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At least 163 records · Page 9Linked to original sources
PubMed2004

L-Glutamate in the extracellular space regulates endogenous D-aspartate homeostasis in rat pheochromocytoma MPT1 cells.

In previous studies [FEBS Lett. 434 (1998) 231, Arch. Biochem. Biophys. 404 (2002) 92], we demonstrated for the first time that D-aspartate (D-Asp) is synthesized in cultured mammalian cell lines, such as pheochromocytoma 12 (PC12) and its subclone, MPT1. Our current focus is analysis of the dynamics of D-Asp homeostasis in these cells. In this communication, we show that L-glutamate (Glu) and L-Glu transporter substrates in the extracellular space regulate the homeostasis of endogenous D-Asp in MPT1 cells. D-Asp is apparently in dynamic homeostasis, whereby endogenous D-Asp is constantly released into the extracellular space by an undefined mechanism, and continuously and intensively taken up into cells by an L-Glu transporter. Under these conditions, L-Glu and its transporter substrates in the medium may competitively inhibit the uptake of D-Asp via the transporter, resulting in accumulation of the amino acid in the extracellular space. We additionally demonstrate that DL-TBOA, a well-established L-Glu transporter inhibitor, is taken up by the transporter during long time intervals, but not on a short time-scale.

Amino Acid Transport System X-AG↗
PubMed2004

Usefulness of insulin resistance measured by homeostasis model assessment in predicting restenosis after coronary stent placement in nondiabetic patients.

The homeostasis model assessment enabled us to evaluate insulin resistance easily and accurately in the clinical setting. The restenosis rate of coronary stenting was significantly higher among patients with high values for the homeostasis model assessment. Our findings suggest that insulin resistance measured by the homeostasis model assessment predicts restenosis after coronary stent placement in nondiabetic patients.

Aged↗
PubMed2006

Copper homeostasis in eukaryotes: teetering on a tightrope.

The transition metal copper is an essential trace element for both prokaryotes and eukaryotes. However, intracellular free copper has to be strictly limited due to its toxic side effects, not least the generation of reactive oxygen species (ROS) via redox cycling. Thus, all organisms have sophisticated copper homeostasis mechanisms that regulate uptake, distribution, sequestration and export of copper. From insects to mammals, metal-responsive transcription factor (MTF-1), a zinc finger transcription factor, controls expression of metallothioneins and other components involved in heavy metal homeostasis. In the fruit fly Drosophila, MTF-1 paradoxically acts as an activator under both high and low copper concentrations. Namely, under high copper conditions, MTF-1 activates metallothioneins in order to protect the cell, while under low copper conditions MTF-1 activates the copper importer Ctr1B in order to acquire scarce copper from the surroundings. This review highlights the current knowledge of copper homeostasis in eukaryotes with a focus on Drosophila and the role of MTF-1.

Animals↗
PubMed2006

Individual differences in glucose homeostasis: do our early life interactions with bacteria matter?

Exposure to endotoxin during the neonatal period in the rat has been shown to alter the development of the hypothalamic-pituitary-adrenal axis, inducing hyper-responsivity and increased glucocorticoid production in later-life. Glucocorticoids are known to have major metabolic effects, therefore, early life endotoxin exposure may have potentially serious consequences for metabolic homeostasis in the exposed animal. The aims of this study were therefore to assess the effect of neonatal bacterial endotoxin exposure on subsequent glucose homeostasis, insulin action and corticosterone production from puberty through to senescence. Male Fischer-344 rat pups were treated with bacterial endotoxin (0.05 mg/kg Salmonella enteritidis i.p.) or vehicle (sterile pyrogen free saline) on days 3 and 5 postnatally. Insulin and glucose levels were assessed before and during and intraperitoneal glucose tolerance test (IPGTT) together with body mass on postnatal days 40, 80, and 400. In addition, circulating levels of corticosterone were measured at 0, 30, and 90 min following a 30-min restraint challenge at these ages. Neonatal endotoxin challenge did not alter fasting plasma glucose or insulin, but impaired glucose tolerance at puberty (p<.05), improved glucose tolerance in adulthood (p<.05) and had no effect at senescence. During the IPGTT insulin was reduced at all ages (p<.05) following neonatal endotoxin challenge, but insulin sensitivity was unaltered, except for an increase in adulthood (p<.05), which is consistent with the observed improvement in glucose tolerance at this age. Neonatal endotoxin challenge reduced body mass during puberty and senescence (p<.05) but did not alter basal or stressed plasma corticosterone levels at any of the three developmental time points examined. These findings suggest that variations in an individual's early life bacterial environment may contribute to differences in glucose homeostasis, insulin action and disease susceptibility later in life.

Aging↗
PubMed2006

Calcium homeostasis in trigeminal ganglion cell bodies.

In primary sensory afferent neurons, Ca2+ plays a vital role in the regulation of cellular processes including receptor and synaptic plasticity, neurotransmitter and trophic factor release and gene regulation. Current understanding of the mechanisms underlying Ca2+ homeostasis of primary sensory afferent neurons is mostly derived from studies on dorsal root ganglia and nodose ganglia neuron cell bodies. Little is known about Ca2+ homeostasis in trigeminal ganglion neurons (TGNs). To determine what cellular processes contribute to electrically-evoked Ca2+ transients in TGNs, we probed Ca2+ regulatory mechanisms in TGN cell bodies from the ophthalmic division with a panel of pharmacological reagents. Ca2+ transients were evoked in fura-2 loaded TGNs by depolarizing the plasma membrane with brief (500 ms) puffs of 50 mM KCl. Cyclopiazonic acid (CPA; 5 microM), an inhibitor of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), significantly decreased the peak amplitude, and slowed the decay, of the KCl-evoked Ca2+ transients in TGNs. The mitochondrial protonophore, carbonyl cyanide 3-chloro-phenylhydrazone (CCCP; 5 microM) significantly increased the peak amplitude of KCl-evoked Ca2+ transients. These data demonstrate that Ca2+ stores do play a major role in Ca2+ homeostasis in TGN cell bodies. To determine the role of the sodium-calcium exchanger (NCX) in KCl-evoked Ca2+ transients in TGNs, we inhibited the exchanger with KB-R7943 (10 microM), or by replacing Na+ with Li+. NCX inhibition did not affect either the peak amplitude or the decay kinetics of the KCl-evoked Ca2+ transients. Therefore, the NCX does not play a significant role in removing cytosolic Ca2+ from TGNs. To test whether the plasma membrane calcium-ATPase (PMCA) contributes to Ca2+ extrusion, we inhibited its activity by a shift to alkaline pH (9.0). At pH 9.0, both the peak amplitude and decay time of the KCl-evoked Ca2+ transient were increased significantly. These data suggest that, in TGNs, the PMCA is the major mechanism for removing cytosolic Ca2+ following electrical activity.

Animals↗
PubMed2005

Roles for leptin receptor/STAT3-dependent and -independent signals in the regulation of glucose homeostasis.

Leptin activates the long form of the leptin receptor (LRb) to control feeding and neuroendocrine function and thus regulate adiposity. While adiposity influences insulin sensitivity, leptin also regulates glucose homeostasis independently of energy balance. Disruption of the LRb/STAT3 signal in s/s mice results in hyperphagia, neuroendocrine dysfunction, and obesity similar to LRb null db/db mice. Insulin resistance and glucose intolerance are improved in s/s compared to db/db animals, however, suggesting that LRb/STAT3-independent signals may contribute to the regulation of glucose homeostasis by leptin. Indeed, caloric restriction normalized glycemic control in s/s animals, but db/db mice of similar weight and adiposity remained hyperglycemic. These differences in glucose homeostasis were not attributable to differences in insulin production between s/s and db/db animals but rather to decreased insulin resistance in s/s mice. Thus, in addition to LRb/STAT3-mediated adiposity signals, non-LRb/STAT3 leptin signals mediate an important adiposity-independent role in promoting glycemic control.

Amino Acid Substitution↗
PubMed2006

Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells.

Suppressor of cytokine signaling-3 (Socs-3) negatively regulates the action of various cytokines, as well as the metabolic hormones leptin and insulin. Mice with haploinsufficiency of Socs-3, or those with neuronal deletion of Socs-3, are lean and more leptin and insulin sensitive. To examine the role of Socs-3 within specific neurons critical to energy balance, we created mice with selective deletion of Socs-3 within pro-opiomelanocortin (POMC)-expressing cells. These mice had enhanced leptin sensitivity, measured by weight loss and food intake after leptin infusion. On chow diet, glucose homeostasis was improved despite normal weight gain. On a high-fat diet, the rate of weight gain was reduced, due to increased energy expenditure rather than decreased food intake; glucose homeostasis and insulin sensitivity were substantially improved. These studies demonstrate that Socs-3 within POMC neurons regulates leptin sensitivity and glucose homeostasis, and plays a key role in linking high-fat diet to disordered metabolism.

Animals↗
PubMed2006

An analysis of the Petri net based model of the human body iron homeostasis process.

In the paper a Petri net based model of the human body iron homeostasis is presented and analyzed. The body iron homeostasis is an important but not fully understood complex process. The modeling of the process presented in the paper is expressed in the language of Petri net theory. An application of this theory to the description of biological processes allows for very precise analysis of the resulting models. Here, such an analysis of the body iron homeostasis model from a mathematical point of view is given.

Cluster Analysis↗
PubMed2005

Altered iron homeostasis involvement in arsenite-mediated cell transformation.

Chronic exposure to low doses of arsenite causes transformation of human osteogenic sarcoma (HOS) cells. Although oxidative stress is considered important in arsenite-induced cell transformation, the molecular and cellular mechanisms by which arsenite transforms human cells are still unknown. In the present study, we investigated whether altered iron homeostasis, known to affect cellular oxidative stress, can contribute to the arsenite-mediated cell transformation. Using arsenite-induced HOS cell transformation as a model, it was found that total iron levels are significantly higher in transformed HOS cells in comparison to parental control HOS cells. Under normal iron metabolism conditions, iron homeostasis is tightly controlled by inverse regulation of ferritin and transferrin receptor (TfR) through iron regulatory proteins (IRP). Increased iron levels in arsenite transformed cells should theoretically lead to higher ferritin and lower TfR in these cells than in controls. However, the results showed that both ferritin and TfR are decreased, apparently through two different mechanisms. A lower ferritin level in cytoplasm was due to the decreased mRNA in the arsenite-transformed HOS cells, while the decline in TfR was due to a lowered IRP-binding activity. By challenging cells with iron, it was further established that arsenite-transformed HOS cells are less responsive to iron treatment than control HOS cells, which allows accumulation of iron in the transformed cells, as exemplified by significantly lower ferritin induction. On the other hand, caffeic acid phenethyl ester (CAPE), an antioxidant previously shown to suppress As-mediated cell transformation, prevents As-mediated ferritin depletion. In conclusion, our results suggest that altered iron homeostasis contributes to arsenite-induced oxidative stress and, thus, may be involved in arsenite-mediated cell transformation.

Antioxidants↗
PubMed2016

The impact of metagenomic interplay on the mosquito redox homeostasis.

Mosquitoes are exposed to oxidative challenges throughout their life cycle. The primary challenge comes from a blood meal. The blood digestion turns the midgut into an oxidative environment, which imposes pressure not only on mosquito fecundity and other physiological traits but also on the microbiota in the midgut. During evolution, mosquitoes have developed numerous oxidative defense mechanisms to maintain redox homeostasis in the midgut. In addition to antioxidants, SOD, catalase, and glutathione system, sufficient supply of the reducing agent, NADPH, is vital for a successful defense against oxidative stress. Increasing evidence indicates that in response to oxidative stress, cells reconfigure metabolic pathways to increase the generation of NADPH through NADP-reducing networks including the pentose phosphate pathway and others. The microbial homeostasis is critical for the functional contributions to various host phenotypes. The symbiotic microbiota is regulated largely by the Duox-ROS pathway in Drosophila. In mosquitoes, Duox-ROS pathway, heme-mediated signaling, antimicrobial peptide production and C-type lectins work in concert to maintain the dynamic microbial community in the midgut. Microbial mechanisms against oxidative stress in this context are not well understood. Emerging evidence that microbial metabolites trigger host oxidative response warrants further study on the metagenomic interplay in an oxidative environment like mosquito gut ecosystem. Besides the classical Drosophila model, hematophagous insects like mosquitoes provide an alternative model system to study redox homeostasis in a symbiotic metagenomic context.

Animals↗
PubMed2004

Iron homeostasis and inherited iron overload disorders: an overview.

Iron is an ubiquitous metal of vital importance to the normal physiologic processes of many organisms. Recent discoveries of mutations in genes that lead to inherited iron overload diseases have advanced the understanding of iron homeostasis in humans. This article provides an overview of the human iron cycle, regulation of iron homeostasis, how perturbations in this homeostasis lead to iron overload disease in adults and children, and strategies for diagnosis of inherited iron overload.

Antimicrobial Cationic Peptides↗
PubMed2005

Mutations in the cueA gene encoding a copper homeostasis P-type ATPase reduce the pathogenicity of Pseudomonas aeruginosa in mice.

A sequencing project identified a putative copper homeostasis gene, cueA, in Pseudomonas aeruginosa strain PAO1. Strains with mutations of the cueA gene, encoding a P-type ATPase linked to copper homeostasis in P. putida, displayed greater sensitivity to copper compared to wild-type bacteria using MIC determinations and in vitro passage in growth media with different concentrations of copper added. An LD50 assay showed a cueA deletion mutant was 50-fold more attenuated than wild-type strain PAO1 bacteria. Complementation of the cueA mutation restored in vitro tolerance to copper and virulence in a systemic model of infection to near wild-type levels. Competition assays between cueA mutants and wild-type P. aeruginosa strains demonstrated 20-fold attenuation by the cueA mutants within spleens of mice. This data suggests the P. aeruginosa CueA protein may be important in maintaining copper homeostasis both in vitro and in vivo.

Adenosine Triphosphatases↗
PubMed2005

Intrinsic lymphotoxin-beta receptor requirement for homeostasis of lymphoid tissue dendritic cells.

The factors regulating dendritic cell (DC) development and homeostasis are incompletely understood. Here, we demonstrate that DCs express the lymphotoxin (LT)-beta receptor (LT beta R) and that in mice lacking the LT beta R in hematopoietic cells, spleen, and lymph node, CD8- DC numbers are reduced. B cells are a key source of LT alpha 1 beta 2 for splenic DC homeostasis, and transgenic overexpression of LT alpha 1 beta 2 on B cells leads to expansion of the CD8- DC compartment. Furthermore, we find that about 5% of splenic DCs are undergoing cell division, and the number of dividing CD8- DCs is disproportionately reduced in the absence of the LT beta R. In parabiosis experiments, splenic DCs were only partially replaced by circulating precursors over a 6 week period. We conclude that LT alpha 1 bet a2 acts on DCs or DC precursors to promote DC homeostasis, and we suggest that DC proliferation is an important pathway for locally maintaining these cells in the steady state.

Animals↗
PubMed2005

IL-7: maintaining T-cell memory and achieving homeostasis.

During an immune response, peripheral T-cell populations expand and then contract as the response subsides, thus maintaining a fairly constant number of CD4 and CD8 T cells throughout the life of the individual. The important factors that control this homeostasis are now beginning to be understood. Interleukin-7 (IL-7) has emerged as a central regulator of the survival and homeostasis of CD4 and CD8 T cells. Both naive and memory T-cell populations are highly dependent on the presence of IL-7 for their persistence and survival. In this Review, we discuss the role of IL-7 in the survival and homeostasis of naive and memory T cells and how that role is regulated by other factors.

CD4-Positive T-Lymphocytes↗
PubMed2026

Phosphorylation and ubiquitination coordinate homeostasis of a tomato transporter responsible for fruit sugar accumulation.

Sugar transport mediated by different transporters is essential for maintaining sugar homeostasis in plants. Here, we report that phosphorylation and ubiquitination coordinate the homeostasis of a tomato (Solanum lycopersicum) sugar transporter SlSWEET16, revealing a new aspect of plant sugar homeostasis. SlSWEET16 is localized to plasma membrane and functions as a mono- and disaccharide transporter. SlSWEET16 mediates cellular sugar efflux, and CRISPR/Cas9-mediated knockout of SlSWEET16 leads to increased fruit sugar accumulation. Strikingly, the C-terminus of SlSWEET16 is subjected to both phosphorylation and ubiquitination. Two protein kinases including SlSnRK2.3 and SlSnRK2.4 associate with the C-terminus of SlSWEET16, resulting into an increase in the stability of SlSWEET16. Meanwhile, the C-terminus of SlSWEET16 also interacts with an E3 ubiquitin ligase SlTT3.1L2, which decreases the stability of SlSWEET16. SlSnRK2.3 and SlSnRK2.4 inhibit fruit sugar accumulation, whereas SlTT3.1L2 promotes it. Mutations of phosphorylated or ubiquitinated residues in SlSWEET16's C-terminus further corroborate the contribution of phosphorylation and ubiquitination to the stability of SlSWEET16 and fruit sugar accumulation. Our results reveal a multiple-protein regulatory module that integrates different post-translational modifications to control transporter-mediated fruit sugar accumulation.

Solanum lycopersicum↗
PubMed2004

From aging to virulence: forging connections through the study of copper homeostasis in eukaryotic microorganisms.

Recent years have witnessed an explosion in the breadth of investigations on transition metal homeostasis and the subsequent depth of our understanding of metals in biology. Many genes and proteins that serve in the uptake, distribution, sensing and detoxification of one such transition metal, copper, have been identified. Through genetic and biochemical studies, the molecular details of copper uptake are being elucidated, and evidence suggests a largely conserved mechanism for copper acquisition and distribution from yeast to humans. Investigations of the mitochondrial copper pathway reveal the complexity surrounding copper delivery to cytochrome oxidase and highlight additional roles for some of the participants in copper homeostasis, such as a copper chaperone that influences the subcellular distribution of its target for copper incorporation. Furthermore, our understanding of the structure and function of copper transporters, chaperones and cupro-proteins, coupled with the emergence of additional model systems, is providing surprising examples of the integration of copper homeostasis with other physiological and pathophysiological processes and states, such as cancer, aging and virulence.

Aging↗
PubMed2004

Application of a customized pathway-focused microarray for gene expression profiling of cellular homeostasis upon exposure to nicotine in PC12 cells.

Maintenance of cellular homeostasis is integral to appropriate regulation of cellular signaling and cell growth and division. In this study, we report the development and quality assessment of a pathway-focused microarray comprising genes involved in cellular homeostasis. Since nicotine is known to have highly modulatory effects on the intracellular calcium homeostasis, we therefore tested the applicability of the homeostatic pathway-focused microarray on the gene expression in PC-12 cells treated with 1 mM nicotine for 48 h relative to the untreated control cells. We first provided a detailed description of the focused array with respect to its gene and pathway content and then assessed the array quality using a robust regression procedure that allows for the exclusion of unreliable measurements while decreasing the number of false positives. As a result, the mean correlation coefficient between duplicate measurements of the arrays used in this study (control vs. nicotine treatment, three samples each) has increased from 0.974+/-0.017 to 0.995+/-0.002. Furthermore, we found that nicotine affected various structural and signaling components of the AKT/PKB signaling pathway and protein synthesis and degradation processes in PC-12 cells. Since modulation of intracellular calcium concentrations ([Ca(2+)](i)) and phosphatidylinositol signaling are important in various biological processes such as neurotransmitter release and tissue pathogenesis including tumor formation, we expect that the homeostatic pathway-focused microarray potentially can be used for the identification of unique gene expression profiles in comparative studies of drugs of abuse and diverse environmental stimuli, such as starvation and oxidative stress.

Animals↗
PubMed2026

Human brown fat metabolism associates with systemic branched-chain amino acids homeostasis.

Circulating branched-chain amino acids (BCAAs) are linked with insulin resistance, but the human tissues contributing to systemic BCAA homeostasis remain incompletely defined. Brown adipose tissue (BAT) is a metabolically active adipose depot associated with favourable insulin sensitivity, yet its role in BCAA metabolism in humans remains unclear. We tested whether human BAT metabolism is associated with circulating BCAA levels, BAT-resident BCAA-catabolic signatures, and longitudinal changes in systemic BCAA homeostasis. We studied 83 adults who underwent metabolic phenotyping, PET-CT assessment of cold-stimulated BAT metabolism, and serum metabolomic profiling at room temperature and during acute mild cold exposure. Supraclavicular BAT biopsies from 25 participants were analysed by transcriptomics and metabolomics, and 40 participants were re-examined for circulating BCAA profiles after approximately five years. Participants with high BAT metabolism had lower circulating BCAA levels than those with low BAT metabolism. Within BAT, metabolically active individuals exhibited lower relative BCAA abundance together with higher expression of genes involved in BCAA catabolism. These BAT BCAA-catabolic signatures aligned with thermogenic capacity and indices of systemic insulin sensitivity. In contrast, individuals with low BAT metabolism showed increases in circulating BCAAs over five years. Integrative analyses further linked circulating lipopolysaccharide, a marker of metabolic endotoxemia, with higher BAT BCAA and aminomalonate abundance, together with transcriptional patterns involving inflammatory and mitochondrial pathways. Together, these findings identify human BAT metabolism as a tissue phenotype linked to systemic BCAA homeostasis and extend the role of human BAT beyond thermogenesis, suggesting that BAT-associated BCAA handling may contribute to systemic metabolic health.

Humans↗