Skip to main content
Top
Published in: European Journal of Nutrition 1/2021

01-02-2021 | Original Contribution

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

Authors: Lanfang Wang, Zhexi Shi, Xinyan Wang, Shu Mu, Xiaoyan Xu, Li Shen, Ping Li

Published in: European Journal of Nutrition | Issue 1/2021

Login to get access

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.
Appendix
Available only for authorised users
Literature
3.
go back to reference 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):770–773PubMed 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):770–773PubMed
4.
go back to reference Grisham MB (1994) Oxidants and free radicals in inflammatory bowel disease. Lancet 344(8926):859–861CrossRefPubMed Grisham MB (1994) Oxidants and free radicals in inflammatory bowel disease. Lancet 344(8926):859–861CrossRefPubMed
5.
go back to reference 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):311–322CrossRefPubMed 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):311–322CrossRefPubMed
8.
go back to reference Inokuma T, Haraguchi M, Fujita F, Tajima Y, Kanematsu T (2009) Oxidative stress and tumor progression in colorectal cancer. Hepatogastroenterology 56(90):343–347PubMed Inokuma T, Haraguchi M, Fujita F, Tajima Y, Kanematsu T (2009) Oxidative stress and tumor progression in colorectal cancer. Hepatogastroenterology 56(90):343–347PubMed
10.
go back to reference 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.201500222CrossRefPubMed 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.​201500222CrossRefPubMed
12.
go back to reference 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):1969–1978CrossRefPubMed 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):1969–1978CrossRefPubMed
19.
go back to reference 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/ncomms11106CrossRefPubMedPubMedCentral 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/​ncomms11106CrossRefPubMedPubMedCentral
23.
go back to reference 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.v4.27066CrossRefPubMed 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.​27066CrossRefPubMed
35.
go back to reference 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/nxy223CrossRefPubMedPubMedCentral 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/​nxy223CrossRefPubMedPubMedCentral
39.
go back to reference 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):617–622CrossRefPubMedPubMedCentral 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):617–622CrossRefPubMedPubMedCentral
41.
go back to reference 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.2016.09.014CrossRef 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.​014CrossRef
43.
go back to reference 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):453–459CrossRefPubMed 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):453–459CrossRefPubMed
47.
go back to reference 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.M117.807180CrossRefPubMed 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.​807180CrossRefPubMed
48.
go back to reference 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.2013.01.002CrossRefPubMed 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.​002CrossRefPubMed
72.
go back to reference Lee JM, Johnson JA (2004) An important role of Nrf2-ARE pathway in the cellular defense mechanism. J Biochem Mol Biol 37(2):139–143PubMed Lee JM, Johnson JA (2004) An important role of Nrf2-ARE pathway in the cellular defense mechanism. J Biochem Mol Biol 37(2):139–143PubMed
Metadata
Title
Protective effects of bovine milk exosomes against oxidative stress in IEC-6 cells
Authors
Lanfang Wang
Zhexi Shi
Xinyan Wang
Shu Mu
Xiaoyan Xu
Li Shen
Ping Li
Publication date
01-02-2021
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nutrition / Issue 1/2021
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-020-02242-z

Other articles of this Issue 1/2021

European Journal of Nutrition 1/2021 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.