de Vries M, van Lent PL, Koenders MI, van den Berg WB, van der Kraan PM, van de Loo FA (2015) Oral administration of bovine milk derived extracellular vesicles attenuates arthritis in two mouse models. Mol Nutr Food Res 59(9):1701–1712. https://doi.org/10.1002/mnfr.201500222

    Article  CAS  PubMed  Google Scholar 

  11. Mansson HL (2008) Fatty acids in bovine milk fat. Food Nutr Res https://doi.org/10.3402/fnr.v52i0.1821

    Article  PubMed  PubMed Central  Google Scholar 

  12. Admyre C, Johansson SM, Qazi KR, Filen JJ, Lahesmaa R, Norman M, Neve EP, Scheynius A, Gabrielsson S (2007) Exosomes with immune modulatory features are present in human breast milk. J Immunol 179(3):1969–1978

    Article  CAS  PubMed  Google Scholar 

  13. Hata T, Murakami K, Nakatani H, Yamamoto Y, Matsuda T, Aoki N (2010) Isolation of bovine milk-derived microvesicles carrying mRNAs and microRNAs. Biochem Biophys Res Commun 396(2):528–533. https://doi.org/10.1016/j.bbrc.2010.04.135

    Article  CAS  PubMed  Google Scholar 

  14. Thery C, Zitvogel L, Amigorena S (2002) Exosomes: composition, biogenesis and function. Nat Rev Immunol 2(8):569–579. https://doi.org/10.1038/nri855

    Article  CAS  PubMed  Google Scholar 

  15. Raposo G, Stoorvogel W (2013) Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200(4):373–383. https://doi.org/10.1083/jcb.201211138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Huang X, Yuan T, Tschannen M, Sun Z, Jacob H, Du M, Liang M, Dittmar RL, Liu Y, Liang M, Kohli M, Thibodeau SN, Boardman L, Wang L (2013) Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genom 14:319. https://doi.org/10.1186/1471-2164-14-319

    Article  CAS  Google Scholar 

  17. Izumi H, Tsuda M, Sato Y, Kosaka N, Ochiya T, Iwamoto H, Namba K, Takeda Y (2015) Bovine milk exosomes contain microRNA and mRNA and are taken up by human macrophages. J Dairy Sci 98(5):2920–2933. https://doi.org/10.3168/jds.2014-9076

    Article  CAS  PubMed  Google Scholar 

  18. Abels ER, Breakefield XO (2016) Introduction to extracellular vesicles: biogenesis, rna cargo selection, content, release, and uptake. Cell Mol Neurobiol 36(3):301–312. https://doi.org/10.1007/s10571-016-0366-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Freedman JE, Gerstein M, Mick E, Rozowsky J, Levy D, Kitchen R, Das S, Shah R, Danielson K, Beaulieu L, Navarro FC, Wang Y, Galeev TR, Holman A, Kwong RY, Murthy V, Tanriverdi SE, Koupenova-Zamor M, Mikhalev E, Tanriverdi K (2016) Diverse human extracellular RNAs are widely detected in human plasma. Nat Commun 7:11106. https://doi.org/10.1038/ncomms11106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Greening DW, Gopal SK, Xu R, Simpson RJ, Chen W (2015) Exosomes and their roles in immune regulation and cancer. Semin Cell Dev Biol 40:72–81. https://doi.org/10.1016/j.semcdb.2015.02.009

    Article  CAS  PubMed  Google Scholar 

  21. Gangoda L, Boukouris S, Liem M, Kalra H, Mathivanan S (2015) Extracellular vesicles including exosomes are mediators of signal transduction: are they protective or pathogenic? Proteomics 15(2–3):260–271. https://doi.org/10.1002/pmic.201400234

    Article  CAS  PubMed  Google Scholar 

  22. Mittelbrunn M, Gutierrez-Vazquez C, Villarroya-Beltri C, Gonzalez S, Sanchez-Cabo F, Gonzalez MA, Bernad A, Sanchez-Madrid F (2011) Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun 2:282. https://doi.org/10.1038/ncomms1285

    Article  CAS  PubMed  Google Scholar 

  23. Yanez-Mo M, Siljander PR, Andreu Z, Zavec AB, Borras FE, Buzas EI, Buzas K, Casal E, Cappello F, Carvalho J, Colas E, Cordeiro-da Silva A, Fais S, Falcon-Perez JM, Ghobrial IM, Giebel B, Gimona M, Graner M, Gursel I, Gursel M, Heegaard NH, Hendrix A, Kierulf P, Kokubun K, Kosanovic M, Kralj-Iglic V, Kramer-Albers EM, Laitinen S, Lasser C, Lener T, Ligeti E, Line A, Lipps G, Llorente A, Lotvall J, Mancek-Keber M, Marcilla A, Mittelbrunn M, Nazarenko I, Nolte-'t Hoen EN, Nyman TA, O'Driscoll L, Olivan M, Oliveira C, Pallinger E, Del Portillo HA, Reventos J, Rigau M, Rohde E, Sammar M, Sanchez-Madrid F, Santarem N, Schallmoser K, Ostenfeld MS, Stoorvogel W, Stukelj R, Van der Grein SG, Vasconcelos MH, Wauben MH, De Wever O (2015) Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles 4:27066. https://doi.org/10.3402/jev.v4.27066

    Article  PubMed  Google Scholar 

  24. Yamashita T, Takahashi Y, Takakura Y (2018) Possibility of exosome-based therapeutics and challenges in production of exosomes eligible for therapeutic application. Biol Pharm Bull 41(6):835–842. https://doi.org/10.1248/bpb.b18-00133

    Article  CAS  PubMed  Google Scholar 

  25. Melnik BC, John SM, Schmitz G (2014) Milk: an exosomal microRNA transmitter promoting thymic regulatory T cell maturation preventing the development of atopy? J Transl Med 12:43. https://doi.org/10.1186/1479-5876-12-43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Nordgren TM, Heires AJ, Zempleni J, Swanson BJ, Wichman C, Romberger DJ (2019) Bovine milk-derived extracellular vesicles enhance inflammation and promote M1 polarization following agricultural dust exposure in mice. J Nutr Biochem 64:110–120. https://doi.org/10.1016/j.jnutbio.2018.10.017

    Article  CAS  PubMed  Google Scholar 

  27. Munir J, Lee M, Ryu S (2019) Exosomes in food: health benefits and clinical relevance in diseases. Adv Nutr. https://doi.org/10.1093/advances/nmz123

    Article  PubMed Central  Google Scholar 

  28. Zhou F, Paz HA, Sadri M, Cui J, Kachman SD, Fernando SC, Zempleni J (2019) Dietary bovine milk exosomes elicit changes in bacterial communities in C57BL/6 mice. Am J Physiol Gastrointest Liver Physiol 317(5):G618–G624. https://doi.org/10.1152/ajpgi.00160.2019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Li B, Hock A, Wu RY, Minich A, Botts SR, Lee C, Antounians L, Miyake H, Koike Y, Chen Y, Zani A, Sherman PM, Pierro A (2019) Bovine milk-derived exosomes enhance goblet cell activity and prevent the development of experimental necrotizing enterocolitis. PLoS ONE 14(1):e0211431. https://doi.org/10.1371/journal.pone.0211431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Martin C, Patel M, Williams S, Arora H, Sims B (2018) Human breast milk-derived exosomes attenuate cell death in intestinal epithelial cells. Innate Immun 24(5):278–284. https://doi.org/10.1177/1753425918785715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Chen T, Xie MY, Sun JJ, Ye RS, Cheng X, Sun RP, Wei LM, Li M, Lin DL, Jiang QY, Xi QY, Zhang YL (2016) Porcine milk-derived exosomes promote proliferation of intestinal epithelial cells. Sci Rep 6:33862. https://doi.org/10.1038/srep33862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Yu S, Zhao Z, Sun L, Li P (2017) Fermentation results in quantitative changes in milk-derived exosomes and different effects on cell growth and survival. J Agric Food Chem 65(6):1220–1228. https://doi.org/10.1021/acs.jafc.6b05002

    Article  CAS  PubMed  Google Scholar 

  33. Leiferman A, Shu J, Grove R, Cui J, Adamec J, Zempleni J (2018) A diet defined by its content of bovine milk exosomes and their RNA cargos has moderate effects on gene expression, amino acid profiles and grip strength in skeletal muscle in C57BL/6 mice. J Nutr Biochem 59:123–128. https://doi.org/10.1016/j.jnutbio.2018.06.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Mutai E, Zhou F, Zempleni J (2017) Depletion of dietary bovine milk exosomes impairs sensorimotor gating and spatial learning in C57BL/6 Mice. FASEB J 31(1_supplement):150.154–150.154. https://doi.org/10.1096/fasebj.31.1_supplement.150.4

    Article  Google Scholar 

  35. Aguilar-Lozano A, Baier S, Grove R, Shu J, Giraud D, Leiferman A, Mercer KE, Cui J, Badger TM, Adamec J, Andres A, Zempleni J (2018) Concentrations of purine metabolites are elevated in fluids from adults and infants and in livers from mice fed diets depleted of bovine milk exosomes and their RNA cargos. J Nutr 148(12):1886–1894. https://doi.org/10.1093/jn/nxy223

    Article  PubMed  PubMed Central  Google Scholar 

  36. Sadri M, Xie F, Wood J, Zempleni J (2016) Dietary depletion of cow’s Milk microRNAs impairs fecundity in mice. FASEB J 30(1_supplement):673.675–673.675. https://doi.org/10.1096/fasebj.30.1_supplement.673.5

    Article  Google Scholar 

  37. Zempleni J, Sukreet S, Zhou F, Wu D, Mutai E (2019) Milk-Derived Exosomes and metabolic regulation. Annu Rev Anim Biosci 7:245–262. https://doi.org/10.1146/annurev-animal-020518-115300

    Article  CAS  PubMed  Google Scholar 

  38. Kusuma RJ, Manca S, Friemel T, Sukreet S, Nguyen C, Zempleni J (2016) Human vascular endothelial cells transport foreign exosomes from cow's milk by endocytosis. Am J Physiol Cell Physiol:ajpcell 00169:02015. https://doi.org/10.1152/ajpcell.00169.2015

    Article  Google Scholar 

  39. Jo HS, Kim DS, Ahn EH, Kim DW, Shin MJ, Cho SB, Park JH, Lee CH, Yeo EJ, Choi YJ, Yeo HJ, Chung CS, Cho SW, Han KH, Park J, Eum WS, Choi SY (2016) Protective effects of Tat-NQO1 against oxidative stress-induced HT-22 cell damage, and ischemic injury in animals. BMB Rep 49(11):617–622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhang J, Cai S, Li J, Xiong L, Tian L, Liu J, Huang J, Liu Z (2016) Neuroprotective effects of theaflavins against oxidative stress-induced apoptosis in PC12 cells. Neurochem Res 41(12):3364–3372. https://doi.org/10.1007/s11064-016-2069-8

    Article  CAS  PubMed  Google Scholar 

  41. Bhatti FU, Mehmood A, Latief N, Zahra S, Cho H, Khan SN, Riazuddin S (2017) Vitamin E protects rat mesenchymal stem cells against hydrogen peroxide-induced oxidative stress in vitro and improves their therapeutic potential in surgically-induced rat model of osteoarthritis. Osteoarthr Cartil 25(2):321–331. https://doi.org/10.1016/j.joca.2016.09.014

    Article  CAS  Google Scholar 

  42. Bettaib J, Talarmin H, Kalai FZ, Giroux-Metges MA, Ksouri R (2017) Limoniastrum guyonianum prevents H2O2-induced oxidative damage in IEC-6 cells by enhancing enzyamtic defense, reducing glutathione depletion and JNK phosphorylation. Biomed Pharmacother 95:1404–1411. https://doi.org/10.1016/j.biopha.2017.09.068

    Article  CAS  PubMed  Google Scholar 

  43. Zou L, Sato N, Kone BC (2004) Alpha-melanocyte stimulating hormone protects against H2O2-induced inhibition of wound restitution in IEC-6 cells via a Syk kinase- and NF-kappabeta-dependent mechanism. Shock 22(5):453–459

    Article  CAS  PubMed  Google Scholar 

  44. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(T)(-Delta Delta C) method. Methods 25(4):402–408. https://doi.org/10.1006/meth.2001.1262

    Article  CAS  PubMed  Google Scholar 

  45. Zhou Y, Xu H, Xu W, Wang B, Wu H, Tao Y, Zhang B, Wang M, Mao F, Yan Y, Gao S, Gu H, Zhu W, Qian H (2013) Exosomes released by human umbilical cord mesenchymal stem cells protect against cisplatin-induced renal oxidative stress and apoptosis in vivo and in vitro. Stem Cell Res Ther 4(2):34. https://doi.org/10.1186/scrt194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Tan CY, Lai RC, Wong W, Dan YY, Lim SK, Ho HK (2014) Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models. Stem Cell Res Ther 5(3):76. https://doi.org/10.1186/scrt465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. de Godoy MA, Saraiva LM, de Carvalho LRP, Vasconcelos-Dos-Santos A, Beiral HJV, Ramos AB, Silva LRP, Leal RB, Monteiro VHS, Braga CV, de Araujo-Silva CA, Sinis LC, Bodart-Santos V, Kasai-Brunswick TH, Alcantara CL, Lima A, da Cunha ESNL, Galina A, Vieyra A, De Felice FG, Mendez-Otero R, Ferreira ST (2018) Mesenchymal stem cells and cell-derived extracellular vesicles protect hippocampal neurons from oxidative stress and synapse damage induced by amyloid-beta oligomers. J Biol Chem 293(6):1957–1975. https://doi.org/10.1074/jbc.M117.807180

    Article  PubMed  Google Scholar 

  48. Arslan F, Lai RC, Smeets MB, Akeroyd L, Choo A, Aguor EN, Timmers L, van Rijen HV, Doevendans PA, Pasterkamp G, Lim SK, de Kleijn DP (2013) Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Res 10(3):301–312. https://doi.org/10.1016/j.scr.2013.01.002

    Article  CAS  PubMed  Google Scholar 

  49. Badawy AA, El-Magd MA, AlSadrah SA (2018) Therapeutic effect of camel milk and its exosomes on MCF7 cells in vitro and in vivo. Integr Cancer Ther 17(4):1235–1246. https://doi.org/10.1177/1534735418786000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Shoji H, Oguchi S, Shinohara K, Shimizu T, Yamashiro Y (2007) Effects of iron-unsaturated human lactoferrin on hydrogen peroxide-induced oxidative damage in intestinal epithelial cells. Pediatr Res 61(1):89–92. https://doi.org/10.1203/01.pdr.0000250198.22735.20

    Article  PubMed  Google Scholar 

  51. Kensler TW, Wakabayashi N, Biswal S (2007) Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol 47:89–116. https://doi.org/10.1146/annurev.pharmtox.46.120604.141046

    Article  CAS  PubMed  Google Scholar 

  52. Sun W, Julie Li YS, Huang HD, Shyy JY, Chien S (2010) microRNA: a master regulator of cellular processes for bioengineering systems. Annu Rev Biomed Eng 12:1–27. https://doi.org/10.1146/annurev-bioeng-070909-105314

    Article  CAS  PubMed  Google Scholar 

  53. Catalanotto C, Cogoni C, Zardo G (2016) MicroRNA in control of gene expression: an overview of nuclear functions. Int J Mol Sci. https://doi.org/10.3390/ijms17101712

    Article  PubMed  PubMed Central  Google Scholar 

  54. Vidigal JA, Ventura A (2015) The biological functions of miRNAs: lessons from in vivo studies. Trends Cell Biol 25(3):137–147. https://doi.org/10.1016/j.tcb.2014.11.004

    Article  CAS  PubMed  Google Scholar 

  55. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233. https://doi.org/10.1016/j.cell.2009.01.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Wan G, Liu Y, Han C, Zhang X, Lu X (2014) Noncoding RNAs in DNA repair and genome integrity. Antioxid Redox Signal 20(4):655–677. https://doi.org/10.1089/ars.2013.5514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Bu H, Wedel S, Cavinato M, Jansen-Durr P (2017) MicroRNA regulation of oxidative stress-induced cellular senescence. Oxid Med Cell Longev 2017:2398696. https://doi.org/10.1155/2017/2398696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Espinosa-Diez C, Miguel V, Mennerich D, Kietzmann T, Sanchez-Perez P, Cadenas S, Lamas S (2015) Antioxidant responses and cellular adjustments to oxidative stress. Redox Biol 6:183–197. https://doi.org/10.1016/j.redox.2015.07.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Paladino S, Conte A, Caggiano R, Pierantoni GM, Faraonio R (2018) Nrf2 pathway in age-related neurological disorders: insights into MicroRNAs. Cell Physiol Biochem 47(5):1951–1976. https://doi.org/10.1159/000491465

    Article  CAS  PubMed  Google Scholar 

  60. Xie Y, Chen Y (2016) microRNAs: emerging targets regulating oxidative stress in the models of Parkinson's disease. Front Neurosci 10:298. https://doi.org/10.3389/fnins.2016.00298

    Article  PubMed  PubMed Central  Google Scholar 

  61. Matouskova P, Hanouskova B, Skalova L (2018) MicroRNAs as potential regulators of glutathione peroxidases expression and their role in obesity and related pathologies. Int J Mol Sci. https://doi.org/10.3390/ijms19041199

    Article  PubMed  PubMed Central  Google Scholar 

  62. Gong YY, Luo JY, Wang L, Huang Y (2018) MicroRNAs regulating reactive oxygen species in cardiovascular diseases. Antioxid Redox Signal 29(11):1092–1107. https://doi.org/10.1089/ars.2017.7328

    Article  CAS  PubMed  Google Scholar 

  63. Izumi H, Kosaka N, Shimizu T, Sekine K, Ochiya T, Takase M (2012) Bovine milk contains microRNA and messenger RNA that are stable under degradative conditions. J Dairy Sci 95(9):4831–4841. https://doi.org/10.3168/jds.2012-5489

    Article  CAS  PubMed  Google Scholar 

  64. Izumi H, Kosaka N, Shimizu T, Sekine K, Ochiya T, Takase M (2013) Purification of RNA from milk whey. Methods Mol Biol 1024:191–201. https://doi.org/10.1007/978-1-62703-453-1_15

    Article  CAS  PubMed  Google Scholar 

  65. Sun Q, Chen X, Yu J, Zen K, Zhang CY, Li L (2013) Immune modulatory function of abundant immune-related microRNAs in microvesicles from bovine colostrum. Protein Cell 4(3):197–210. https://doi.org/10.1007/s13238-013-2119-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Chen C, Jiang X, Gu S, Zhang Z (2017) MicroRNA-155 regulates arsenite-induced malignant transformation by targeting Nrf2-mediated oxidative damage in human bronchial epithelial cells. Toxicol Lett 278:38–47. https://doi.org/10.1016/j.toxlet.2017.07.215

    Article  CAS  PubMed  Google Scholar 

  67. Cheng X, Ku CH, Siow RC (2013) Regulation of the Nrf2 antioxidant pathway by microRNAs: new players in micromanaging redox homeostasis. Free Radic Biol Med 64:4–11. https://doi.org/10.1016/j.freeradbiomed.2013.07.025

    Article  CAS  PubMed  Google Scholar 

  68. Smith EJ, Shay KP, Thomas NO, Butler JA, Finlay LF, Hagen TM (2015) Age-related loss of hepatic Nrf2 protein homeostasis: Potential role for heightened expression of miR-146a. Free Radic Biol Med 89:1184–1191. https://doi.org/10.1016/j.freeradbiomed.2015.11.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Tebay LE, Robertson H, Durant ST, Vitale SR, Penning TM, Dinkova-Kostova AT, Hayes JD (2015) Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease. Free Radic Biol Med 88(Pt B):108–146. https://doi.org/10.1016/j.freeradbiomed.2015.06.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Yanaka A (2018) Role of NRF2 in protection of the gastrointestinal tract against oxidative stress. J Clin Biochem Nutr 63(1):18–25. https://doi.org/10.3164/jcbn.17-139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Ma Q (2013) Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 53:401–426. https://doi.org/10.1146/annurev-pharmtox-011112-140320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Lee JM, Johnson JA (2004) An important role of Nrf2-ARE pathway in the cellular defense mechanism. J Biochem Mol Biol 37(2):139–143

    CAS  PubMed  Google Scholar 

  73. Nguyen T, Nioi P, Pickett CB (2009) The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem 284(20):13291–13295. https://doi.org/10.1074/jbc.R900010200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Vanella L, Sanford C Jr, Kim DH, Abraham NG, Ebraheim N (2012) Oxidative stress and heme oxygenase-1 regulated human mesenchymal stem cells differentiation. Int J Hypertens 2012:890671. https://doi.org/10.1155/2012/890671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Wen Z, Liu W, Li X, Chen W, Liu Z, Wen J, Liu Z (2019) A Protective role of the NRF2-Keap1 pathway in maintaining intestinal barrier function. Oxid Med Cell Longev 2019:1759149. https://doi.org/10.1155/2019/1759149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Cheleschi S, De Palma A, Pascarelli NA, Giordano N, Galeazzi M, Tenti S, Fioravanti A (2017) Could oxidative stress regulate the expression of MicroRNA-146a and MicroRNA-34a in human osteoarthritic chondrocyte cultures? Int J Mol Sci. https://doi.org/10.3390/ijms18122660

    Article  PubMed  PubMed Central  Google Scholar 

  77. Adesso S, Russo R, Quaroni A, Autore G, Marzocco S (2018) Astragalus membranaceus extract attenuates inflammation and oxidative stress in intestinal epithelial cells via NF-kappaB activation and Nrf2 response. Int J Mol Sci. https://doi.org/10.3390/ijms19030800

    Article  PubMed  PubMed Central  Google Scholar 

  78. Zhuang S, Yu R, Zhong J, Liu P, Liu Z (2019) Rhein from rheum rhabarbarum inhibits hydrogen-peroxide-induced oxidative stress in intestinal epithelial cells partly through PI3K/Akt-mediated Nrf2/HO-1 pathways. J Agric Food Chem 67(9):2519–2529. https://doi.org/10.1021/acs.jafc.9b00037

    Article  CAS  PubMed  Google Scholar 

  79. Pulkkinen KH, Yla-Herttuala S, Levonen AL (2011) Heme oxygenase 1 is induced by miR-155 via reduced BACH1 translation in endothelial cells. Free Radic Biol Med 51(11):2124–2131. https://doi.org/10.1016/j.freeradbiomed.2011.09.014

    Article  CAS  PubMed  Google Scholar 

  80. Gu S, Lai Y, Chen H, Liu Y, Zhang Z (2017) miR-155 mediates arsenic trioxide resistance by activating Nrf2 and suppressing apoptosis in lung cancer cells. Sci Rep 7(1):12155. https://doi.org/10.1038/s41598-017-06061-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Onodera Y, Teramura T, Takehara T, Obora K, Mori T, Fukuda K (2017) miR-155 induces ROS generation through downregulation of antioxidation-related genes in mesenchymal stem cells. Aging Cell 16(6):1369–1380. https://doi.org/10.1111/acel.12680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Sun J, Aswath K, Schroeder SG, Lippolis JD, Reinhardt TA, Sonstegard TS (2015) MicroRNA expression profiles of bovine milk exosomes in response to Staphylococcus aureus infection. BMC Genom 16(1):806. https://doi.org/10.1186/s12864-015-2044-9

    Article  CAS  Google Scholar 

  83. Li R, Dudemaine PL, Zhao X, Lei C, Ibeagha-Awemu EM (2016) Comparative analysis of the miRNome of bovine milk fat, Whey and Cells. PLoS ONE 11(4):e0154129. https://doi.org/10.1371/journal.pone.0154129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China [Grant Number 21476176], the National Key Technology R&D Program of China [Grant Number 2015BAD16B01], the National High Technology Research and Development Program of China [863 Program, Grant Number 2015AA021002], and the International Science and Technology Cooperation Programs of Anhui [Grant Number 1503062006].

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lanfang Wang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 494 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, L., Shi, Z., Wang, X. et al. Protective effects of bovine milk exosomes against oxidative stress in IEC-6 cells. Eur J Nutr 60, 317–327 (2021). https://doi.org/10.1007/s00394-020-02242-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-020-02242-z

Keywords

Navigation