Calcium transport by mammary secretory cells: Mechanisms underlying transepithelial movement

Shennan, D.B.

doi:10.2478/s11658-008-0020-y

Cited by 12 publications

(12 citation statements)

References 37 publications

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“…In addition to ER, other organelles also have a role in [Ca 2+ ] i homeostasis of the cell, and they include the mitochondrial Ca 2+ uniporter (MCU) and the Na + /Ca 2+ exchanger (NCX) of the secretory pathway Ca 2+ /Mn 2+ ATPases (SPCAs) of the Golgi [27][28][29]41]. Although the Golgi does not seem to be a place for Ca 2+ storage, it has a critical role in the intracellular vesicular trafficking and secretion of proteins together with ER and Ca 2+ [42]. It has been suggested that an increase of [Ca 2+ ] i may increase the secretion flow, which is a primary Golgi function and responsible for executing net unidirectional intracellular transport from the rough ER (RER) toward lysosomes and the cell surface [43].…”

Section: Regulatory Roles Of Ca 2+ In Cellular Functionsmentioning

confidence: 99%

Ca2+ Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis

Tajbakhsh

Kovanen

Rezaee

et al. 2019

JCM

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In atherosclerosis, macrophages in the arterial wall ingest plasma lipoprotein-derived lipids and become lipid-filled foam cells with a limited lifespan. Thus, efficient removal of apoptotic foam cells by efferocytic macrophages is vital to preventing the dying foam cells from forming a large necrotic lipid core, which, otherwise, would render the atherosclerotic plaque vulnerable to rupture and would cause clinical complications. Ca 2+ plays a role in macrophage migration, survival, and foam cell generation. Importantly, in efferocytic macrophages, Ca 2+ induces actin polymerization, thereby promoting the formation of a phagocytic cup necessary for efferocytosis. Moreover, in the efferocytic macrophages, Ca 2+ enhances the secretion of anti-inflammatory cytokines. Various Ca 2+ antagonists have been seminal for the demonstration of the role of Ca 2+ in the multiple steps of efferocytosis by macrophages. Moreover, in vitro and in vivo experiments and clinical investigations have revealed the capability of Ca 2+ antagonists in attenuating the development of atherosclerotic plaques by interfering with the deposition of lipids in macrophages and by reducing plaque calcification. However, the regulation of cellular Ca 2+ fluxes in the processes of efferocytic clearance of apoptotic foam cells and in the extracellular calcification in atherosclerosis remains unknown. Here, we attempted to unravel the molecular links between Ca 2+ and efferocytosis in atherosclerosis and to evaluate cellular Ca 2+ fluxes as potential treatment targets in atherosclerotic cardiovascular diseases.

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Section: Regulatory Roles Of Ca 2+ In Cellular Functionsmentioning

confidence: 99%

Ca2+ Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis

Tajbakhsh

Kovanen

Rezaee

et al. 2019

JCM

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“…Calcium also acts as a second messenger in the GPCR signal transduction, which mediates downstream pathways. Although the transport of calcium in mammary epithelial cells has previously been studied (3,70), and the mechanisms underlying calcium transport in the lactating mammary gland are elucidated, the level of ionized calcium and its regulation in cytosol remain unclear (59). One of the G1 genes in the calcium signaling pathway, ryanodine receptor 3 (Ryr3) is an intracellular calcium release channel.…”

Section: Discussionmentioning

confidence: 99%

Identification of gene sets and pathways associated with lactation performance in mice

Wei

Ramanathan

Martin

et al. 2013

Physiological Genomics

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-Mammary transcriptome analyses across the lactation cycle and transgenic animal studies have identified candidate genes for mammogenesis, lactogenesis and involution; however, there is a lack of information on pathways that contribute to lactation performance. Previously we have shown significant differences in lactation performance, mammary gland histology, and gene expression profiles during lactation [lactation day 9 (L9)] between CBA/CaH (CBA) and the superior performing QSi5 strains of mice. In the present study, we compared these strains at midpregnancy [pregnancy day 12 (P12)] and utilized these data along with data from a 14th generation of intercross (AIL) to develop an integrative analysis of lactation performance. Additional analysis by quantitative reverse transcription PCR examined the correlation between expression profiles of lactation candidate genes and lactation performance across six inbred strains of mice. The analysis demonstrated that the mammary epithelial content per unit area was similar between CBA and QSi5 mice at P12, while differential expression was detected in 354 mammary genes (false discovery rate Ͻ 0.1). Gene ontology and functional annotation analyses showed that functional annotation terms associated with cell division and proliferation were the most enriched in the differentially expressed genes between these two strains at P12. Further analysis revealed that genes associated with neuroactive ligand-receptor interaction and calcium signaling pathways were significantly upregulated and positively correlated with lactation performance, while genes associated with cell cycle and DNA replication pathways were downregulated and positively correlated with lactation performance. There was also a significant negative correlation between Grb10 expression and lactation performance. In summary, using an integrative genomic approach we have identified key genes and pathways associated with lactation performance. gene sets; lactation performance; mammary transcriptome; microarray; qRT-PCR LACTATION IS A COMPLEX PROCESS involving biosynthesis, secretory activation, and metabolic regulation. However, compared with the physiological events of mammary (alveolar) development, secretory differentiation during pregnancy, secretory activation at parturition, and involution (48, 56), genetically determined variation in lactation performance can be relatively subtle, and thus genetic variation in expression of the key genes for regulating milk production can be difficult to detect. A strategy employing inbred mouse strains to identify candidate genes and pathways associated with lactation performance has been developed in our laboratory (52). Comparison of gene expression profiles of lactating mammary glands between the highperformance QSi5 strain and the relatively low-performance

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“…The morphology and function of mammary glands undergo adaptive changes during pregnancy and lactation under the influence of several hormones, such as insulin, glucocorticoids, growth hormone and PRL, the latter of which regulates milk production and secretion, in part, by enhancing cellular uptake of nutrient molecules and transport of various ions across the mammary epithelia (Rillema et al, 2000; Neville et al, 2002). Ca 2+ , as a major constituent of milk, is largely transported from plasma to acinar lumen via the transcellular pathway, preferentially via PMCA2 located on the apical membrane (Shennan and Peaker, 2000; VanHouten et al, 2007; Shennan, 2008). Although the mechanism of Ca 2+ uptake across the basolateral membrane is not completely understood, several investigators suggested that it was mediated by channels of the TRPC family (El Hiani et al, 2006; Guilbert et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that mammary epithelial cells were able to extract a large amount of Ca 2+ from plasma to produce milk with Ca 2+ concentrations of ∼60 and ∼100 mM in rats and rabbits respectively (Shennan and Peaker, 2000; Neville, 2005; Shennan, 2008). Ca 2+ is transported into milk through the transcellular pathway by a three‐step process consisting of (i) Ca 2+ uptake at the blood‐facing (basolateral) membrane, presumably involving Ca 2+ ‐permeable TRPC (canonical transient receptor potential) channels (Nilius et al, 2007; Guilbert et al, 2008; Abramowitz and Birnbaumer, 2009); (ii) translocation of Ca 2+ from the cytoplasm into the Golgi apparatus by SPCAs (secretory pathway Ca 2+ ‐ATPases); and (iii) ATP‐dependent Ca 2+ extrusion at the apical (luminal) membrane via PMCA2 (plasma membrane Ca 2+ ‐ATPase isoform 2) (Shennan and Peaker, 2000; VanHouten et al, 2007; Shennan, 2008). However, expression profiles of such calcium transporters, particularly TRPC channels, in mammary tissues during lactation are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome analysis of mammary tissues reveals complex patterns of transporter gene expression during pregnancy and lactation

Anantamongkol

Charoenphandhu

Wongdee

et al. 2010

Cell Biology International

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As a complex Ca2+-rich fluid mixture of water, casein, lactose and several ions, milk secretion requires a number of unknown transporters, which can be identified by a genome-wide microarray study in mammary tissues of lactating animals. Ca2+ was reported to be secreted across mammary epithelial cells through the transcellular pathway, presumably involving TRPC (canonical transient receptor potential) channels. In the present study, we have used quantitative real-time PCR to demonstrate that the human mammary cell line MCF-7, as well as rat mammary tissues from pregnant and lactating rats, expressed TRPC1, TRPC5 and TRPC6. Expression of TRPC1, TRPC5 and TRPC7 were markedly up-regulated, whereas that of TRPC3 and TRPC4 was down-regulated in the early lactating period. To further identify other transporter genes affected by lactation, a highly sensitive Illumina microarray featuring Bead Array technology was performed on RNA samples from mammary tissues of lactating rats. We found that, of the 384 transcripts changed during lactation, 31 transcripts were involved in the transport of water and electrolytes, such as Ca2+, Na+, K+, Cl-, I-, Fe2+, sulfate and phosphate. The present study, therefore, provides information for further investigation of the mechanism of lactation-induced transport adaptation in mammary epithelial cells.

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Calcium transport by mammary secretory cells: Mechanisms underlying transepithelial movement

Cited by 12 publications

References 37 publications

Ca2+ Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis

Ca2+ Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis

Identification of gene sets and pathways associated with lactation performance in mice

Transcriptome analysis of mammary tissues reveals complex patterns of transporter gene expression during pregnancy and lactation

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