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At least 649 records · Page 36Linked to original sources

PubMed1997

Regional alterations in calcium homeostasis in the primate brain following chronic aluminium exposure.

The present study investigates the possible effects of chronic aluminium exposure on the various aspects of calcium homeostasis in the primate central nervous system. Aluminium administration caused a marked decline in the activity of Ca2+ ATPase in the monkey brain. The total calcium content was also significantly raised following aluminium exposure. Concomittant to the increase in the calcium content, the levels of lipid peroxidation were also augmented in the aluminium treated animals, thereby further accentuating the aluminium induced neuronal damage. In addition, aluminium had an inhibitory effect on the depolarization induced 45Ca2+ uptake via the voltage operated channels. The results presented herein, indicate that the toxic effects of aluminium could be mediated through modifications in the intracellular calcium homeostasis with resultant altered neuronal function.

Aluminum↗

PubMed1999

Dichlorvos induced alterations in glucose homeostasis: possible implications on the state of neuronal function in rats.

The present study was carried out to assess the effect of chronic dichlorvos exposure on various aspects of glucose homeostasis in different regions of rat brain. Dichlorvos administration caused a significant depletion in the brain glycogen content accompanied with an increase in the activity of glycogen phosphorylase. The activities of key glycolytic enzymes, hexokinase, phosphofructokinase and lactate dehydrogenase were decreased significantly following dichlorvos exposure. The decreased glycolytic flux was further reflected in terms of decreased regional glucose utilization, determined by measuring 14C-glucose influx. The altered neuronal glucose homeostasis had a significant impact on the neurobehavioural patterns of dichlorvos treated animals which was reflected in terms of severe deterioration in their memory and learning functions.

Acetylcholinesterase↗

PubMed1999

Effect of prolonged restriction of motor activity on primates hydration homeostasis.

It has been assumed that restriction of motor activity (hypokinesia) induces significant changes in body hydration homeostasis. Thus, the objective of this study was to measure body hydration level during prolonged hypokinesia (HK). The studies were done on 12 male Macaca Mulatta (rhesus monkeys) aged three to five years (4.75 to 6.96 kg) during a 15-day period of pre HK and a 90-day period of HK. All primates were divided equally into two groups: monkeys placed under vivarium conditions served as vivarium control primates (VCP) and monkeys subjected to HK served as hypokinetic primates (HKP). For simulation of the HK effect, the HKM group was kept for 90 days in small individual cages that restricted their movements in all directions without hindering food and water intakes. During the pre HK period of 15 days and the HK period of 90 days the following parameters were measured: total body water (TBW), extracellular fluid volume (EFV), intracellular fluid volume (IFV), circulating plasma volume (CPV) and interstitial fluid volume (IsFV), urinary and plasma sodium and potassium, fluid consumption and elimination in urine, and body weight. Significant (p < or = 0.01) decrease in the TBW, IFV, and CPV was observed in the HKP group when compared with the VCP group. In the HKP group EFV and IsFV decreased significantly (p < or = 0.01) when compared with the VCP group only in the initial seven days of the HK period, while after the 7th day progressive increase could be observed. Fluid loss, urinary electrolyte excretion and plasma electrolyte concentration increased significantly (p < or = 0.01), while fluid intakes decreased significantly (p < or = 0.01) in the HKP group when compared with the VCP group. In the HKP group body weight decreased significantly (p < or = 0.01) when compared with the VCP group. In the VCP group the measured parameters did not change significantly when compared with the baseline control values. It was concluded that prolonged exposure to HK induces significant changes in body hydration homeostasis while body dehydration in monkeys caused primarily due to decreased CPV.

Animals↗

PubMed2002

Calcium homeostasis and dichlorvos induced neurotoxicity in rat brain.

The present study was designed to investigate the possible effects of chronic dichlorvos exposure on the various aspects of calcium homeostasis in rat brain. Chronic dichlorvos administration caused significant rise in the intrasynaptosomal calcium levels. The activity of major calcium expelling enzyme i.e. Ca2+ATPase was found to be declined. Also, the depolarization induced calcium uptake via voltage operated calcium channels increased significantly. Concomitant to the increase in intrasynaptosomal calcium, calpain activity was found to be increased. The results presented herein, indicate that the toxic effects of dichlorvos could be mediated through modifications in the intracellular calcium homeostasis which may lead to impaired neuronal function.

Animals↗

PubMedDate not supplied

The leading role of mitochondrial depolarization in the mechanism of glutamate-induced disruptions in Ca2+ homeostasis.

Data obtained in studies of the nature of the correlation which we have previously observed [10,17] between mitochondrial depolarization and the level of disruption of Ca2+ homeostasis in cultivated brain neuronsare summarized. Experiments were performed on cultured cerebellar granule cells loaded with Fura-2-AM or rhodamine 123 to measure changes in cytoplasmic Ca2+ and mitochondrial potential during pathogenic treatments of the cells. Prolonged exposure to 100 microM glutamate induced a reversible increase in [Ca2+]i, which was accompanied by only a small degree of mitochondrial depolarization. A sharp increase in this mitochondrial depolarization, induced by addition of 3 mM NaCN or 300 microM dinitrophenol (DNP) to the glutamate-containing solution, resulted in further increase in [Ca2+]i, due to blockade of electrophoretic mitochondrial Ca2+ uptake. Prolonged exposure to CN- or DNP in the post-glutamate period maintained [Ca2+]i at a high level until the metabolic inhibitors were removed. In most cells, this plateau was characterized by low sensitivity to removal of external Ca2+, demonstrating that the mechanisms of Ca2+ release from neurons were disrupted. Addition of oligomycin, a blocker of mitochondrial ATP synthase/ATPase, to the solution containing glutamate and CN- or DNP eliminated the post-glutamate plateau. Parallel experiments with direct measurements of intracellular ATP levels ([ATP]) showed that profound mitochondrial depolarization induced by CN- or DNP sharply enhanced the drop in ATP due to glutamate, while oligomycin significantly weakened this effect of the metabolic inhibitors. Analysis of these data led to the conclusion that blockade of mitochondrial Ca2+ uptake and inhibition of ATP synthesis resulted from mitochondrial depolarization and plays a key role in the mechanism disrupting [Ca2+]i homeostasis after toxic exposure to glutamate.

Animals↗

PubMed2002

Altered Ca2+ homeostasis and impaired mitochondrial function in cardiomyopathy.

Altered Ca2+ homeostasis and myocyte death is a major characteristic of the hereditary cardiomyopathy in the dystrophic hamster. Despite numerous studies, the mechanisms that link calcium dysregulation and cell death in this animal model remain unclear. We have shown previously that the maintenance of mitochondrial Ca2+ homeostasis is essential for cell survival, and that loss of mitochondrial Ca2+ is closely correlated with cell death in cultured cells. Here, we have further investigated the role of mitochondrial Na+-Ca2+ exchange (NCE) in the development of cardiomyopathy in the dystrophic hamster. We found that the myocyte death was associated with elevated NCE activity together with a reduced level of matrix Ca2+, and impaired mitochondrial energetics. The upregulation of NCE activity in myopathic heart was also accompanied by enhanced expression of the sarcolemmal Na+-Ca2+ exchange (NCX) without alterations in the L-type Ca2+ channel expression. Treatment of dystrophic hamsters with diltiazem (a potent inhibitor of NCE and Ca2+ channels) prevented the occurrence of cell death and restored the normal expression of NCX. Our findings implicate the dysregulation of both sarcolemmal and mitochondrial Na+-Ca2+ exchange in cell death in the myopathic heart.

Animals↗

PubMed2003

Intestinal polyp formation in the Apcmin mouse: effects of levels of dietary calcium and altered vitamin D homeostasis.

This study evaluated the effects of various levels of dietary calcium on polyp formation, vitamin D homeostasis, and fecal bile acids in the Apcmin mouse. Female Apcmin mice were randomized to three groups and fed a purified diet with either half or double the level of calcium in control AIN-93G. Serum 25-OH-D and fecal bile acids were measured at weeks 0 and 12 of treatment. Mice were killed for polyp scoring by two observers blinded to treatment after 12 weeks. Results show there was no difference in polyp number or tumor load with dietary calcium in any treatment group. Serum 25-OH-D was reduced and total fecal bile acids were increased in animals that received the high calcium diet. We have previously shown that vitamin D supplementation diminishes polyp load; the lack of effect of an altered calcium diet seen here may be due to a disturbance in vitamin D homeostasis.

Animals↗

PubMed1998

Chromosomal localization of two human genes involved in phosphate homeostasis: the type IIb sodium-phosphate cotransporter and stanniocalcin-2.

Extracellular phosphate concentrations are maintained by coordinated regulation of specific homeostatic mechanisms. A novel gene, the type IIb sodium-phosphate cotransporter (Npt2b), was recently cloned and is expressed within intestinal tissues, indicating that the transporter may be an important regulator of phosphate reabsorption. Another gene, human stanniocalcin-2 (STC2), was previously shown to decrease phosphate uptake into kidney cells in vitro. Because of the important role that STC2 may play in phosphate homeostasis, we considered the peptide hormone a candidate for the phosphate wasting disease autosomal dominant hypophosphatemic rickets (ADHR), previously localized to chromosome 12p13. The purpose of our study was to determine the chromosomal localization of human NPT2b and STC2. In the present work, NPT2b was localized to human chromosome 4p15-p16, and STC2 to 5q33-tel. Because STC2 did not map to 12p13, the hormone was excluded as the ADHR gene, however it should be considered a candidate for other diseases involving phosphate homeostasis.

Calcium↗

PubMedDate not supplied

Airway dendritic cells: co-ordinators of immunological homeostasis and immunity in the respiratory tract.

The large quantities and complex mixtures of antigens encountered daily at airway mucosal and alveolar surfaces pose a major challenge to maintenance of immunological homeostasis in the respiratory tract. Amongst this myriad of antigens, the immune system must discriminate between innocuous components that can be tolerated by the host and potentially life-threatening pathogens that require a rapid immune response. Dendritic cells (DC) represent the principal cell type at these sites capable of processing antigens and delivering signals that initiate tolerogenic or immunogenic immune responses. This review will discuss the role of DC at the "front-line" of immune surveillance and homeostasis within the respiratory tract and their role in the pathogenesis of respiratory disease.

Allergens↗

PubMed2001

The role of Th2 cytokines in mast cell homeostasis.

Homeostatic mechanisms regulating mast cell numbers and function in peripheral tissues have largely focused on cytokines, such as stem cell factor, interleukin (IL)-3, IL-4, and IL-10, which regulate mast cell maintenance and proliferation. Despite these advances, little attention has been paid to the mechanisms that mediate mature mast cell turnover, and control of mast cell hyperplasia generated during Th2-mediated responses. These are important issues, as mast cells are now known to be multi-functional effector cells, that have the capacity to mediate both innate and Th2-induced immune responses. Numerous secretagogues may elicit mast cells to release a large number of important mediators that can cause chronic inflammation. Therefore, how mast cell homeostasis is regulated may have significant effects on normal physiology, and contribute to the genesis of inflammatory disease. Our laboratory has characterized an in vitro model of mast cell homeostasis, by which long-term exposure of murine bone-marrow-derived mast cells to the Th2-derived cytokines IL-3, IL-4, and IL-10, will induce downregulation of critical mast cell effector proteins such as Kit and Fcepsilon-RI, followed by mast cell apoptosis. These data offer a novel role for Th2 cytokines, acting to both initiate and resolve mast cell activation and proliferation. Loss of these signals may contribute to a multitude of diseases, such as mastocytosis and allergy

Animals↗

PubMed2003

Melanin has a role in Ca2+ homeostasis in human melanocytes.

We have examined whether melanin affects Ca2+ homeostasis in cultured normal human melanocytes. Intracellular Ca2+ concentrations ([Ca2+]i), were measured in four Caucasian and in three Negroid melanocyte cultures. Under resting conditions [Ca2+]i was around 100 nM in all cultures, but differences between cells within cultures were observed. All cultures responded to endothelin-1 (ET-1) with increases in [Ca2+]i and there were no differences between Caucasian and Negroid cultures. However, large differences in responses between cells within cultures were observed, indicating that melanocyte cultures are very heterogeneous. The addition of 2.5 mM CaCl2 to melanocytes kept in Ca2+-free medium resulted in rapid and transient increases in [Ca2+]i of up to 1500 nM. These increases were on average more than two times smaller in melanocyte cultures established from Negroid donors compared with Caucasian cultures. In addition, well melanized Caucasian melanocytes, cultured in the presence of 400 microM tyrosine and 10 mM NH4Cl, showed a reduced increase in cytoplasmic Ca2+ concentration upon the addition of extracellular Ca2+. The difference in maintaining Ca2+ homeostasis between poorly and well melanized melanocytes may be the result of the clearance of cytoplasmic Ca2+ into melanosomes and the greater capacity for this in the more pigmented melanocytes.

Ammonium Chloride↗

PubMed2002

Effects of epomediol on ethinyloestradiol-induced changes in glutathione homeostasis in the rat.

Epomediol is a synthetic terpenoid compound that has been reported to reduce ethinyloestradiol-induced cholestasis. The choleretic action of epomediol is related to an increase in both the bile acid-dependent and independent fractions of bile flow, but the role of glutathione metabolism and transport is still unknown. This study was aimed to evaluate if changes in glutathione homeostasis could contribute to the beneficial effects of epomediol in rats with ethinyloestradiol-induced cholestasis. When compared to control animals, ethinyloestradiol treatment resulted in a significant decrease in the liver concentration of reduced (GSH) and oxidized glutathione. Both GSH and oxidized glutathione concentrations returned to normal in animals receiving ethinyloestradiol plus epomediol. Ethinyloestradiol administration induced a significant decrease in plasma and renal GSH and the tripeptide was almost absent from bile. Combined treatment with epomediol plus ethinyloestradiol normalised renal GSH and both biliary and liver cysteine were significantly increased. Liver and kidney gamma-glutamyltranspeptidase activities were higher in rats receiving ethinyloestradiol and still remained elevated in animals with the combined treatment. Liver gamma-glutamylcysteine synthetase activity rose significantly by administration of ethinyloestradiol plus epomediol but the corresponding mRNA levels were not modified. Changes in glutathione homeostasis and higher biliary levels of GSH amino acid constituents could contribute to the beneficial effects of epomediol in rats with ethinyloestradiol-induced cholestasis.

Animals↗

PubMed2000

Iron homeostasis: insights from genetics and animal models.

Disorders that perturb iron balance are among the most prevalent human diseases, but until recently iron transport remained poorly understood. Over the past five years, genetic studies of patients with inherited iron homeostasis disorders and the analysis of mutant mice, rats and zebrafish have helped to identify several important iron-transport proteins. With information being mined from the genomes of four species, the study of iron metabolism has benefited enormously from positional-cloning efforts. Complementing the genomic strategy, targeted mutagenesis in mice has produced new models of human iron diseases. The animal models described in this review offer valuable tools for investigating iron homeostasis in vivo.

Animals↗

PubMed2002

RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-beta.

Osteoclasts are cells of monocyte/macrophage origin that erode bone matrix: regulation of their differentiation is central to the understanding of the pathogenesis and treatment of bone diseases such as osteoporosis. Signalling by RANKL (receptor activator of NF-kappaB ligand), also known as Tnfsf11, is essential for the induction of osteoclast differentiation, and it must be strictly regulated to maintain bone homeostasis. But it is not known whether RANKL signalling to the cell interior is linked to any regulatory mechanisms. Here we show that RANKL induces the interferon-beta (IFN-beta) gene in osteoclast precursor cells, and that IFN-beta inhibits the differentiation by interfering with the RANKL-induced expression of c-Fos, an essential transcription factor for the formation of osteoclasts. This IFN-beta gene induction mechanism is distinct from that induced by virus, and is dependent on c-Fos itself. Thus an autoregulatory mechanism operates-the RANKL-induced c-Fos induces its own inhibitor. The importance of this regulatory mechanism for bone homeostasis is emphasized by the observation that mice deficient in IFN-beta signalling exhibit severe osteopenia (loss of bone mass) accompanied by enhanced osteoclastogenesis. Our study places the IFN-beta system in a new context, and may offer a molecular basis for the treatment of bone diseases.

Animals↗

PubMed2000

Interleukin-7 mediates the homeostasis of naïve and memory CD8 T cells in vivo.

The naïve and memory T lymphocyte pools are maintained through poorly understood homeostatic mechanisms that may include signaling via cytokine receptors. We show that interleukin-7 (IL-7) plays multiple roles in regulating homeostasis of CD8+ T cells. We found that IL-7 was required for homeostatic expansion of naïve CD8+ and CD4+ T cells in lymphopenic hosts and for CD8+ T cell survival in normal hosts. In contrast, IL-7 was not necessary for growth of CD8+ T cells in response to a virus infection but was critical for generating T cell memory. Up-regulation of Bcl-2 in the absence of IL-7 signaling was impaired after activation in vivo. Homeostatic proliferation of memory cells was also partially dependent on IL-7. These results point to IL-7 as a pivotal cytokine in T cell homeostasis.

Adoptive Transfer↗

PubMed2001

ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis.

Glucose-responsive (GR) neurons in the hypothalamus are thought to be critical in glucose homeostasis, but it is not known how they function in this context. Kir6.2 is the pore-forming subunit of K(ATP) channels in many cell types, including pancreatic beta-cells and heart. Here we show the complete absence of both functional ATP-sensitive K+ (K(ATP)) channels and glucose responsiveness in the neurons of the ventromedial hypothalamus (VMH) in Kir6.2-/- mice. Although pancreatic alpha-cells were functional in Kir6.2-/-, the mice exhibited a severe defect in glucagon secretion in response to systemic hypoglycemia. In addition, they showed a complete loss of glucagon secretion, together with reduced food intake in response to neuroglycopenia. Thus, our results demonstrate that KATP channels are important in glucose sensing in VMH GR neurons, and are essential for the maintenance of glucose homeostasis.

ATP-Binding Cassette Transporters↗

PubMed1977

Relationship of renal ammonia production and potassium homeostasis.

Renal ammonia production appears to be intimately related to potassium homeostasis, and the two may comprise the components of a closed loop regulatory system. Studies with both intact organisms and in vitro systems indicate that potassium depletion stimulates and chronic potassium-loading suppresses renal ammonia production. An increase in ammoniagenesis has been shown to decrease potassium excretion. These observations suggest that changes in potassium modulate ammonia production, which in turn maintains hydrogen ion homeostasis and influences potassium excretion. Potassium depletion increases rat renal cortical ammonia production by altering metabolism in fashion identical to metabolic acidosis, but there is no convincing evidence that both processes are mediated by similar changes in either cellular hydrogen ion or potassium concentration. By contrast, potassium-loading, which depresses ammonia production, appears to affect primarily the outer medulla, a region that is not influenced by potassium depletion. Thus, potassium-loading apparently affects different portions of the renal tubule than depletion does, but the specific mechanism and physiologic significance of the different sites of action is unknown.

Ammonia↗

PubMed2004

Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis.

Costimulatory signals are required for activation of immune cells, but it is not known whether they contribute to other biological systems. The development and homeostasis of the skeletal system depend on the balance between bone formation and resorption. Receptor activator of NF-kappaB ligand (RANKL) regulates the differentiation of bone-resorbing cells, osteoclasts, in the presence of macrophage-colony stimulating factor (M-CSF). But it remains unclear how RANKL activates the calcium signals that lead to induction of nuclear factor of activated T cells c1, a key transcription factor for osteoclastogenesis. Here we show that mice lacking immunoreceptor tyrosine-based activation motif (ITAM)-harbouring adaptors, Fc receptor common gamma subunit (FcRgamma) and DNAX-activating protein (DAP)12, exhibit severe osteopetrosis owing to impaired osteoclast differentiation. In osteoclast precursor cells, FcRgamma and DAP12 associate with multiple immunoreceptors and activate calcium signalling through phospholipase Cgamma. Thus, ITAM-dependent costimulatory signals activated by multiple immunoreceptors are essential for the maintenance of bone homeostasis. These results reveal that RANKL and M-CSF are not sufficient to activate the signals required for osteoclastogenesis.

Adaptor Proteins, Signal Transducing↗