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Arginine Supplementation Recovered the IFN-γ-Mediated Decrease in Milk Protein and Fat Synthesis by Inhibiting the GCN2/eIF2α Pathway, Which Induces Autophagy in Primary Bovine Mammary Epithelial Cells
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  • Journal title : Molecules and Cells
  • Volume 39, Issue 5,  2016, pp.410-417
  • Publisher : Korea Society for Molecular and Cellular Biology
  • DOI : 10.14348/molcells.2016.2358
 Title & Authors
Arginine Supplementation Recovered the IFN-γ-Mediated Decrease in Milk Protein and Fat Synthesis by Inhibiting the GCN2/eIF2α Pathway, Which Induces Autophagy in Primary Bovine Mammary Epithelial Cells
Xia, Xiaojing; Che, Yanyi; Gao, Yuanyuan; Zhao, Shuang; Ao, Changjin; Yang, Hongjian; Liu, Juxiong; Liu, Guowen; Han, Wenyu; Wang, Yuping; Lei, Liancheng;
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 Abstract
During the lactation cycle of the bovine mammary gland, autophagy is induced in bovine mammary epithelial cells (BMECs) as a cellular homeostasis and survival mechanism. Interferon gamma () is an important antiproliferative and apoptogenic factor that has been shown to induce autophagy in multiple cell lines in vitro. However, it remains unclear whether can induce autophagy and whether autophagy affects milk synthesis in BMECs. To understand whether affects milk synthesis, we isolated and purified primary BMECs and investigated the effect of on milk synthesis in primary BMECs in vitro. The results showed that significantly inhibits milk synthesis and that autophagy was clearly induced in primary BMECs in vitro within 24 h. Interestingly, autophagy was observed following treatment, and the inhibition of autophagy can improve milk protein and milk fat synthesis. Conversely, upregulation of autophagy decreased milk synthesis. Furthermore, mechanistic analysis confirmed that mediated autophagy by depleting arginine and inhibiting the general control nonderepressible-2 kinase (GCN2)/eukaryotic initiation factor () signaling pathway in BMECs. Then, it was found that arginine supplementation could attenuate -induced autophagy and recover milk synthesis to some extent. These findings may not only provide a novel measure for preventing the -induced decrease in milk quality but also a useful therapeutic approach for -associated breast diseases in other animals and humans.
 Keywords
autophagy;arginine;BMECs;;milk synthesis;
 Language
English
 Cited by
1.
Pexophagy is responsible for 65% of cases of peroxisome biogenesis disorders, Autophagy, 2017, 13, 5, 991  crossref(new windwow)
2.
Nutrient sensing and metabolic changes after methionine deprivation in primary muscle cells of turbot ( Scophthalmus maximus L.), The Journal of Nutritional Biochemistry, 2017  crossref(new windwow)
 References
1.
Ahmadinejad, N., Movahedinia, S., Movahedinia, S., Holakouie, N.K., and Nedjat, S. (2013). Distribution of breast density in Iranian women and its association with breast cancer risk factors. Iran Red Crescent Med. J. 15, e16615.

2.
Angcajas, A.B., Hirai, N., Kaneshiro, K., Karim, M.R., Horii, Y., Kubota, M., Fujimura, S., and Kadowaki, M. (2014). Diversity of amino acid signaling pathways on autophagy regulation: a novel pathway for arginine. Biochem. Biophys. Res. Commun. 446, 8-14. crossref(new window)

3.
Bian, Y., Lei, Y., Wang, C., Wang, J., Wang, L., Liu, L., Liu, L., Gao, X., and Li, Q. (2015). Epigenetic regulation of miR-29s affects the lactation activity of dairy cow mammary epithelial cells. J. Cell Physiol. 230, 2152-2163. crossref(new window)

4.
Bionaz, M., and Loor, J.J. (2011). Gene networks driving bovine mammary protein synthesis during the lactation cycle. Bioinform. Biol. Insights 5, 83-98.

5.
Boehm, U., Klamp, T., Groot, M., and Howard, J.C. (1997). Cellular responses to interferon-gamma. Annu. Rev. Immunol. 15, 749-795. crossref(new window)

6.
Borden, E.C., Sen, G.C., Uze, G., Silverman, R.H., Ransohoff, R.M., Foster, G.R., and Stark, G.R. (2007). Interferons at age 50: past, current and future impact on biomedicine. Nat. Rev. Drug Discov. 6, 975-990. crossref(new window)

7.
Bougarn, S., Cunha, P., Gilbert, F.B., Meurens, F., and Rainard, P. (2011). Technical note: Validation of candidate reference genes for normalization of quantitative PCR in bovine mammary epithelial cells responding to inflammatory stimuli. J. Dairy Sci. 94, 2425-2430. crossref(new window)

8.
Fougeray, S., Mami, I., Bertho, G., Beaune, P., Thervet, E., and Pallet, N. (2012). Tryptophan depletion and the kinase GCN2 mediate IFN-gamma-induced autophagy. J. Immunol. 189, 2954-2964. crossref(new window)

9.
Fredericksen, F., Delgado, F., Cabrera, C., Yanez, A., Gonzalo, C., Villalba, M., and Olavarria, V.H. (2015). The effects of reference genes in qRT-PCR assays for determining the immune response of bovine cells (MDBK) infected with the Bovine Viral Diarrhea Virus 1 (BVDV-1). Gene 569, 95-103. crossref(new window)

10.
Gajewska, M., Gajkowska, B., and Motyl, T. (2005). Apoptosis and autophagy induced by TGF-B1 in bovine mammary epithelial BME-UV1 cells. J. Physiol. Pharmacol. 56 Suppl 3, 143-157.

11.
Hannigan, A.M., and Gorski, S.M. (2009). Macroautophagy: the key ingredient to a healthy diet? Autophagy 5, 140-151. crossref(new window)

12.
Harris, J. (2011). Autophagy and cytokines. Cytokine 56, 140-144. crossref(new window)

13.
Hu, H., Wang, J., Bu, D., Wei, H., Zhou, L., Li, F., and Loor, J.J. (2009). In vitro culture and characterization of a mammary epithelial cell line from Chinese Holstein dairy cow. PLoS One 4, e7636. crossref(new window)

14.
Kimmelman, A.C. (2011). The dynamic nature of autophagy in cancer. Genes Dev. 25, 1999-2010. crossref(new window)

15.
Kroemer, G., Marino, G., and Levine, B. (2010). Autophagy and the integrated stress response. Mol. Cell 40, 280-293. crossref(new window)

16.
Lee, H.J., Hinshelwood, R.A., Bouras, T., Gallego-Ortega, D., Valdes-Mora, F., Blazek, K., Visvader, J.E., Clark, S.J., and Ormandy, C.J. (2011). Lineage specific methylation of the Elf5 promoter in mammary epithelial cells. Stem Cells 29, 1611-1619. crossref(new window)

17.
Li, J.X., Zhang, Y., Ma, L.B., Sun, J.H., and Yin, B.Y. (2009). Isolation and culture of bovine mammary epithelial stem cells. J. Vet. Med. Sci. 71, 15-19. crossref(new window)

18.
Mackle T.R., Dwyer D.A., Ingvartsen K.L. Chouinard P.Y., Ross D.A., Bauman D.E. (2000). Effects of insulin and postruminal supply of protein on use of amino acids by the mammary gland for milk protein synthesis. J. Dairy Sci. 83, 93-105. crossref(new window)

19.
Maher, S.G., Romero-Weaver, A.L., Scarzello, A.J., and Gamero, A.M. (2007). Interferon: cellular executioner or white knight? Curr. Med. Chem. 14, 1279-1289. crossref(new window)

20.
Marino, G., and Lopez-Otin, C. (2004). Autophagy: molecular mechanisms, physiological functions and relevance in human pathology. Cell Mol. Life. Sci. 61, 1439-1454.

21.
Motyl, T., Gajewska, M., Zarzynska, J., Sobolewska, A., and Gajkowska, B. (2007). Regulation of autophagy in bovine mammary epithelial cells. Autophagy 3, 484-486. crossref(new window)

22.
Pei, J., Zhao, M., Ye, Z., Gou, H., Wang, J., Yi, L., Dong, X., Liu, W., Luo, Y., Liao, M., and Chen, J. (2014). Autophagy enhances the replication of classical swine fever virus in vitro. Autophagy 10, 93-110. crossref(new window)

23.
Ravikumar, B., Sarkar, S., Davies, J.E., Futter, M., Garcia-Arencibia, M., Green-Thompson, Z.W., Jimenez-Sanchez, M., Korolchuk, V.I., Lichtenberg, M., and Luo, S., et al. (2010). Regulation of mammalian autophagy in physiology and pathophysiology. Physiol. Rev. 90, 1383-1435. crossref(new window)

24.
Rubinsztein, D.C., Marino, G., and Kroemer, G. (2011). Autophagy and aging. Cell 146, 682-695. crossref(new window)

25.
Schmeisser, H., Fey, S.B., Horowitz, J., Fischer, E.R., Balinsky, C.A., Miyake, K., Bekisz, J., Snow, A.L., and Zoon, K.C. (2013). Type I interferons induce autophagy in certain human cancer cell lines. Autophagy 9, 683-696. crossref(new window)

26.
Sobolewska, A., Gajewska, M., Zarzynska, J., Gajkowska, B., and Motyl, T. (2009). IGF-I, EGF, and sex steroids regulate autophagy in bovine mammary epithelial cells via the mTOR pathway. Eur. J. Cell Biol. 88, 117-130. crossref(new window)

27.
Sobolewska, A., Motyl, T., and Gajewska, M. (2011). Role and regulation of autophagy in the development of acinar structures formed by bovine BME-UV1 mammary epithelial cells. Eur. J. Cell Biol. 90, 854-864. crossref(new window)

28.
Wu Y. (2013). Effects of different types of diet on plasma endotoxin and immune activation in dairy goats and dairy cows. Chinas Excellent MA Degree P.

29.
Yang, J., Kennelly, J.J., and Baracos, V.E. (2000). Physiological levels of Stat5 DNA binding activity and protein in bovine mammary gland. J. Anim. Sci. 78, 3126-3134. crossref(new window)

30.
Zhou, J., Dong, G., Ao, C., Zhang, S., Qiu, M., Wang, X., Wu, Y., Erdene, K., Jin, L., Lei, C., and Zhang, Z. (2014). Feeding a high-concentrate corn straw diet increased the release of endotoxin in the rumen and pro-inflammatory cytokines in the mammary gland of dairy cows. BMC Vet. Res. 10. crossref(new window)