Remodeling of Zn2+ Homeostasis Upon Differentiation of Mammary Epithelial Cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA602910 | ENA |
REPOSITORIES: ENA
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Project description:Using mouse mammary epithelial cells as a model system, we investigated the remodeling of zinc homeostasis during differentiation induced by treatment with the lactogenic hormones cortisol and prolactin. RNA-Seq at different stages of differentiation revealed changes in global gene expression, including genes encoding zinc-dependent proteins and regulators of zinc homeostasis. Increases in mRNA levels of three zinc homeostasis genes,.
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Project description:Baroreflex control of cardiac contraction (positive inotropy) through sympathetic nerve activation is important to maintain cardiocirculatory homeostasis. Transient receptor potential canonical subfamily (TRPC) channels are responsible for alfa1-adrenoceptor (alfa1AR)-stimulated cation entry and their upregulation is reportedly associated with pathological cardiac remodeling, but whether TRPC channels participate in physiological pump functions remains unclear. Here, we demonstrate that TRPC6-specific Zn2+ influx potentiates alfa-adrenoceptor (alfaAR)-stimulated positive inotropy in rodent cardiomyocytes. Deletion of the trpc6 gene impairs sympathetic nerve-activated positive inotropy, but not chronotropy in mice. TRPC6-mediated Zn2+ influx boosts alfa1AR-stimulatedalfaAR/Gs-dependent signaling in rat cardiomyocytes by inhibiting alfa-arrestin-mediated alfaAR internalization. Replacing two TRPC6-specific amino acids in the pore region with those of TRPC3 diminishes the alfa1AR-stimulated Zn2+ influx and positive inotropic response. Pharmacological enhancement of TRPC6-mediated Zn2+ influx prevents the progression of heart failure in dilated cardiomyopathy mice. Our data provide evidence that TRPC6-mediated Zn2+ influx with α1AR stimulation enhances baroreflex-induced positive inotropy, which may be a new therapeutic strategy for chronic heart failure.
2022-09-14 | GSE189494 | GEO
Project description:Zinc (Zn2+) is an integral component of many proteins and has been shown to act in a regulatory capacity in different mammalian systems, including as a neurotransmitter in neurons throughout the brain. While Zn2+ plays an important role in modulating neuronal potentiation and synaptic plasticity, little is known about the signaling mechanisms of this regulation. In dissociated rat hippocampal neuron cultures, we used fluorescent Zn2+ sensors to rigorously define resting Zn2+ levels and stimulation-dependent intracellular Zn2+ dynamics, and we performed RNA-Seq to characterize Zn2+-dependent transcriptional effects upon stimulation. We found that relatively small changes in cytosolic Zn2+ during stimulation altered expression levels of 931 genes, and these Zn2+ dynamics induced transcription of many genes implicated in neurite expansion and synaptic growth. Additionally, while we were unable to verify the presence of synaptic Zn2+ in these cultures, we did detect the synaptic vesicle Zn2+ transporter ZnT3 and found it to be substantially upregulated by cytosolic Zn2+ increases. These results provide the first global sequencing-based examination of Zn2+-dependent changes in transcription and identify genes that may mediate Zn2+-dependent processes and functions.
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2020-05-31 | GSE148207 | GEO
Project description:Zinc (Zn2+) is an important trace metal ion that has been shown to regulate the expression of several (virulence) genes in streptococci. Previously, we analyzed the genome-wide response of S. pneumoniae to Zn2+-stress. In this work, we have performed a transcriptomic analysis to identify genes that are differentially expressed under intracellular Zn2+-limitation. This revealed a number of genes that are highly upregulated in the absence of extracellular Zn2+, amongst which the genes belonging to the regulon of the Zn2+-responsive repressor AdcR, like adcBCA, encoding a Zn2+-dependent ABC-uptake system, adcAII, encoding a Zn2+-binding lipoprotein, and also virulence genes belonging to the Pht family (phtA, phtB, phtD and phtE). Using transcriptome analysis, lacZ-reporter studies, in vitro DNA binding experiments, and in silico operator predictions, we show that AdcR directly represses the promoters of adcRCBA, adcAII-phtD, phtA, phtB and phtE in the presence of Zn2+. AdcR can also function as an activator, since in the presence of Zn2+ it directly induces expression of adh that encodes a Zn2+-containing alcohol dehydrogenase. In conclusion, the genome-wide transcriptional response of S. pneumoniae to Zn2+-limitation was established, which is mainly mediated via direct regulation by the Zn2+-dependent regulator AdcR. This SuperSeries is composed of the SubSeries listed below.
2011-05-13 | GSE29236 | GEO
Project description:Zinc (Zn2+) is an important trace metal ion that has been shown to regulate the expression of several (virulence) genes in streptococci. Previously, we analyzed the genome-wide response of S. pneumoniae to Zn2+-stress. In this work, we have performed a transcriptomic analysis to identify genes that are differentially expressed under intracellular Zn2+-limitation. This revealed a number of genes that are highly upregulated in the absence of extracellular Zn2+, amongst which the genes belonging to the regulon of the Zn2+-responsive repressor AdcR, like adcBCA, encoding a Zn2+-dependent ABC-uptake system, adcAII, encoding a Zn2+-binding lipoprotein, and also virulence genes belonging to the Pht family (phtA, phtB, phtD and phtE). Using transcriptome analysis, lacZ-reporter studies, in vitro DNA binding experiments, and in silico operator predictions, we show that AdcR directly represses the promoters of adcRCBA, adcAII-phtD, phtA, phtB and phtE in the presence of Zn2+. AdcR can also function as an activator, since in the presence of Zn2+ it directly induces expression of adh that encodes a Zn2+-containing alcohol dehydrogenase. In conclusion, the genome-wide transcriptional response of S. pneumoniae to Zn2+-limitation was established, which is mainly mediated via direct regulation by the Zn2+-dependent regulator AdcR. Two condition design comparison of Wild-type strain including a dye swap Refer to individual Series. This SuperSeries is composed of the following subset Series: GSE29234: adcR mutant vs wild type D39 GSE29235: Low Zn vs high Zn in CDM
2011-05-13 | E-GEOD-29236 | biostudies-arrayexpress
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2019-02-15 | PXD006535 | Pride
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| PRJNA670937 | ENA
Project description:Peterson2010 - integrated calcium homeostasis
and bone remodelling
This model is described in the article:
A physiologically based
mathematical model of integrated calcium homeostasis and bone
remodeling.
Peterson MC, Riggs MM.
Bone 2010 Jan; 46(1): 49-63
Abstract:
Bone biology is physiologically complex and intimately
linked to calcium homeostasis. The literature provides a wealth
of qualitative and/or quantitative descriptions of cellular
mechanisms, bone dynamics, associated organ dynamics, related
disease sequela, and results of therapeutic interventions. We
present a physiologically based mathematical model of
integrated calcium homeostasis and bone biology constructed
from literature data. The model includes relevant cellular
aspects with major controlling mechanisms for bone remodeling
and calcium homeostasis and appropriately describes a broad
range of clinical and therapeutic conditions. These include
changes in plasma parathyroid hormone (PTH), calcitriol,
calcium and phosphate (PO4), and bone-remodeling markers as
manifested by hypoparathyroidism and hyperparathyroidism, renal
insufficiency, daily PTH 1-34 administration, and receptor
activator of NF-kappaB ligand (RANKL) inhibition. This model
highlights the utility of systems approaches to physiologic
modeling in the bone field. The presented bone and calcium
homeostasis model provides an integrated mathematical construct
to conduct hypothesis testing of influential system aspects, to
visualize elements of this complex endocrine system, and to
continue to build upon iteratively with the results of ongoing
scientific research.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000613.
To cite BioModels Database, please use:
BioModels Database:
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To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
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Public Domain Dedication for more information.
2020-03-04 | BIOMD0000000613 | BioModels