Remodeling of Zn2+ homeostasis upon differentiation of mammary epithelial cells

Han, Yu; Sanford, Lynn; Simpson, David; Dowell, Robin D.; Palmer, Amy E.

doi:10.1039/c9mt00301k

Cited by 8 publications

(9 citation statements)

References 66 publications

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“…Zn 2+ has a protective effect on renal ischemia-reperfusion injury by augmenting superoxide dismutase activity and lowering the Bax/Bcl-2 expression ratio to reduce apoptosis [37]. Therefore, our results support that ZnO-NP, at sub-lethal dosage, causes a mild elevation of [Zn 2+ ] i which has been shown to enhance the expression of metallothioneins [46] and the activity of Zn 2+ -related superoxide dismutase [47]. Both metallothioneins and dismutase can lower the ROS level leading to the down-regulation of the expression of p53 and Bax/Bcl-2 ratio [47,48].…”

Section: Plos Onesupporting

confidence: 74%

Zinc oxide nanoparticles modulate the gene expression of ZnT1 and ZIP8 to manipulate zinc homeostasis and stress-induced cytotoxicity in human neuroblastoma SH-SY5Y cells

Pan¹,

Lin²,

Kao³

et al. 2020

PLoS ONE

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Zinc ions (Zn 2+) are important messenger molecules involved in various physiological functions. To maintain the homeostasis of cytosolic Zn 2+ concentration ([Zn 2+ ] c), Zrt/Irt-related proteins (ZIPs) and Zn 2+ transporters (ZnTs) are the two families of proteins responsible for decreasing and increasing the [Zn 2+ ] c , respectively, by fluxing Zn 2+ across the membranes of the cell and intracellular compartments in opposite directions. Most studies focus on the cytotoxicity incurred by a high concentration of [Zn 2+ ] c and less investigate the [Zn 2+ ] c at physiological levels. Zinc oxide-nanoparticle (ZnO-NP) is blood brain barrier-permeable and elevates the [Zn 2+ ] c to different levels according to the concentrations of ZnO-NP applied. In this study, we mildly elevated the [Zn 2+ ] c by ZnO-NP at concentrations below 1 μg/ml, which had little cytotoxicity, in cultured human neuroblastoma SH-SY5Y cells and characterized the importance of Zn 2+ transporters in 6-hydroxy dopamine (6-OHDA)-induced cell death. The results show that ZnO-NP at low concentrations elevated the [Zn 2+ ] c transiently in 6 hr, then declined gradually to a basal level in 24 hr. Knocking down the expression levels of ZnT 1 (located mostly at the plasma membrane) and ZIP 8 (present in endosomes and lysosomes) increased and decreased the ZnO-NP-induced elevation of [Zn 2+ ] c , respectively. ZnO-NP treatment reduced the basal levels of reactive oxygen species and Bax/Bcl-2 mRNA ratios; in addition, ZnO-NP decreased the 6-OHDA-induced ROS production, p53 expression, and cell death. These results show that ZnO-NP-induced mild elevation in [Zn 2 + ] c activates beneficial effects in reducing the 6-OHDA-induced cytotoxic effects. Therefore, brain-delivery of ZnO-NP can be regarded as a potential therapy for neurodegenerative diseases.

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Section: Plos Onesupporting

confidence: 74%

Zinc oxide nanoparticles modulate the gene expression of ZnT1 and ZIP8 to manipulate zinc homeostasis and stress-induced cytotoxicity in human neuroblastoma SH-SY5Y cells

Pan¹,

Lin²,

Kao³

et al. 2020

PLoS ONE

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“… 10 , 11 How zinc is managed in biological systems is not yet well understood, and studies following zinc homeostasis and dynamics in cells are ongoing. 12 − 14 Additionally, protein design based on Zn 2+ binding sites is used to introduce or alter catalytic activity. 3 , 4 …”

Section: Introductionmentioning

confidence: 99%

Probing a Silent Metal: A Combined X-ray Absorption and Emission Spectroscopic Study of Biologically Relevant Zinc Complexes

et al. 2020

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As the second most common transition metal in the human body, zinc is of great interest to research but has few viable routes for its direct structural study in biological systems. Herein, Zn valence-to-core X-ray emission spectroscopy (VtC XES) and Zn K-edge X-ray absorption spectroscopy (XAS) are presented as a means to understand the local structure of zinc in biological systems through the application of these methods to a series of biologically relevant molecular model complexes. Taken together, the Zn K-edge XAS and VtC XES provide a means to establish the ligand identity, local geometry, and metal–ligand bond lengths. Experimental results are supported by correlation with density-functional-theory-based calculations. Combining these theoretical and experimental approaches will enable future applications to protein systems in a predictive manner.

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“…75 The Zn + is essential for the expression of milk proteins during the terminal differentiation of MECs. 76 The Rab proteins are GTPases involved in the transport of proteins between different intracellular compartments. The protein Rab5b mediates the internalization of prolactin and phosphorylation of STAT5 molecules, 77 which induces milk protein genes' expression during the terminal differentiation of MECs.…”

Section: Discussionmentioning

confidence: 99%

“…CZIB has two conserved CXXC domains and have a role in zinc (Zn) binding 75 . The Zn + is essential for the expression of milk proteins during the terminal differentiation of MECs 76 …”

Section: Discussionmentioning

confidence: 99%

TMT based deep proteome analysis of buffalo mammary epithelial cells and identification of novel protein signatures during lactogenic differentiation

et al. 2021

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The lactating mammary gland harbours numerous matured alveoli with their lumen surrounded by differentiated mammary epithelial cells (MECs), which are exclusively involved in milk synthesis and secretion. Buffalo (Bubalus bubalis) is the second major milk-producing animal, and its physiology is different from cattle. The complete protein machinery involved in MECs differentiation is still not defined in ruminants, in particular, buffalo. Therefore, we have studied the differential expression of regulated proteins in the in vitro grown buffalo MECs (BuMECs) at different time points (on 3, 6, 12, and 15 days) of their differentiation in the presence of lactogenic hormones. TMT-based MS analysis identified 4,934 proteins; of them, 681 were differentially expressed proteins (DEPs). The principal component analysis suggested a highly heterogeneous expression of DEPs at the four-time points of hormone treatment, with most of them (307) attained the highest expression on 12 days. Bioinformatics analysis revealed the association of DEPs with 24 KEGG pathways.We observed few new proteins, namely ABCA13, IVL, VPS37, CZIB, RFX7, Rab5, TTLL12, SMEK1, GDI2, and TMEM131 in BuMECs. The function of one of the highly upregulated proteins, namely involucrin in the differentiation of BuMECs was confirmed based on biochemical inhibition assay. The results further conclude that the proteins with higher abundance can be considered as the potential biomarkers for differentiation, and they may have a significant association with the lactation process 2 of 22 | JASWAL et AL.

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Remodeling of Zn2+ homeostasis upon differentiation of mammary epithelial cells

Abstract: Zinc is the second most abundant transition metal in humans and an essential nutrient required for growth and development of newborns.

Cited by 8 publications

References 66 publications

Zinc oxide nanoparticles modulate the gene expression of ZnT1 and ZIP8 to manipulate zinc homeostasis and stress-induced cytotoxicity in human neuroblastoma SH-SY5Y cells

Zinc oxide nanoparticles modulate the gene expression of ZnT1 and ZIP8 to manipulate zinc homeostasis and stress-induced cytotoxicity in human neuroblastoma SH-SY5Y cells

Probing a Silent Metal: A Combined X-ray Absorption and Emission Spectroscopic Study of Biologically Relevant Zinc Complexes

TMT based deep proteome analysis of buffalo mammary epithelial cells and identification of novel protein signatures during lactogenic differentiation

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