Hostname: page-component-586b7cd67f-dsjbd Total loading time: 0 Render date: 2024-11-23T22:47:15.791Z Has data issue: false hasContentIssue false

The role of native bovine α-lactalbumin in bovine mammary epithelial cell apoptosis and casein expression

Published online by Cambridge University Press:  04 August 2008

Lisa G Riley*
Affiliation:
Centre for Advanced Technologies in Animal Genetics and Reproduction (ReproGen), Faculty of Veterinary Science, University of Sydney, Camden, NSW 2570, Australia Cooperative Research Centre for Innovative Dairy Products, University of Sydney, Camden, NSW 2570, Australia
Peter C Wynn
Affiliation:
Centre for Advanced Technologies in Animal Genetics and Reproduction (ReproGen), Faculty of Veterinary Science, University of Sydney, Camden, NSW 2570, Australia Cooperative Research Centre for Innovative Dairy Products, University of Sydney, Camden, NSW 2570, Australia
Peter Williamson
Affiliation:
Centre for Advanced Technologies in Animal Genetics and Reproduction (ReproGen), Faculty of Veterinary Science, University of Sydney, Camden, NSW 2570, Australia Cooperative Research Centre for Innovative Dairy Products, University of Sydney, Camden, NSW 2570, Australia
Paul A Sheehy
Affiliation:
Centre for Advanced Technologies in Animal Genetics and Reproduction (ReproGen), Faculty of Veterinary Science, University of Sydney, Camden, NSW 2570, Australia Cooperative Research Centre for Innovative Dairy Products, University of Sydney, Camden, NSW 2570, Australia
*
*For correspondence; e-mail: [email protected]

Abstract

Folding variants of α-lactalbumin (α-la) are known to induce cell death in a number of cell types, including mammary epithelial cells (MEC). The native conformation of α-la however has not been observed to exhibit this biological activity. Here we report that native bovine α-la reduced the viability of primary bovine mammary epithelial cells (BMEC) and induced caspase activity in mammospheres, which are alveolar-like structures formed by culturing primary BMEC on extracellular matrix in the presence of lactogenic hormones. These observations suggest a possible role for bovine α-la in involution and/or maintaining the luminal space in mammary alveoli during lactation. In addition, co-incubation of bovine α-la in an in-vitro mammosphere model resulted in decreased β-casein mRNA expression and increased αs1- and κ-casein mRNA expression. This differential effect on casein expression levels is unusual and raises the possibility of manipulating expression levels of individual caseins to alter dairy processing properties. Manipulation of α-la levels could be further investigated for its potential to enhance milk protein expression and/or improve lactational persistency by influencing the balance between proliferation and apoptosis of BMEC, which has a major influence on the milk-producing capacity of the mammary gland.

Type
Research Article
Copyright
Copyright © Proprietors of Journal of Dairy Research 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alexander, L, Stewart, A, Mackinlay, A, Kapelinkskaya, T, Tkach, T & Gorodetsky, S 1988 Isolation and characterization of the bovine κ-casein gene. European Journal of Biochemistry 178 395401CrossRefGoogle ScholarPubMed
Baltzer, A, Svanborg, C & Jaggi, R 2004 Apoptotic cell death in the lactating mammary gland is enhanced by a folding variant of α-lactalbumin. Cellular and Molecular Life Sciences 61 12211228Google ScholarPubMed
Blum, J, Zeigler, M & Wicha, M 1989 Regulation of mammary differentiation by the extracellular matrix. Environmental Health Perspectives 80 7183CrossRefGoogle ScholarPubMed
Boutinaud, M, Guinard-Flament, J & Jammes, H 2004 The number and activity of mammary epithelial cells, determining factors for milk production. Reproduction, Nutrition and Development 44 499508CrossRefGoogle ScholarPubMed
Capuco, A, Wood, D, Baldwin, R, Mcleod, K & Paape, M 2001 Mammary cell number, proliferation, and apoptosis during a bovine lactation: relation to milk production and effect on bST. Journal of Dairy Science 84 21772187CrossRefGoogle ScholarPubMed
Debnath, J, Mills, KR, Collins, NL, Reginato, MJ, Muthuswamy, SK & Brugge, JS 2002 The role of apoptosis in creating and maintaining luminal space within normal and oncogene-expressing mammary acini. Cell 111 2940CrossRefGoogle ScholarPubMed
German, T & Barash, I 2002 Characterization of an epithelial cell line from bovine mammary gland. In Vitro Cellular and Developmental Biology 38 2822922.0.CO;2>CrossRefGoogle ScholarPubMed
Goodman, R & Schanbacher, F 1991 Bovine lactoferrin mRNA: sequence, analysis, and expression in the mammary gland. Biochemical and Biophysical Research Communications 180 7584CrossRefGoogle ScholarPubMed
Hallgren, O, Gustafsson, L, Irjala, H, Selivanova, G, Orrenius, S & Svanborg, C 2006 HAMLET triggers apoptosis but tumour cell death is independent of caspases, BCL-2 and p53. Apoptosis 11 221233CrossRefGoogle ScholarPubMed
Hill, J 1993 The relationship between β-lactoglobulin phenotypes and milk composition in New Zealand dairy cattle. Journal of Dairy Science 76 281286CrossRefGoogle Scholar
Jin, Z & El-Deiry, W 2005 Overview of cell death signaling pathways. Cancer Biology and Therapy 4 139163CrossRefGoogle ScholarPubMed
Kohler, C, Gogvadze, V, Hakansson, A, Svanborg, C, Orrenius, S & Zhivotovsky, B 2001 A folding variant of human α-lactalbumin induces mitochondrial permeability transition in isolated mitochondria. European Journal of Biochemistry 268 186191CrossRefGoogle ScholarPubMed
Kumar, S, Clarke, A, Hooper, M, Horne, D, Law, A, Leaver, J, Springbett, A, Stevenson, E & Simons, J 1994 Milk composition and lactation of β-casein deficient mice. Proceedings of the National Academy of Sciences, USA 91 61386142CrossRefGoogle ScholarPubMed
Laemmli, U 1970 Cleavage of structural proteins during the assembly of the head of the bacteriophage T4. Nature 227 680685CrossRefGoogle ScholarPubMed
Mok, K, Pettersson, J, Orrenius, S & Svanborg, C 2007 HAMLET, protein folding, and tumor cell death. Biomedical and Biophysical Research Communications 354 17CrossRefGoogle ScholarPubMed
Motyl, T, Gajkowska, B, Zarzynska, J, Gajewska, M & Lamparska-Przybysz, M 2006 Apoptosis and autophagy in mammary gland remodeling and breast cancer chemotherapy. Journal of Physiology and Pharmacology 57 1732Google ScholarPubMed
Permyakov, E & Berliner, L 2000 α-Lactalbumin: structure and function. FEBS Letters 473 269274CrossRefGoogle ScholarPubMed
Permyakov, S, Pershikova, I, Khokhlova, T, Uversky, V & Permyakov, E 2004 No need to be HAMLET or BAMLET to interact with histones: binding of monomeric α-lactalbumin to histones and basic poly-amino acids. Biochemistry 43 55755582CrossRefGoogle ScholarPubMed
Pettersson, J, Mossberg, A & Svanborg, C 2006 α-Lactalbumin species variation, HAMLET formation and tumour cell death. Biochemical and Biophysical Research Communications 345 260270CrossRefGoogle Scholar
Rijnkels, M, Kooiman, P, de Boer, H & Pieper, F 1997 Organization of the bovine casein locus. Mammalian Genome 8 148152CrossRefGoogle Scholar
Rijnkels, M, Kooiman, P, Krimpenfort, P, de Boer, H & Pieper, F 1995 Expression analysis of the individual bovine β-, αS2- and κ-casein genes in transgenic mice. Biochemical Journal 311 929937CrossRefGoogle Scholar
Riley, L, Williamson, P, Wynn, P & Sheehy, P 2008 Lactoferrin decreases primary bovine mammary epithelial cell viability and casein expression. Journal of Dairy Research 75 17Google ScholarPubMed
Schmidhauser, C, Bissell, M, Myers, C & Casperson, G 1990 Extracellular matrix and hormones transcriptionally regulate bovine β-casein 5' sequences in stably transfected mouse mammary cells. Proceedings of the National Academy of Sciences, USA 87 91189122CrossRefGoogle ScholarPubMed
Sheehy, P, Della-Vedova, J, Nicholas, K & Wynn, P 2004 Hormone-dependent milk protein gene expression in bovine mammary explants from biopsies at different stages of pregnancy. Journal of Dairy Research 71 135140CrossRefGoogle ScholarPubMed
Shekar, P, Goel, S, Rani, D, Sarathi, D, Alex, J, Singh, S & Kumar, S 2006 κ-casein deficient mice fail to lactate. Proceedings of the National Academy of Sciences, USA 103 80008005CrossRefGoogle ScholarPubMed
Southgate, I, Pitt, E & Trejdosiewicz, L 1996 The effects of dietary fatty acids on the proliferation of normal human urothelial cells in vitro. British Journal of Cancer 74 728734CrossRefGoogle ScholarPubMed
Svanborg, C, Agerstam, H, Aronson, A, Bjerkvig, R, Duringer, C, Fischer, W, Gustafsson, L, Hallgren, O, Leijonhuvud, I, Linse, S, Mossberg, A, Nilsson, H, Pettersson, J & Svensson, M 2003 HAMLET kills tumor cells by an apoptosis-like mechanism-cellular, molecular, and therapeutic aspects. Advances in Cancer Research 88 129CrossRefGoogle ScholarPubMed
Svensson, M, Sabharwal, H, Hakansson, A, Mossberg, A, Lipniunas, P, Leffler, H, Svanborg, C & Linse, S 1999 Molecular characterization of α-lactalbumin folding variants that induce apoptosis in tumor cells. Journal of Biological Chemistry 274 63886396CrossRefGoogle ScholarPubMed
Swaisgood, H 1995 Nitrogenous components of milk. In Handbook of Milk Composition, p. 465 (Ed.Jensen, R). San Diego CA, USA: Academic PressGoogle Scholar
Thompson, M, Farrell, H, Mohanam, S, Liu, S, Kidwell, W, Bansal, M, Cook, R, Medina, D, Kotts, C & Bano, M 1992 Identification of human milk α-lactalbumin as a cell growth inhibitor. Protoplasma 167 134144CrossRefGoogle Scholar
Thompson, M, Groves, M, Brower, D, Farrell, H, Jenness, R & Kotts, C 1988 The calcium-dependent electrophoretic shift of α-lactalbumin, the modifier protein of galactosyl transferase. Biochemical and Biophysical Research Communications 157 944948CrossRefGoogle ScholarPubMed
Wehbi, Z, Perez, M, Sanchez, L, Pocovi, C, Barbana, C & Calvo, M 2005 Effect of heat treatment on denaturation of bovine α-lactalbumin: determination of kinetic and thermodynamic parameters. Journal of Agricultural Food Chemistry 53 97309736CrossRefGoogle ScholarPubMed
Wheeler, M 2003 Production of transgenic livestock: promise fulfilled. Journal of Animal Science 81 3237CrossRefGoogle ScholarPubMed
Wilde, C, Addey, C, Boddy, L & Peaker, M 1995 Autocrine regulation of milk secretion by a protein in milk. Biochemical Journal 305 5158CrossRefGoogle ScholarPubMed
Wilde, C, Addey, C, Li, P & Fernig, D 1997 Programmed cell death in bovine mammary tissue during lactation and involution. Experimental Physiology 82 943953CrossRefGoogle ScholarPubMed
Wilde, C, Knight, C & Flint, D 1999 Control of milk secretion and apoptosis during mammary involution. Journal of Mammary Gland Biology and Neoplasia 4 129136CrossRefGoogle ScholarPubMed
Xu, M, Sugiura, Y, Nagaoka, S & Kanamaru, Y 2005 IEC-6 intestinal cell death induced by bovine milk α-lactalbumin. Bioscience, Biotechnology, Biochemistry 69 10821089CrossRefGoogle ScholarPubMed