Submitted to: Biochemical and Biophysical Research Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/17/2008
Publication Date: 1/2/2009
Citation: Reinhardt, T.A., Lippolis, J.D. 2009. Mammary gland involution is associated with rapid down regulation of major mammary Ca**2+-ATPases. Biochemical and Biophysical Research Communications. 378(1):99-102.
Interpretive Summary: At the end of a lactation cycle, the dairy cow is dried off (milk production is stopped) in preparation for the next lactation. This dry period results in renewal and remodeling of the mammary gland in preparation for the next lactation cycle. It is also called mammary involution. Mammary involution is a critical process for renewal of mammary tissue as described above, but this is also an important period for mammary gland health. The period of initial mammary involution is a time that is known to be important with regard to the introduction of new intra-mammary infections (IMI), which then manifest themselves in the following lactation period. It is also known that the speed of mammary involution is important in preventing new IMI. Therefore factors regulating the start of involution are critical to mammary health in subsequent lactations. The results of this study show that the abrupt loss of calcium pumps at dry off that are required by the mammary gland to regulate the large amount of calcium associated with milk production lead to accumulation of cell calcium and play a part in signaling mammary involution. Therefore loss of mammary calcium homeostasis is critical to initiation of rapid mammary involution and likely mammary health.
Technical Abstract: Sixty percent of calcium in milk is transported across the mammary cells apical membrane by the plasma membrane Ca**2+-ATPase 2 (PMCA2). The effect of abrupt cessation of milk production on the Ca**2+-ATPases and mammary calcium transport is unknown. We found that 24 hours after stopping milk production, PMCA2 and secretory pathway Ca**2+-ATPases 1 and 2 (SPCA1 & 2) expression decreased 80-95%. PMCA4 and Sarco/Endoplasmic Reticulum Ca**2+-ATPase 2 (SERCA2) expression increased with the loss of PMCA2, SPCA1, and SPCA2, but did not increase until 72-96 hours of involution. The rapid loss of these Ca**2+-ATPases occurs at a time of high mammary tissue calcium. These results suggest that the abrupt loss of Ca**2+-ATPases, required by the mammary gland to regulate the large amount of calcium associated with milk production, could lead to accumulation of cell calcium, mitochondria Ca**2+ overload, calcium mediated cell death, and thus play a part in early signaling of mammary involution.