Fundamental studies of milk exosomes Camelus dromedarius, Camelus bactrianus and hybrids from Kazakhstan
DOI:
https://doi.org/10.26577/eb.2020.v84.i3.06Abstract
Milk contains extracellular vesicles that are released by udder cells and are recognized as a new mechanism for transmitting information from mother to newborn. In this study, extracellular vesicles were isolated from milk of C. dromedarius, C. bactrianus and hybrids from Kazakhstan using optimized density gradient ultracentrifugation. Vesicles were visualized using transmission electron microscopy and characterized using nanoparticle tracking analysis. The purified extracellular vesicles had a heterogeneous size distribution ranging from 25 to 170 nm in diameter with an average yield of 9.5*108 – 4.2*1010 particles per milliliter of milk. Combining classical and advanced proteomic approaches, a comprehensive proteomic analysis of camel milk vesicles was carried out. One thousand ten (1010) unique proteins have been identified that are involved in various biological processes, including most markers associated with small vesicles. As a result, the extracellular vesicles of camel milk are enriched with exosomal proteins. The most common biological processes have been associated with the synthesis and secretion of exosomes. They are mainly involved in molecular functions such as poly RNA and ATP binding, protein binding and structural constituent of the ribosomes.
Key words: camel milk, exosomes, extracellular vesicles, proteome.
References
1 Colombo, Marina, Graça Raposo, and Clotilde Théry. 2014. “Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other Extracellular Vesicles.” Annual Review of Cell and Developmental Biology 30 (1): 255–89. https://doi.org/10.1146/annurev-cellbio-101512-122326.
2 Kabani, Mehdi, and Ronald Melki. 2016. “More than Just Trash Bins? Potential Roles for Extracellular Vesicles in the Vertical and Horizontal Transmission of Yeast Prions.” Current Genetics. https://doi.org/10.1007/s00294-015-0534-6.
3 Hromada, Carina, Severin Mühleder, Johannes Grillari, Heinz Redl, and Wolfgang Holnthoner. 2017. “Endothelial Extracellular Vesicles-Promises and Challenges.” Frontiers in Physiology. https://doi.org/10.3389/fphys.2017.00275.
4 Pol, E. van der, A. N. Boing, P. Harrison, A. Sturk, and R. Nieuwland. 2012. “Classification, Functions, and Clinical Relevance of Extracellular Vesicles.” Pharmacological Reviews 64 (3): 676–705. https://doi.org/10.1124/pr.112.005983.
5 Abels, E. R., & Breakefield, O. (2016). Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake. Cellular and Molecular Neurobiology, 36(3), 301–312. https://doi.org/10.1007/s10571-016-0366-z
6 Laemmli, U.K. 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 227, 680-685. doi:10.1038/227680a0
7 Witwer, Kenneth W., Edit I. Buzás, Lynne T. Bemis, Adriana Bora, Cecilia Lässer, Jan Lötvall, Esther N. Nolte-’t Hoen, et al. 2013. “Standardization of Sample Collection, Isolation and Analysis Methods in Extracellular Vesicle Research.” Journal of Extracellular Vesicles. https://doi.org/10.3402/jev.v2i0.20360.
8 Zonneveld, Marijke I., Alain R. Brisson, Martijn J.C. van Herwijnen, Sisareuth Tan, Chris H.A. van de Lest, Frank A. Redegeld, Johan Garssen, Marca H.M. Wauben, and Esther Nolte t.N.M. Hoen. 2014. “Recovery of Extracellular Vesicles from Human Breast Milk Is Influenced by Sample Collection and Vesicle Isolation Procedures.” Journal of Extracellular Vesicles. https://doi.
org/10.3402/jev.v3.24215.
9 Yamada, Tetsuya, Yasuo Inoshima, Tsukasa Matsuda, and Naotaka Ishiguro. 2012. “Comparison of Methods for Isolating Exosomes from Bovine Milk.” Journal of Veterinary Medical Science 74 (11): 1523–25. https://doi.org/10.1292/jvms.12-0032.
10 Yassin, Aya M., Marwa I. Abdel Hamid, Omar A. Farid, Hassan Amer, and Mohamad Warda. 2016. “Dromedary Milk Exosomes as Mammary Transcriptome Nano-Vehicle: Their Isolation, Vesicular and Phospholipidomic Characterizations.” Journal of Advanced Research 7 (5): 749–56. https://doi.org/10.1016/j.jare.2015.10.003.
11 Reinhardt, Timothy A., Randy E. Sacco, Brian J. Nonnecke, and John D. Lippolis. 2013. “Bovine Milk Proteome: Quantitative Changes in Normal Milk Exosomes, Milk Fat Globule Membranes and Whey Proteomes Resulting from Staphylococcus Aureus Mastitis.” Journal of Proteomics 82: 141–54. https://doi.org/10.1016/j.jprot.2013.02.013.
12 Chen, Ting, Mei Ying Xie, Jia Jie Sun, Rui Song Ye, Xiao Cheng, Rui Ping Sun, Li Min Wei, et al. 2016. “Porcine Milk-Derived Exosomes Promote Proliferation of Intestinal Epithelial Cells.” Scientific Reports 6. https://doi.org/10.1038/srep33862.
13 Sedykh, Sergey E., Lada V. Purvinish, Artem S. Monogarov, Evgeniya E. Burkova, Alina E. Grigor’eva, Dmitrii V. Bulgakov, Pavel S. Dmitrenok, Valentin V. Vlassov, Elena I. Ryabchikova, and Georgy A. Nevinsky. 2017. “Purified Horse Milk Exosomes Contain an Unpredictable Small Number of Major Proteins.” Biochimie Open 4: 61–72. https://doi.org/10.1016/j.biopen. 2017.02.004.
14 Admyre, C., S. M. Johansson, K. R. Qazi, J.-J.r Filen, R. Lahesmaa, M. Norman, E. P. A. Neve, A. Scheynius, and S. Gabrielsson. 2007. “Exosomes with Immune Modulatory Features Are Present in Human Breast Milk.” The Journal of Immunology 179 (3): 1969–78. https://doi.org/10.4049/jimmunol.179.3.1969.
15 Ryskaliyeva A., Henry C., Miranda G., Faye B., Konuspayeva G., Martin P. 2018. Combining different proteomic approaches to resolve complexity of the milk protein fraction of dromedary, Bactrian camels and hybrids, from different regions of Kazakhstan. PloS ONE 13(5): e0197026. 1-26. http://doi.org/10.1371/journal.pone.0197026. May 10, 2018.
16 Reinhardt, Timothy A., John D. Lippolis, Brian J. Nonnecke, and Randy E. Sacco. 2012. “Bovine Milk Exosome Proteome.” Journal of Proteomics 75 (5): 1486–92. https://doi.org/10.1016/j.jprot.2011.11.017.
17 Ryskaliyeva A., Henry C., Miranda G., Faye B., Konuspayeva G., Martin P. 2019. Alternative splicing events expand molecular diversity of camel CSN1S2 increasing its ability to generate potentially bioactive peptides. Scientific reports, 9:5243, 1-13, https://doi.org/10.1038/s41598-019-41649-5
18 Kuhajda, F P. 2000. “Fatty-Acid Synthase and Human Cancer: New Perspectives on Its Role in Tumor Biology.” Nutrition (Burbank, Los Angeles County, Calif.) 16 (3): 202–8. https://doi.org/10.1016/S0899-9007(99)00266-X.
19 Samuel, Monisha, David Chisanga, Michael Liem, Shivakumar Keerthikumar, Sushma Anand, Ching Seng Ang, Christopher G. Adda, Ellen Versteegen, Markandeya Jois, and Suresh Mathivanan. 2017. “Bovine Milk-Derived Exosomes from Colostrum Are Enriched with Proteins Implicated in Immune Response and Growth.” Scientific Reports 7 (1). https://doi.org/10.1038/s41598-017-06288-8.
20 Baietti, Maria Francesca, Zhe Zhang, Eva Mortier, Aurélie Melchior, Gisèle Degeest, Annelies Geeraerts, Ylva Ivarsson, et al. 2012. “Syndecan-Syntenin-ALIX Regulates the Biogenesis of Exosomes.” Nature Cell Biology 14 (7): 677–85. https://doi. org/10.1038/ncb2502.
21 Raimondo, Francesca, Lavinia Morosi, Clizia Chinello, Fulvio Magni, and Marina Pitto. 2011. “Advances in Membranous Vesicle and Exosome Proteomics Improving Biological Understanding and Biomarker Discovery.” Proteomics. https://doi.org/10.1002/pmic.201000422.
22 Kowal, Joanna, Guillaume Arras, Marina Colombo, Mabel Jouve, Jakob Paul Morath, Bjarke Primdal-Bengtson, Florent Dingli, Damarys Loew, Mercedes Tkach, and Clotilde Théry. 2016. “Proteomic Comparison Defines Novel Markers to Characterize Heterogeneous Populations of Extracellular Vesicle Subtypes.” Proceedings of the National Academy of Sciences 113 (8): E968–77. https://doi.org/10.1073/pnas.1521230113.
23 Keller, Sascha, Michael P. Sanderson, Alexander Stoeck, and Peter Altevogt. 2006. “Exosomes: From Biogenesis and Secretion to Biological Function.” Immunology Letters. https://doi.org/10.1016/j.imlet.2006.09.005.
24 Kanada, Masamitsu, Michael H. Bachmann, Jonathan W. Hardy, Daniel Omar Frimannson, Laura Bronsart, Andrew Wang, Matthew D. Sylvester, et al. 2015. “Differential Fates of Biomolecules Delivered to Target Cells via Extracellular Vesicles.” Proceedings of the National Academy of Sciences, 201418401. https://doi.org/10.1073/pnas.1418401112.
25 Munagala, Radha, Farrukh Aqil, Jeyaprakash Jeyabalan, and Ramesh C. Gupta. 2016. “Bovine Milk-Derived Exosomes for Drug Delivery.” Cancer Letters 371 (1): 48–61. https://doi.org/10.1016/j.canlet.2015.10.020.
2 Kabani, Mehdi, and Ronald Melki. 2016. “More than Just Trash Bins? Potential Roles for Extracellular Vesicles in the Vertical and Horizontal Transmission of Yeast Prions.” Current Genetics. https://doi.org/10.1007/s00294-015-0534-6.
3 Hromada, Carina, Severin Mühleder, Johannes Grillari, Heinz Redl, and Wolfgang Holnthoner. 2017. “Endothelial Extracellular Vesicles-Promises and Challenges.” Frontiers in Physiology. https://doi.org/10.3389/fphys.2017.00275.
4 Pol, E. van der, A. N. Boing, P. Harrison, A. Sturk, and R. Nieuwland. 2012. “Classification, Functions, and Clinical Relevance of Extracellular Vesicles.” Pharmacological Reviews 64 (3): 676–705. https://doi.org/10.1124/pr.112.005983.
5 Abels, E. R., & Breakefield, O. (2016). Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake. Cellular and Molecular Neurobiology, 36(3), 301–312. https://doi.org/10.1007/s10571-016-0366-z
6 Laemmli, U.K. 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 227, 680-685. doi:10.1038/227680a0
7 Witwer, Kenneth W., Edit I. Buzás, Lynne T. Bemis, Adriana Bora, Cecilia Lässer, Jan Lötvall, Esther N. Nolte-’t Hoen, et al. 2013. “Standardization of Sample Collection, Isolation and Analysis Methods in Extracellular Vesicle Research.” Journal of Extracellular Vesicles. https://doi.org/10.3402/jev.v2i0.20360.
8 Zonneveld, Marijke I., Alain R. Brisson, Martijn J.C. van Herwijnen, Sisareuth Tan, Chris H.A. van de Lest, Frank A. Redegeld, Johan Garssen, Marca H.M. Wauben, and Esther Nolte t.N.M. Hoen. 2014. “Recovery of Extracellular Vesicles from Human Breast Milk Is Influenced by Sample Collection and Vesicle Isolation Procedures.” Journal of Extracellular Vesicles. https://doi.
org/10.3402/jev.v3.24215.
9 Yamada, Tetsuya, Yasuo Inoshima, Tsukasa Matsuda, and Naotaka Ishiguro. 2012. “Comparison of Methods for Isolating Exosomes from Bovine Milk.” Journal of Veterinary Medical Science 74 (11): 1523–25. https://doi.org/10.1292/jvms.12-0032.
10 Yassin, Aya M., Marwa I. Abdel Hamid, Omar A. Farid, Hassan Amer, and Mohamad Warda. 2016. “Dromedary Milk Exosomes as Mammary Transcriptome Nano-Vehicle: Their Isolation, Vesicular and Phospholipidomic Characterizations.” Journal of Advanced Research 7 (5): 749–56. https://doi.org/10.1016/j.jare.2015.10.003.
11 Reinhardt, Timothy A., Randy E. Sacco, Brian J. Nonnecke, and John D. Lippolis. 2013. “Bovine Milk Proteome: Quantitative Changes in Normal Milk Exosomes, Milk Fat Globule Membranes and Whey Proteomes Resulting from Staphylococcus Aureus Mastitis.” Journal of Proteomics 82: 141–54. https://doi.org/10.1016/j.jprot.2013.02.013.
12 Chen, Ting, Mei Ying Xie, Jia Jie Sun, Rui Song Ye, Xiao Cheng, Rui Ping Sun, Li Min Wei, et al. 2016. “Porcine Milk-Derived Exosomes Promote Proliferation of Intestinal Epithelial Cells.” Scientific Reports 6. https://doi.org/10.1038/srep33862.
13 Sedykh, Sergey E., Lada V. Purvinish, Artem S. Monogarov, Evgeniya E. Burkova, Alina E. Grigor’eva, Dmitrii V. Bulgakov, Pavel S. Dmitrenok, Valentin V. Vlassov, Elena I. Ryabchikova, and Georgy A. Nevinsky. 2017. “Purified Horse Milk Exosomes Contain an Unpredictable Small Number of Major Proteins.” Biochimie Open 4: 61–72. https://doi.org/10.1016/j.biopen. 2017.02.004.
14 Admyre, C., S. M. Johansson, K. R. Qazi, J.-J.r Filen, R. Lahesmaa, M. Norman, E. P. A. Neve, A. Scheynius, and S. Gabrielsson. 2007. “Exosomes with Immune Modulatory Features Are Present in Human Breast Milk.” The Journal of Immunology 179 (3): 1969–78. https://doi.org/10.4049/jimmunol.179.3.1969.
15 Ryskaliyeva A., Henry C., Miranda G., Faye B., Konuspayeva G., Martin P. 2018. Combining different proteomic approaches to resolve complexity of the milk protein fraction of dromedary, Bactrian camels and hybrids, from different regions of Kazakhstan. PloS ONE 13(5): e0197026. 1-26. http://doi.org/10.1371/journal.pone.0197026. May 10, 2018.
16 Reinhardt, Timothy A., John D. Lippolis, Brian J. Nonnecke, and Randy E. Sacco. 2012. “Bovine Milk Exosome Proteome.” Journal of Proteomics 75 (5): 1486–92. https://doi.org/10.1016/j.jprot.2011.11.017.
17 Ryskaliyeva A., Henry C., Miranda G., Faye B., Konuspayeva G., Martin P. 2019. Alternative splicing events expand molecular diversity of camel CSN1S2 increasing its ability to generate potentially bioactive peptides. Scientific reports, 9:5243, 1-13, https://doi.org/10.1038/s41598-019-41649-5
18 Kuhajda, F P. 2000. “Fatty-Acid Synthase and Human Cancer: New Perspectives on Its Role in Tumor Biology.” Nutrition (Burbank, Los Angeles County, Calif.) 16 (3): 202–8. https://doi.org/10.1016/S0899-9007(99)00266-X.
19 Samuel, Monisha, David Chisanga, Michael Liem, Shivakumar Keerthikumar, Sushma Anand, Ching Seng Ang, Christopher G. Adda, Ellen Versteegen, Markandeya Jois, and Suresh Mathivanan. 2017. “Bovine Milk-Derived Exosomes from Colostrum Are Enriched with Proteins Implicated in Immune Response and Growth.” Scientific Reports 7 (1). https://doi.org/10.1038/s41598-017-06288-8.
20 Baietti, Maria Francesca, Zhe Zhang, Eva Mortier, Aurélie Melchior, Gisèle Degeest, Annelies Geeraerts, Ylva Ivarsson, et al. 2012. “Syndecan-Syntenin-ALIX Regulates the Biogenesis of Exosomes.” Nature Cell Biology 14 (7): 677–85. https://doi. org/10.1038/ncb2502.
21 Raimondo, Francesca, Lavinia Morosi, Clizia Chinello, Fulvio Magni, and Marina Pitto. 2011. “Advances in Membranous Vesicle and Exosome Proteomics Improving Biological Understanding and Biomarker Discovery.” Proteomics. https://doi.org/10.1002/pmic.201000422.
22 Kowal, Joanna, Guillaume Arras, Marina Colombo, Mabel Jouve, Jakob Paul Morath, Bjarke Primdal-Bengtson, Florent Dingli, Damarys Loew, Mercedes Tkach, and Clotilde Théry. 2016. “Proteomic Comparison Defines Novel Markers to Characterize Heterogeneous Populations of Extracellular Vesicle Subtypes.” Proceedings of the National Academy of Sciences 113 (8): E968–77. https://doi.org/10.1073/pnas.1521230113.
23 Keller, Sascha, Michael P. Sanderson, Alexander Stoeck, and Peter Altevogt. 2006. “Exosomes: From Biogenesis and Secretion to Biological Function.” Immunology Letters. https://doi.org/10.1016/j.imlet.2006.09.005.
24 Kanada, Masamitsu, Michael H. Bachmann, Jonathan W. Hardy, Daniel Omar Frimannson, Laura Bronsart, Andrew Wang, Matthew D. Sylvester, et al. 2015. “Differential Fates of Biomolecules Delivered to Target Cells via Extracellular Vesicles.” Proceedings of the National Academy of Sciences, 201418401. https://doi.org/10.1073/pnas.1418401112.
25 Munagala, Radha, Farrukh Aqil, Jeyaprakash Jeyabalan, and Ramesh C. Gupta. 2016. “Bovine Milk-Derived Exosomes for Drug Delivery.” Cancer Letters 371 (1): 48–61. https://doi.org/10.1016/j.canlet.2015.10.020.
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Ryskalieva, A., Krupova, Z., Henry, C., Faye, B., Konuspayeva, G. S., & Martin, P. (2020). Fundamental studies of milk exosomes Camelus dromedarius, Camelus bactrianus and hybrids from Kazakhstan. Experimental Biology, 84(3), 62–73. https://doi.org/10.26577/eb.2020.v84.i3.06
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