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

Folding variants of alpha-lactalbumin (alpha-la) are known to induce cell death in a number of cell types, including mammary epithelial cells (MEC). The native conformation of alpha-la however has not been observed to exhibit this biological activity. Here we report that native bovine alpha-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 alpha-la in involution and/or maintaining the luminal space in mammary alveoli during lactation. In addition, co-incubation of bovine alpha-la in an in-vitro mammosphere model resulted in decreased beta-casein mRNA expression and increased alphas1- and kappa-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 alpha-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.