Colostrum oxytocin modulates cellular stress response, inflammation, and autophagy markers in newborn rat gut villi
Abstract
Little is known about the role of oxytocin (OT) in colostrum during early gut colonization. We previously showed that transient OT receptor (OTR) expression on newborn rat enterocytes coincides with the milk-suckling period, and that OT activates endoplasmic reticulum stress sensors in cultured enterocytes. Here, we explored whether colostrum-OT attenuates stress in newborn villi primed and unprimed by colostrum by measuring levels of stress markers including BiP (an ER chaperone), eIF2a (translation initiation factor), and pPKR (eIF2a kinase). We also measured two inflammation-signaling proteins NF-κB and its inhibitor IκB. To test the impact of colostrum on autophagy, we measured a marker of autophagy initiation, LC3A. Colostrum increased inactive p-eIF2a, p-PKR and IκB and reduced p-IκB, BiP and LC3A. LPS increased and OT decreased p-IkB. BiP (GRP78) was higher in unprimed than primed villi. Together, these data suggest that colostrum OT attenuates the impact of inflammation on postnatal gut villi and that OT enhances autophagy to protect against amino acid insufficiency-induced stress during the interval between birth and the first feeding.
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Oxytocin in breastmilk, specifically colostrum which is not found in infant formula, is associated with anti-inflammatory effects in rats.
“Oxytocin in breastmilk, specifically colostrum which is not found in infant formula, is associated with anti-inflammatory effects in rats.”
From The evolved nest, oxytocin functioning, and prosocial development (2023) · cites this paper as Klein et al., 2017
Oxytocin present in colostrum and breastmilk protected the intestinal villi from cellular stress.
“Further, oxytocin present in colostrum and breastmilk protected the intestinal villi from cellular stress.”
From The evolved nest, oxytocin functioning, and prosocial development (2023) · cites this paper as Klein et al., 2017
Oxytocin downregulates inflammation processes by impeding protein translation and the promotion of autophagy.
“Oxytocin also downregulates inflammation processes by impeding protein translation and the promotion of autophagy (the cleaning out of damaged cells).”
From The evolved nest, oxytocin functioning, and prosocial development (2023) · cites this paper as Klein et al., 2017
At least in rats, oxytocin in colostrum and breastmilk may be an important component of building a healthy gut microbiome and reducing inflammation.
“As such, at least in rats, oxytocin in colostrum and breastmilk may be an important component of building a healthy gut microbiome and reducing inflammation.”
From The evolved nest, oxytocin functioning, and prosocial development (2023) · cites this paper as Klein et al., 2017
Oxytocin in breast milk protected enterocytes from apoptotic cell death and supported cellular metabolism to promote enterocyte cell differentiation.
“More specifically, Klein et al. (2017) found that oxytocin in breast milk protected enterocytes (cells in the intestinal lining) from apoptotic cell death and supported cellular metabolism to promote enterocyte cell differentiation (cells becoming individualized for different functions).”
From The evolved nest, oxytocin functioning, and prosocial development (2023) · cites this paper as Klein et al. (2017)
Cites
Hayden, M. S., & Ghosh, S. (2004) · Genes & Development · doi:10.1101/gad.1228704 · Cited by 3,842 · see citing works
Activators and target genes of Rel/NF-κB transcription factors
Pahl, H. L. (1999) · Oncogene · doi:10.1038/sj.onc.1203239 · Cited by 3,727 · see citing works
Activators and Target Genes of Rel/NF-кB Transcription Factors
Loop, T., & Pahl, H. L. (2003) · Springer eBooks · doi:10.1007/978-94-010-0163-2_1 · Cited by 3,179 · see citing works
A C-terminal signal prevents secretion of luminal ER proteins
Munro, S., & Pelham, H. R. B. (1987) · Cell · doi:10.1016/0092-8674(87)90086-9 · Cited by 2,204 · see citing works
Bacterial Imprinting of the Neonatal Immune System: Lessons From Maternal Cells?
Pérez, P. F., Dore, J. M., Leclerc, M., Levenez, F., Benyacoub, J., Serrant, P., Segura-Roggero, I., Schiffrin, E. J., & Donnet‐Hughes, A. (2007) · PEDIATRICS · doi:10.1542/peds.2006-1649 · Cited by 676 · see citing works
TLR Signaling in the Gut in Health and Disease
Abreu, M. T., Fukata, M., & Arditi, M. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.8.4453 · Cited by 577 · see citing works
Hsp90-Tau complex reveals molecular basis for specificity in chaperone action
Karagöz, G. E., Duarte, A. M. S., Akoury, E., Ippel, H., Biernat, J., Morán Luengo, T., Radli, M., Didenko, T., Nordhues, B. A., Veprintsev, D. B., et al. (2014) · Cell · doi:10.1016/j.cell.2014.01.037 · Cited by 318 · see citing works
The amino acid sensor GCN2 controls gut inflammation by inhibiting inflammasome activation
Ravindran, R., Loebbermann, J., Nakaya, H. I., Khan, N., Ma, H., Gama, L., Machiah, D. K., Lawson, B., Hakimpour, P., Wang, Y.-C., et al. (2016) · Nature · doi:10.1038/nature17186 · Cited by 312 · see citing works
Potential role of the intestinal microbiota of the mother in neonatal immune education
Donnet‐Hughes, A., Pérez, P. F., Dore, J. M., Leclerc, M., Levenez, F., Benyacoub, J., Serrant, P., Segura-Roggero, I., & Schiffrin, E. J. (2010) · Proceedings of The Nutrition Society · doi:10.1017/s0029665110001898 · Cited by 216 · see citing works
dsRNA-Dependent Protein Kinase PKR and its Role in Stress, Signaling and HCV Infection
Dabo, S., & MEURS, E. F. (2012) · Viruses · doi:10.3390/v4112598 · Cited by 171 · see citing works
Welch, M. G., Margolis, K. G., Li, Z., & Gershon, M. D. (2014) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00176.2014 · Cited by 152 · see citing works
Self-citationImmune Cell–Mediated Protection of the Mammary Gland and the Infant during Breastfeeding
Hassiotou, F., & Geddes, D. T. (2015) · Advances in Nutrition · doi:10.3945/an.114.007377 · Cited by 145 · see citing works
Activation of the grp78 and grp94 Promoters by Hepatitis C Virus E2 Envelope Protein
Liberman, E., Fong, Y. L., Selby, M., Choo, Q., Cousens, L. S., Houghton, M., & Yen, T. S. B. (1999) · Journal of Virology · doi:10.1128/jvi.73.5.3718-3722.1999 · Cited by 115 · see citing works
Manning, M., Miteva, K., Pancheva, S. N., STOEV, S., Wo, N. C., & Chan, W. Y. (1995) · International journal of peptide & protein research · doi:10.1111/j.1399-3011.1995.tb00596.x · Cited by 99 · see citing works
Chen, J., Heldman, M. R., Herrmann, M. A., Kedei, N., Woo, W., Blumberg, P. M., & Goldsmith, P. K. (2013) · Analytical Biochemistry · doi:10.1016/j.ab.2013.07.022 · Cited by 99 · see citing works
Gene regulation by dietary microRNAs
Zempleni, J., Baier, S. R., Howard, K. M., & Cui, J. (2015) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2014-0392 · Cited by 70 · see citing works
Concentrations and origin of oxytocin in breast milk.
Takeda, S., Kuwabara, Y., & Mizuno, M. (1986) · Endocrinologia Japonica · doi:10.1507/endocrj1954.33.821 · Cited by 69 · see citing works
Breastmilk Cell and Fat Contents Respond Similarly to Removal of Breastmilk by the Infant
Hassiotou, F., Hepworth, A. R., Williams, T. M., Twigger, A., Perrella, S. L., Lai, C. T., Filgueira, L., Geddes, D. T., & Hartmann, P. E. (2013) · PLoS ONE · doi:10.1371/journal.pone.0078232 · Cited by 67 · see citing works
Loughney, J. W., Lancaster, C., Ha, S., & Rustandi, R. R. (2014) · Analytical Biochemistry · doi:10.1016/j.ab.2014.05.004 · Cited by 60 · see citing works
Oxytocin modulates mTORC1 pathway in the gut
Klein, B., Tamir, H., Hirschberg, D. L., Glickstein, S. B., & Welch, M. G. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.01.121 · Cited by 34 · see citing works
Self-citationDetermination of oxytocin in milk of cows administered oxytocin
Prakash, B. S., Paul, V., Kliem, H., Kulozik, U., & Meyer, H. H. D. (2009) · Analytica Chimica Acta · doi:10.1016/j.aca.2009.01.050 · Cited by 33 · see citing works
Solangi, A. R., Memon, S. Q., Mallah, A. B., Khuhawar, M. Y., & Bhanger, M. I. (2009) · Biomedical Chromatography · doi:10.1002/bmc.1215 · Cited by 31 · see citing works
Oxytocin opposes effects of bacterial endotoxin on ER-stress signaling in Caco2BB gut cells.
Klein, B., Tamir, H., Hirschberg, D., Ludwig, R. J., Glickstein, S., Myers, M., & Welch, M. G. (2016) · Biochimica et Biophysica Acta · doi:10.1016/j.bbagen.2015.10.025 · Cited by 26 · see citing works
Self-citationOxytocin modulates markers of the unfolded protein response in Caco2BB gut cells
Klein, B., Tamir, H., Hirschberg, D., Glickstein, S., Ludwig, R. J., & Welch, M. G. (2014) · Cell stress & chaperones (Print) · doi:10.1007/s12192-013-0473-4 · Cited by 14 · see citing works
Self-citationPhospho-proteomic approach to identify new targets of leucine deprivation in muscle cells
Talvas, J., Obled, A., Sayd, T., Chambon, C., Mordier, S. B., & Fafournoux, P. (2008) · Analytical Biochemistry · doi:10.1016/j.ab.2008.05.038 · Cited by 10 · see citing works
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Carter, C. S., Kenkel, W. M., MacLean, E. L., Wilson, S. R., Perkeybile, A. M., Yee, J. R., Ferris, C. F., Nazarloo, H. P., Porges, S. W., Davis, J. M., et al. (2020) · Pharmacological Reviews · doi:10.1124/pr.120.019398 · Cited by 394 · see citing works
Exosome-Derived MicroRNAs of Human Milk and Their Effects on Infant Health and Development
Melnik, B. C., Stremmel, W., Weiskirchen, R., John, S. M., & Schmitz, G. (2021) · Biomolecules · doi:10.3390/biom11060851 · Cited by 194 · see citing works
Wang, P., Wang, S. C., Yang, H.-P., Lv, C., Jia, S., Liu, X., Wang, X., Meng, D., Qin, D., Zhu, H. F., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00454 · Cited by 73 · see citing works
Kingsbury, M. A., & Bilbo, S. D. (2019) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2019.100794 · Cited by 64 · see citing works
Calming Cycle Theory and the Co-Regulation of Oxytocin
Welch, M. G., & Ludwig, R. J. (2017) · Psychodynamic Psychiatry · doi:10.1521/pdps.2017.45.4.519 · Cited by 49 · see citing works
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Self-citationDou, D., Liang, J., Zhai, X., Li, G., Wang, H., Han, L., Lin, L., Ren, Y., Liu, S., Liu, C., et al. (2021) · Clinical Science · doi:10.1042/cs20201438 · Cited by 32 · see citing works
Friuli, M., Eramo, B., Valenza, M., Scuderi, C., Provensi, G., & Romano, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910250 · Cited by 32 · see citing works
Oxytocin and oxygen: the evolution of a solution to the ‘stress of life’
Carter, C. S., & Kingsbury, M. A. (2022) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2021.0054 · Cited by 32 · see citing works
Gross Margolis, K., Vittorio, J., Talavera, M., Gluck, K., Li, Z., Iuga, A., Stevanovic, K., Saurman, V., Israelyan, N., Welch, M. G., et al. (2017) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00215.2017 · Cited by 28 · see citing works
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Bozhkov, A. I., Ohiienko, S. L., Bondar, A. Y., Ivanov, E. G., & Kurguzova, N. I. (2020) · Regulatory Mechanisms in Biosystems · doi:10.15421/022040 · Cited by 3 · see citing works
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Havránek, T., Mihalj, D., Bačová, Z., & Bakoš, J. (2022) · Neuroscience Letters · doi:10.1016/j.neulet.2022.136971 · Cited by 3 · see citing works
Hani, U., Kandagalla, S., Shekarappa, S. B., & Hanumanthappa, M. (2019) · Journal of Proteins and Proteomics · doi:10.1007/s42485-019-00008-8 · Cited by 2 · see citing works
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Muscatelli, F. (2022) · Biologie Aujourd hui · doi:10.1051/jbio/2022017 · Cited by 2 · see citing works
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産業集積地域における大学の経路依存性と産学連携の特質(12月例会,西南支部,例会記録(2012年10月～12月))
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- Authors
- Klein, B. Y., Tamir, H., Ludwig, R. J., Glickstein, S. B., & Welch, M. G.
- Affiliations
- Columbia University Irving Medical Center (US)
- Corresponding author
- Klein, Benjamin Y.
- Welch, Martha G.
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 487
- Issue
- 1
- Pages
- 47-53
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2604859095
- Cited by
- 31
- References
- 25
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 6 · 2020: 3 · 2019: 4 · 2018: 1 · 2017: 2 · 2013: 1
- FWCI
- 2.27
- Type
- journal article
- Language
- en
- Update notices
- erratum (2018-09-05)
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Einhorn Family Charitable Trust
- Fleur Fairman Family
- Columbia University's CTSA
- NCRR/NIH (UL1RR024156)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Health Sciences › Health Professions › Pharmacy › Infant Health and Development
- Keywords
- oxytocin, colostrum, oxytocin receptor, endoplasmic reticulum stress, autophagy, inflammation, enterocytes, neonatal rats, NF-κB, IκB, BiP/GRP78, eIF2A, PKR, LC3A, lipopolysaccharide, intestinal colonization
- MeSH terms
- Endoplasmic Reticulum Chaperone BiP, Animals, Animals, Newborn, Autophagy, Colostrum, Dose-Response Relationship, Drug, Female, Heat-Shock Proteins, Intestinal Mucosa, Male, Microvilli, Oxytocin, Rats, Sprague-Dawley, Inflammation Mediators, Rats, Endoplasmic Reticulum Stress
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