Search results for "Mammary gland involution"
showing 9 items of 9 documents
Differential functions of calpain 1 during epithelial cell death and adipocyte differentiation in mammary gland involution
2014
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 wi…
Calpains mediate epithelial-cell death during mammary gland involution: mitochondria and lysosomal destabilization.
2012
Our aim was to elucidate the physiological role of calpains (CAPN) in mammary gland involution. Both CAPN-1 and -2 were induced after weaning and its activity increased in isolated mitochondria and lysosomes. CAPN activation within the mitochondria could trigger the release of cytochrome c and other pro-apoptotic factors, whereas in lysosomes it might be essential for tissue remodeling by releasing cathepsins into the cytosol. Immunohistochemical analysis localized CAPNs mainly at the luminal side of alveoli. During weaning, CAPNs translocate to the lysosomes processing membrane proteins. To identify these substrates, lysosomal fractions were treated with recombinant CAPN and cleaved produc…
Nitration of cathepsin D enhances its proteolytic activity during mammary gland remodelling after lactation
2009
Proteomic studies in the mammary gland of control lactating and weaned rats have shown that there is an increased pattern of nitrated proteins during weaning when compared with controls. Here we report the novel finding that cathepsin D is nitrated during weaning. The expression and protein levels of this enzyme are increased after 8 h of litter removal and this up-regulation declines 5 days after weaning. However, there is a marked delay in cathepsin D activity since it does not increase until 2 days post-weaning and remains high thereafter. In order to find out whether nitration of cathepsin D regulates its activity, iNOS (inducible nitric oxide synthase)−/− mice were used. The expression…
Subcellular distribution of calpain-1 and calpain-2 as a key event for calpain-mediated functions in physiological and neoplastic mammary models
2019
Calpains are a family of calcium-dependent proteases, which modulate their substrates rather than degrade them in such a way that modifies them. Calpains deregulations have been determined as an aggravating factor of different diseases, including cancer. Nevertheless, there are no clear records about the particular contribution of each calpain isoform in physiological processes and how these isoforms are deregulated in pathological conditions. In vivo, each calpain isoform recognizes specific proteins as substrates, and it has been suggested that calpains subcellular localization might determine their substrate recognition, and consequently their functions. In the present study we have expl…
NF-ĸB as node for signal amplification during weaning.
2011
Post-lactational involution has been reported to share common features with breast tumor development. A deep characterization of the signaling triggered after weaning would help to unveil the complex relationship between involution and breast cancer. NF-κB, a crucial factor in the involuting gland, might be an important regulatory node for signal amplification after weaning; however there is limited information about the identity of NF-κB-target genes and the molecular mechanisms leading to the selection of genes involved in a particular biological process. We identified 4532 target genes in mammary gland at 48h weaning, by genome-wide analysis of regions bound by RelA(p65)-NF-κB in vivo. I…
Nitric oxide triggers mammary gland involution after weaning: remodelling is delayed but not impaired in mice lacking inducible nitric oxide synthase
2010
During mammary gland involution, different signals are required for apoptosis and tissue remodelling. To explore the role of NO in the involution of mammary tissue after lactation, NOS2 (inducible nitric oxide synthase)-KO (knockout) mice were used. No apparent differences were observed between NOS2-KO and WT (wild-type) animals during pregnancy and lactation. However, upon cessation of lactation, a notable delay in involution was observed, compared with WT mice. NOS2-KO mice showed increased phosphorylation of STAT (signal transducer and activator of transcription) 5 during weaning, concomitant with increased beta-casein mRNA levels when compared with weaned WT glands, both hallmarks of th…
Retinoids induce MMP-9 expression through RARalpha during mammary gland remodeling.
2007
Retinoic acid (RA) is a signaling molecule in the morphogenesis of the mammary gland, modulating the expression of matrix metalloproteinases (MMPs). The aim of this paper was to study the role of RA during weaning, which consists of three events: apoptosis of the secretory cells, degradation of the extracellular matrix, and adipogenesis. CRABP II and CRBP-1 carrier proteins increased significantly during weaning compared with lactating glands but reverted to control values after the litter resuckled. The effects of RA are mediated by the nuclear receptors RARalpha, RARbeta, RARgamma, and RXRalpha, which underwent an increase in protein levels during weaning. In an attempt to elucidate the R…
Involvement of Different networks in mammary gland involution after the pregnancy/lactation cycle: Implications in breast cancer
2015
Early pregnancy is associated with a reduction in a woman's lifetime risk for breast cancer. However, different studies have demonstrated an increase in breast cancer risk in the years immediately following pregnancy. Early and long-term risk is even higher if the mother age is above 35 years at the time of first parity. The proinflammatory microenvironment within the mammary gland after pregnancy renders an "ideal niche" for oncogenic events. Signaling pathways involved in programmed cell death and tissue remodeling during involution are also activated in breast cancer. Herein, the major signaling pathways involved in mammary gland involution, signal transducer and activator of transcripti…
Role of the NF-kB pathway and nitric oxide in mammary gland involution after weaning. Implications in breast cancer
2013
INTRODUCCIÓN La glándula mamaria es un órgano dinámico que alcanza su máximo desarrollo funcional con la lactancia, momento en el cual, a través de la producción de leche, aporta nutrientes y protección inmunológica a las crías de los mamíferos. Cuando la lactancia finaliza con el destete, el exceso de tejido glandular debe desaparecer y la glándula sufre una extensa remodelación hasta alcanzar nuevamente un estado pre-gestacional, preparada para un nuevo ciclo. La involución del tejido mamario es un proceso complejo durante el cual se suceden de forma coordinada una serie de eventos como la muerte de las células epiteliales secretoras, la proliferación de tejido adiposo circundante y la re…