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

2014 ◽  
Vol 459 (2) ◽  
pp. 355-368 ◽  
Author(s):  
Teresa Arnandis ◽  
Ivan Ferrer-Vicens ◽  
Luis Torres ◽  
Concha García ◽  
Elena R. Garcia-Trevijano ◽  
...  

The results of the present study unveil novel and important nuclear functions of calpains in tissue remodelling. Although inducing nuclear permeability during programmed cell death, histone H3 is identified as a new target of calpain-1 upon adipocyte differentiation.

Development ◽  
2011 ◽  
Vol 139 (2) ◽  
pp. 269-275 ◽  
Author(s):  
J. O'Brien ◽  
H. Martinson ◽  
C. Durand-Rougely ◽  
P. Schedin

2012 ◽  
Vol 19 (9) ◽  
pp. 1536-1548 ◽  
Author(s):  
T Arnandis ◽  
I Ferrer-Vicens ◽  
E R García-Trevijano ◽  
V J Miralles ◽  
C García ◽  
...  

2001 ◽  
Vol 152 (4) ◽  
pp. 693-703 ◽  
Author(s):  
Caroline M. Alexander ◽  
Sushma Selvarajan ◽  
John Mudgett ◽  
Zena Werb

The matrix metalloproteinase MMP-3/stromelysin-1 (Str1) is highly expressed during mammary gland involution induced by weaning. During involution, programmed cell death of the secretory epithelium takes place concomitant with the repopulation of the mammary fat pad with adipocytes. In this study, we have used a genetic approach to determine the role of Str1 during mammary involution. Although Str1 has been shown to induce unscheduled apoptosis when expressed ectopically during late pregnancy (Alexander, C.M., E.W. Howard, M.J. Bissell, and Z. Werb. 1996. J. Cell Biol. 135:1669–1677), we found that during post-lactational involution, mammary glands from transgenic mice that overexpress the tissue inhibitor of metalloproteinases, TIMP-1 (TO), or mice carrying a targeted mutation in Str1 showed accelerated differentiation and hypertrophy of adipocytes, while epithelial apoptosis was unaffected. These data suggest that matrix metalloproteinases (MMPs) do not induce unscheduled epithelial cell death after weaning, but instead alter the stromal microenvironment. We used adipogenic 3T3-L1 cells as a cell culture model to test the function of MMPs during adipocyte differentiation. Fibroblastic 3T3-L1 progenitor cells expressed very low levels of MMPs or TIMPs. The transcription of a number of MMP and TIMP mRNAs [Str1, MT1-MMP, (MMP-14) collagenase-3 (MMP-13), gelatinase A (MMP-2), and TIMP-1, -2 and -3] was induced in committed preadipocytes, but only differentiated adipocytes expressed an activated MMP, gelatinase A. The addition of MMP inhibitors (GM 6001 and TIMP-1) dramatically accelerated the accumulation of lipid during differentiation. We conclude that MMPs, especially Str1, determine the rate of adipocyte differentiation during involutive mammary gland remodeling.


Development ◽  
1992 ◽  
Vol 115 (1) ◽  
pp. 49-58 ◽  
Author(s):  
R. Strange ◽  
F. Li ◽  
S. Saurer ◽  
A. Burkhardt ◽  
R.R. Friis

During post-lactational mammary gland involution, the bulk of mammary epithelium dies and is reabsorbed. This massive cell death and tissue restructuring was found to be accompanied by a specific pattern of gene expression. Northern blot analysis showed that weaning resulted in a dramatic drop in ODC, a gene involved in synthesis of a component of milk, and the nearly simultaneous induction of SGP-2, a gene associated with apoptotic cell death. These changes were followed by decreases in expression of milk protein genes to basal levels and expression of genes associated with regulation of cell proliferation and differentiation, p53, c-myc and TGF-beta 1. Subsequently, additional genes implicated in stress response, tissue remodelling, and apoptotic cell death were transiently expressed, expression peaking at about 6 days post-weaning. A non-random degradation of DNA yielding the oligonucleosomal length fragmentation pattern typical of apoptotic cell death (Wyllie, 1980; Wyllie et al., 1980) was detected in association with morphological changes and gene expression. The correlations between: (a) changes in morphology, (b) pattern of gene expression and (c) changes in DNA integrity suggest that complementary programs for cell death and tissue remodelling direct post-lactational mammary gland involution.


Author(s):  
Robert Strange ◽  
Robert R. Friis ◽  
Lynne T. Bemis ◽  
F. Jon Geske

1997 ◽  
Vol 94 (7) ◽  
pp. 3425-3430 ◽  
Author(s):  
M. Li ◽  
X. Liu ◽  
G. Robinson ◽  
U. Bar-Peled ◽  
K.-U. Wagner ◽  
...  

2021 ◽  
Vol 22 (3) ◽  
pp. 1215
Author(s):  
Mi Ho Jeong ◽  
Mi Seon Jeon ◽  
Ga Eun Kim ◽  
Ha Ryong Kim

Airway epithelial cell death contributes to the pathogenesis of lung fibrosis. Polyhexamethylene guanidine phosphate (PHMG-p), commonly used as a disinfectant, has been shown to be strongly associated with lung fibrosis in epidemiological and toxicological studies. However, the molecular mechanism underlying PHMG-p-induced epithelial cell death is currently unclear. We synthesized a PHMG-p–fluorescein isothiocyanate (FITC) conjugate and assessed its uptake into lung epithelial A549 cells. To examine intracellular localization, the cells were treated with PHMG-p–FITC; then, the cytoplasmic organelles were counterstained and observed with confocal microscopy. Additionally, the organelle-specific cell death pathway was investigated in cells treated with PHMG-p. PHMG-p–FITC co-localized with the endoplasmic reticulum (ER), and PHMG-p induced ER stress in A549 cells and mice. The ER stress inhibitor tauroursodeoxycholic acid (TUDCA) was used as a pre-treatment to verify the role of ER stress in PHMG-p-induced cytotoxicity. The cells treated with PHMG-p showed apoptosis, which was inhibited by TUDCA. Our results indicate that PHMG-p is rapidly located in the ER and causes ER-stress-mediated apoptosis, which is an initial step in PHMG-p-induced lung fibrosis.


2016 ◽  
Vol 54 (5) ◽  
pp. 697-706 ◽  
Author(s):  
Haranatha R. Potteti ◽  
Subbiah Rajasekaran ◽  
Senthilkumar B. Rajamohan ◽  
Chandramohan R. Tamatam ◽  
Narsa M. Reddy ◽  
...  

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