scholarly journals ZnT4 provides zinc to zinc-dependent proteins in the trans-Golgi network critical for cell function and Zn export in mammary epithelial cells

2012 ◽  
Vol 303 (3) ◽  
pp. C291-C297 ◽  
Author(s):  
Nicholas H. McCormick ◽  
Shannon L. Kelleher
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Cell Membrane ◽  
Cell Function ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Milk Secretion ◽  
Trans Golgi Network ◽  
Dependent Protein ◽  
Golgi Network

Zinc (Zn) transporter 4 (ZnT4) plays a key role in mammary gland Zn metabolism. A mutation in ZnT4 ( SLC30A4) that targets the protein for degradation is responsible for the “lethal milk” ( lm/lm) mouse phenotype. ZnT4 protein is only detected in the secreting mammary gland, and lm/lm mice have ∼35% less Zn in milk, decreased mammary gland size, and decreased milk secretion. However, the precise contribution of ZnT4 is unknown. We used cultured mouse mammary epithelial cells (HC11) and determined that ZnT4 was localized to the trans-Golgi network (TGN) and cell membrane and transported Zn from the cytoplasm. ZnT4-mediated Zn import into the TGN directly contributed to labile Zn accumulation as ZnT4 overexpression increased FluoZin3 fluorescence. Moreover, ZnT4 provided Zn for metallation of galactosyltransferase, a Zn-dependent protein localized within the TGN that is critical for milk secretion, and carbonic anhydrase VI, a Zn-dependent protein secreted from the TGN into milk. We further noted that ZnT4 relocalized to the cell membrane in response to Zn. Together these studies demonstrated that ZnT4 transports Zn into the TGN, which is critical for key secretory functions of the mammary cell.

scholarly journals Allograft inflammatory factor-1 (AIF-1) induces inflammatory mediator production via NF-κB signaling and impairs bovine mammary epithelial cells via mitochondrial pathway

2020 ◽  
Author(s):  
Danru Yang ◽  
Yinghuan Wu ◽  
Yanying Zhao
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Cell Membrane ◽  
Cell Apoptosis ◽  
Mammary Epithelial Cells ◽  
Bovine Mastitis ◽  
Mammary Epithelial ◽  
Cell Membrane Permeability ◽  
Inflammatory Factor ◽  
Bovine Mammary Epithelial Cells

Abstract Background Bovine mastitis is the inflammatory response of the mammary gland with an utmost threat to the dairy industry worldwide. Cytokine networks fuel inflammation. The sensitive and subtle changes of the inflammatory cytokine network in healthy and mastitic bovine mammary gland may encourage the use of cytokines in the diagnosis and prognosis of bovine mastitis. Allograft inflammatory factor-1 (AIF-1) is a proinflammatory cytokine mainly secreted by immune cells and it plays a central role in the complex signaling network of inflammation activation. Therefore, we explored the possible role of bovine AIF-1 related to bovine mastitis in the present study. Results The average concentration of AIF-1 in milks suffering from mastitis was 2.5 fold of that in the healthy cows, while its value decreased in cows recovered from mastitis. Furthermore, recombinant bovine AIF-1 up-regulated TNF-α, IL-6, and monocyte chemoattractant protein 1 secretion from bovine mammary epithelial cells with NF-κB activating, then NF-κB signaling inhibitor BAY 11-7085 abolished the increase of these inflammatory cytokines secretion induced by AIF-1. Thereafter, AIF-1 impaired bovine mammary epithelial cell viability, induced cell membrane permeability and cell apoptosis with exacerbated nitric oxide and oxidative stress, activated caspase 3, decreased mitochondrial membrane potential and intracellular ATP concentration. Conclusion These results indicated that AIF-1 prompted inflammation mediator production of bovine mammary epithelial cells via NF-κB signaling. Moreover, it damaged epithelial cells by depressing cell viability, inducing cell membrane permeability and cell apoptosis, which might be related to bovine mastitis.

scholarly journals Evidence of Rab3A Expression, Regulation of Vesicle Trafficking, and Cellular Secretion in Response to Heregulin in Mammary Epithelial Cells

2000 ◽  
Vol 20 (23) ◽  
pp. 9092-9101 ◽  
Author(s):  
Ratna K. Vadlamudi ◽  
Rui-An Wang ◽  
Amjad H. Talukder ◽  
Liana Adam ◽  
Randy Johnson ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Vesicle Trafficking ◽  
Mammary Epithelial ◽  
Coated Vesicle ◽  
Human Breast ◽  
Breast Epithelial Cells ◽  
Breast Epithelial ◽  
Stimulation Of

ABSTRACT Heregulin β1 (HRG), a combinatorial ligand for human growth factor receptors 3 and 4, is a regulatory polypeptide that promotes the differentiation of mammary epithelial cells into secretory lobuloalveoli. Emerging evidence suggests that the processes of secretory pathways, such as biogenesis and trafficking of vesicles in neurons and adipose cells, are regulated by the Rab family of low-molecular-weight GTPases. In this study, we identified Rab3A as a gene product induced by HRG. Full-length Rab3A was cloned from a mammary gland cDNA library. We demonstrated that HRG stimulation of human breast cancer cells and normal breast epithelial cells induces the expression of Rab3A protein and mRNA in a cycloheximide-independent manner. HRG-mediated induction of Rab3A expression was blocked by an inhibitor of phosphatidylinositol 3-kinase but not by inhibitors of mitogen-activated protein kinases p38MAPK and p42/44MAPK. Human breast epithelial cells also express other components of regulated vesicular traffic, such as rabphilin 3A, Doc2, and syntaxin. Rab3A was predominantly localized in the cytosol, and HRG stimulation of the epithelial cells also raised the level of membrane-bound Rab3A. HRG treatment induced a profound alteration in the cell morphology in which cells displayed neuron-like membrane extensions that contained Rab3A-coated, vesicle-like structures. In addition, HRG also promoted the secretion of cellular proteins from the mammary epithelial cells. The ability of HRG to modify exocytosis was verified by using a growth hormone transient-transfection system. Analysis of mouse mammary gland development revealed the expression of Rab3A in mammary epithelial cells. Furthermore, expression of the HRG transgene in Harderian tumors in mice also enhanced the expression of Rab3A. These observations provide new evidence of the existence of a Rab3A pathway in mammary epithelial cells and suggest that it may play a role in vesicle trafficking and secretion of proteins from epithelial cells in response to stimulation by the HRG expressed within the mammary mesenchyma.

MicroRNA-432 inhibits milk fat synthesis by targeting SCD and LPL in ovine mammary epithelial cells

2021 ◽  
Author(s):  
Zhiyun Hao ◽  
Yuzhu Luo ◽  
Jiqing Wang ◽  
Jon Hickford ◽  
Huitong Zhou ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Milk Production ◽  
Milk Fat ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas ◽  
Fat Synthesis ◽  
Milk Fat Synthesis

In our previous studies, microRNA-432 (miR-432) was found to be one of differentially expressed miRNAs in ovine mammary gland between the two breeds of lactating sheep with different milk production...

Bovine mammary epithelial cells, initiators of innate immune responses to mastitis

2005 ◽  
Vol 45 (8) ◽  
pp. 757 ◽  
Author(s):  
C. Gray ◽  
Y. Strandberg ◽  
L. Donaldson ◽  
R. L. Tellam
Keyword(s):  
Immune Response ◽  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Vital Role ◽  
Mammary Epithelial ◽  
Innate Immune ◽  
Mammary Tissue ◽  
Effector Cells ◽  
Bovine Mammary Epithelial Cells

Innate immunity plays a vital role in the protection of the bovine mammary gland against mastitis. Until recently, the migration of effector cells such as neutrophils and monocytes into the mammary gland was thought to provide the only defence against invading pathogens. However, mammary epithelial cells may also play an important role in the immune response, contributing to the innate defence of the mammary tissue through secretion of antimicrobial peptides and attraction of circulating immune effector cells. This paper reviews the innate immune pathways in mammary epithelial cells and examines their role in the initiation of an innate immune response to Gram-positive and Gram-negative bacteria.

scholarly journals Chemerin Regulates Epithelial Barrier Function of Mammary Glands in Dairy Cows

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3194
Author(s):  
Yutaka Suzuki ◽  
Sachi Chiba ◽  
Koki Nishihara ◽  
Keiichi Nakajima ◽  
Akihiko Hagino ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Dairy Cows ◽  
Barrier Function ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Epithelial Barrier ◽  
Epithelial Tissue ◽  
Epithelial Barrier Function

Epithelial barrier function in the mammary gland acts as a forefront of the defense mechanism against mastitis, which is widespread and a major disorder in dairy production. Chemerin is a chemoattractant protein with potent antimicrobial ability, but its role in the mammary gland remains unelucidated. The aim of this study was to determine the function of chemerin in mammary epithelial tissue of dairy cows in lactation or dry-off periods. Mammary epithelial cells produced chemerin protein, and secreted chemerin was detected in milk samples. Chemerin treatment promoted the proliferation of cultured bovine mammary epithelial cells and protected the integrity of the epithelial cell layer from hydrogen peroxide (H2O2)-induced damage. Meanwhile, chemerin levels were higher in mammary tissue with mastitis. Tumor necrosis factor alpha (TNF-α) strongly upregulated the expression of the chemerin-coding gene (RARRES2) in mammary epithelial cells. Therefore, chemerin was suggested to support mammary epithelial cell growth and epithelial barrier function and to be regulated by inflammatory stimuli. Our results may indicate chemerin as a novel therapeutic target for diseases in the bovine mammary gland.

scholarly journals p19ARFDetermines the Balance between Normal Cell Proliferation Rate and Apoptosis during Mammary Gland Development

2004 ◽  
Vol 15 (5) ◽  
pp. 2302-2311 ◽  
Author(s):  
Yijun Yi ◽  
Anne Shepard ◽  
Frances Kittrell ◽  
Biserka Mulac-Jericevic ◽  
Daniel Medina ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mammary Gland ◽  
Epithelial Cells ◽  
Protein Level ◽  
Normal Cell ◽  
Mammary Gland Development ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Proliferation Rate ◽  
Gland Development

This study demonstrated, for the first time, the following events related to p19ARFinvolvement in mammary gland development: 1) Progesterone appears to regulate p19ARFin normal mammary gland during pregnancy. 2) p19ARFexpression levels increased sixfold during pregnancy, and the protein level plateaus during lactation. 3) During involution, p19ARFprotein level remained at high levels at 2 and 8 days of involution and then, declined sharply at day 15. Absence of p19ARFin mammary epithelial cells leads to two major changes, 1) a delay in the early phase of involution concomitant with downregulation of p21Cip1and decrease in apoptosis, and 2) p19ARFnull cells are immortal in vivo measured by serial transplantion, which is partly attributed to complete absence of p21Cip1compared with WT cells. Although, p19ARFis dispensable in mammary alveologenesis, as evidenced by normal differentiation in the mammary gland of pregnant p19ARFnull mice, the upregulation of p19ARFby progesterone in the WT cells and the weakness of p21Cip1in mammary epithelial cells lacking p19ARFstrongly suggest that the functional role(s) of p19ARFin mammary gland development is critical to sustain normal cell proliferation rate during pregnancy and normal apoptosis in involution possibly through the p53-dependent pathway.

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