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Publication : Differential functions of calpain 1 during epithelial cell death and adipocyte differentiation in mammary gland involution.

First Author  Arnandis T Year  2014
Journal  Biochem J Volume  459
Issue  2 Pages  355-68
PubMed ID  24467364 Mgi Jnum  J:212301
Mgi Id  MGI:5578445 Doi  10.1042/BJ20130847
Citation  Arnandis T, et al. (2014) Differential functions of calpain 1 during epithelial cell death and adipocyte differentiation in mammary gland involution. Biochem J 459(2):355-68
abstractText  Calpains become activated in the mammary gland early during weaning, cleaving several proteins located mainly in the cell membrane, but also in other organelles such as lysosomes, mitochondria and nuclei. By immunofluorescence and Western blot analysis, we have demonstrated the nuclear translocation of calpain-1 and calpain-2, together with the cleavage of several cytoplasmic nucleoporins in epithelial cells of the lobulo-alveolar compartment. In vivo and in vitro calpain inhibition prevented this nucleoporin degradation. In addition, calpain-1 was also present in the nucleus of non-epithelial mammary tissue cells, concomitant with adipocyte re-differentiation. Calpain-1 was internalized within nuclei and found to be present in the nuclear chromatin-enriched fraction, associated with histone H3. Furthermore, we have demonstrated, both in vivo and in vitro, the cleavage of the N-terminal residue of histone H3 by calpain-1. Calpain-1 co-localized with both H3K4me3 (histone H3 trimethylated at Lys4) and H3K27me3 (histone H3 trimethylated at Lys27) at the nuclear periphery, a bivalent epigenetic signal essential for cell differentiation. Using ChIP assays we could confirm the presence of calpain-1 in the promoters of key genes expressed in adipose tissue, such as Cebpa (CCAAT/enhancer-binding protein alpha) and Lep (leptin). The results of the present study highlight a dual role for calpain-1 in the weaned gland after the pregnancy/lactation cycle, controlling programmed cell death and participating in the epigenetic programme during adipocyte differentiation.
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