SEARCH · PubMed Health

Results for “HOMEOSTASIS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32Linked to original sources

PubMed2006

Glycogen autophagy in glucose homeostasis.

Glycogen autophagy, the sequestration and degradation of cell glycogen in the autophagic vacuoles, is a selective, hormonally controlled and highly regulated process, representing a mechanism of glucose homeostasis under conditions of demand for the production of this sugar. In the newborn animals, this process is induced by glucagon secreted during the postnatal hypoglycemia and inhibited by insulin and parenteral glucose, which abolishes glucagon secretion. Hormonal action is mediated by the cAMP/protein kinase A (induction) and phosphoinositides/mTOR (inhibition) pathways that converge on common targets, such as the protein phosphatase 2A to regulate autophgosomal glycogen-hydrolyzing acid glucosidase and glycogen autophagy. Intralysosomal phosphate exchange reactions, which are affected by changes in the calcium levels and acid mannose 6- and acid glucose 6-phosphatase activities, can modify the intralysosomal composition in phosphorylated and nonphosphorylated glucose and promote the exit of free glucose through the lysosomal membrane. Glycogen autophagy-derived nonphosphorylated glucose assists the hyaloplasmic glycogen degradation-derived glucose 6-phosphate to combat postnatal hypoglycemia and participates in other metabolic pathways to secure the fine tuning of glucose homeostasis during the neonatal period.

Animals↗

PubMed2005

Comparative sensitivity of rat cerebellar neurons to dysregulation of divalent cation homeostasis and cytotoxicity caused by methylmercury.

The objective of the present study was to determine the relative effectiveness of methylmercury (MeHg) to alter divalent cation homeostasis and cause cell death in MeHg-resistant cerebellar Purkinje and MeHg-sensitive granule neurons. Application of 0.5-5 microM MeHg to Purkinje and granule cells grown in culture caused a concentration- and time-dependent biphasic increase in fura-2 fluorescence. At 0.5 and 1 microM MeHg, the elevations of fura-2 fluorescence induced by MeHg were biphasic in both cell types, but significantly delayed in Purkinje as compared to granule cells. Application of the heavy-metal chelator, TPEN, to Purkinje cells caused a precipitous decline in a proportion of the fura-2 fluorescence signal, indicating that MeHg causes release of Ca(2+) and non-Ca(2+) divalent cations. Purkinje cells were also more resistant than granule cells to the neurotoxic effects of MeHg. At 24.5 h after-application of 5 microM MeHg, 97.7% of Purkinje cells were viable. At 3 microM MeHg there was no detectable loss of Purkinje cell viability. In contrast, only 40.6% of cerebellar granule cells were alive 24.5 h after application of 3 microM MeHg. In conclusion, Purkinje neurons in primary cultures appear to be more resistant to MeHg-induced dysregulation of divalent cation homeostasis and subsequent cell death when compared to cerebellar granule cells. There is a significant component of non-Ca(2+) divalent cation released by MeHg in Purkinje neurons.

Air Pollutants↗

PubMed2004

The niemann-pick disease genes; regulators of cellular cholesterol homeostasis.

Cellular cholesterol homeostasis is maintained through activation of the designated sterol regulatory element binding proteins and liver X receptor transcriptional pathways. Insight into the molecular mechanisms that regulate these pathways has come from the study of Niemann-Pick C (NPC) disease. Mutations in the NPC1 and NPC2 disease genes lead to lysosomal accumulation of cholesterol and defects in regulation of sterol homeostatic responses. NPC1 and NPC2 are key participants in intracellular cholesterol trafficking and are required for production of low-density lipoprotein cholesterol-derived oxysterols. In this review, the function of NPC1 and NPC2 in sterol trafficking and regulation of cholesterol homeostasis is examined. Study of the NPC proteins will further understanding of the mechanisms involved in atherogenesis.

Arteriosclerosis↗

PubMed2004

Alterations of FSH-stimulated progesterone production and calcium homeostasis in primarily cultured human luteinizing-granulosa cells induced by fenvalerate.

Fenvalerate, a synthetic pyrethroid, is widely used in agriculture and other domestic applications in China. Recently, Fenvalerate has been suspected to be one of the endocrine-disrupting chemicals (EDC). In this study, we investigated the effects of fenvalerate on follicle-stimulating hormone (FSH)-stimulated progesterone (P4) production by human ovarian luteinizing-granulosa cells (hGLCs). After 24 h incubation, fenvalerate inhibited FSH-stimulated P4 production. At the same time, FSH-stimulated cAMP also decreased. Due to calcium and Ca2+ -calmodulin (CaM) system involving gonadotropin-stimulated steroidogenesis by granulosa cells, we then evaluated the effects of fenvalerate on trifluoperazine (TFP)- and verapamil-driven FSH-stimulated P4 production. The results showed that calcium or calmodulin might play a role in fenvalerate-induced alterations in FSH-stimulated P4 biosynthesis. Then, the effects of fenvalerate on calcium homeostasis in hGLCs were studied. The result showed that 5 microM fenvalerate induced a slow increase in [Ca2+]i in hGLCs by using a fluorescent Ca2+ indicator fluo-3/AM. The changes in total concentration of CaM in hGLCs induced by fenvalerate were evaluated by a method of immunofluorescence. There is a significant increase in all treated groups. In summary, fenvalerate could inhibit FSH-stimulated P4 production. Also, fenvalerate interferes with calcium homeostasis in hGLCs. The effects of fenvalerate on FSH-stimulated ovarian steroidogenesis may be mediated partly through calcium signal.

Calcium↗

PubMed2006

Altered glucose homeostasis and oxidative impairment in pancreas of rats subjected to dimethoate intoxication.

The primary objective of this study was to investigate the effect of repeated sublethal doses of dimethoate (DM), an organophosphorus insecticide on glucose homeostasis, oxidative stress induction in pancreas and pancreatic damage in adult rats. Daily oral administration of DM (20 and 40 mg/kg b.w.) for 30 days induced a significant increase in blood glucose levels which was associated with impaired glucose tolerance. DM treatment resulted in elevated levels of pancreatic tissue specific markers such as activities of amylase and lipase in serum and pancreatic tissue indicating pancreatic dysfunction. Further, the activities of DT-diaphorase and NADPH-diaphorase in pancreas of DM treated rats were also found to be elevated. Interestingly, these biochemical dysfunctions were accompanied by a marked dose-related enhancement of lipid peroxidation and ROS levels in the pancreatic tissue indicating significant induction of oxidative damage. Additional evidence such as depletion in reduced glutathione levels and significant alterations in enzymic antioxidant defenses in pancreas among DM treated rats suggested induction of oxidative stress. Taken together, these findings provide experimental evidence that dimethoate at subchronic oral doses has the propensity to impair glucose homeostasis, induce significant pancreatic damage and also provide an account of the associated oxidative damage to pancreatic tissue in adult rats.

Administration, Oral↗

PubMed2004

Altered expression of genes related to zinc homeostasis in early mouse embryos exposed to di-2-ethylhexyl phthalate.

Numerous studies have shown that di-2-ethylhexyl phthalate (DEHP) is teratogenic in animals but the mechanism of developmental toxicity is not well understood. One hypothesis is altered zinc homeostasis. The present study has investigated the effect of DEHP exposure on several key genes in zinc metabolism (MT-I, MT-II, ZnT-1) for early mouse embryos exposed in utero. Time- and dose-dependent effects were examined using expression polymerase chain reaction (PCR) (relative to ACTB) and Western blot analysis of the maternal liver, embryonic brain, and visceral yolk sac at 9 days post-coitus (d.p.c.). Maternal exposure to 800 mg/kg DEHP increased the abundance of MT-I and MT-II transcripts in maternal liver at 3.0, 4.5 and 6.0 h after administration. MT-I and MT-II protein induction was confirmed by Western blot analysis. On the other hand, this exposure down-regulated both transcripts (MT-I, MT-II), as well as transcripts for a zinc transporter (ZnT-1), in the embryonic brain, but not the visceral yolk sac. To examine dose-response relationships, the experiment was repeated for DEHP exposures of 50, 200 and 800 mg/kg. The effect to MT-I and MT-II expression in the maternal liver became significant at the 200 mg/kg dose level. The contrasting effect to MT-I, MT-II and ZnT-1 expression in the embryo was also dose-dependent, and a benchmark computation for the dose resulting in a 5% change in the mean (BMD5) was estimated as 11.6 mg/kg for MT-I, 8.9 mg/kg for MT-II, and 6.6 mg/kg for ZnT-1. We conclude that DEHP exposure to pregnant dams at reasonably low levels during organogenesis stages can alter the expression of several key genes in embryonic zinc homeostasis.

Animals↗

PubMed2004

Lead nitrate-induced development of hypercholesterolemia in rats: sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis.

Changes in the gene expressions of hepatic enzymes responsible for cholesterol homeostasis were examined during the process of lead nitrate (LN)-induced development of hypercholesterolemia in male rats. Total cholesterol levels in the liver and serum were significantly increased at 3-72 h and 12-72 h, respectively, after LN-treatment (100 micromol/kg, i.v.). Despite the development of hypercholesterolemia, the genes for hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and other enzymes (FPPS, farnesyl diphosphate synthase; SQS, squalene synthase; CYP51, lanosterol 14alpha-demethylase) responsible for cholesterol biosynthesis were activated at 3-24 h and 12-18 h, respectively. On the other hand, the gene expression of cholesterol 7alpha-hydroxylase (CYP7A1), a catabolic enzyme of cholesterol, was remarkably suppressed at 3-72 h. The gene expression levels of cytokines interleukin-1beta (IL-1beta) and TNF-alpha, which activate the HMGR gene and suppress the CYP7A1 gene, were significantly increased at 1-3 h and 3-24 h, respectively. Furthermore, gene activation of SREBP-2, a gene activator of several cholesterogenic enzymes, occurred before the gene activations of FPPS, SQS and CYP51. This is the first report demonstrating sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis in LN-treated male rats. The mechanisms for the altered-gene expressions of hepatic enzymes in LN-treated rats are discussed.

Alkyl and Aryl Transferases↗

PubMed2003

Long-range, nonautonomous effects of activated Notch1 on tissue homeostasis in the nail.

Using an antibody directed against gamma-secretase-generated antigen unique to activated Notch1, we mapped Notch1 activation strictly to suprabasal cells in epidermis, nail matrix, and other skin appendages during normal development. The consequences of Notch1 activation in keratinizing nail cells were investigated in a transgenic mouse model. Ectopic activation of Notch1 in postmitotic cells within the nail keratogenous zone resulted in longer nails. BrdU labeling revealed an increased number of mitotic cells in transgenic nails. The matrix and keratogenous zone expanded distally due to the increase in cell numbers. The mitosis-promoting effects by a gene product expressed exclusively in postmitotic cells indicates a long-range effect of transgenic Notch1 on regulation of nail homeostasis. We demonstrate that activation of Notch1 in the keratogenous zone resulted in ectopic activation of Wnt signaling, the first such evidence in vertebrates. However, we detected little or no beta-catenin activation in proliferating matrix cells, indicating that Wnt is at most an indirect mediator of Notch-induced proliferation. These data support the existence of a novel, cell-nonautonomous role for Notch in maintaining homeostasis of stratified squamous epithelia by indirectly promoting mitosis in basally located cells.

Animals↗

PubMed2005

Positional cloning of the Ttc7 gene required for normal iron homeostasis and mutated in hea and fsn anemia mice.

Genes playing essential roles in iron homeostasis have yet to be identified. We report the discovery of a strong candidate gene affecting iron homeostasis in two allelic anemia mouse mutants: hea (hereditary erythroblastic anemia) and fsn (flaky skin). To clone this novel gene positionally, we established a large backcross, which generated a critical region of seven genes from which only one gene exhibited a mutation in hea mice. This was a deletion in Ttc7 (tetratricopeptide repeat domain 7) extending from exon 1 to exon 14. Correspondingly, the allelic variant fsn mice showed a mutation of an ETn retrotransposon integration into intron 14 of the Ttc7 gene, which results in an abnormal Ttc7 RNA transcript. TTC7 is a member of the TPR repeat protein family known to interact with other proteins, to facilitate transport, and to act as chaperone or scaffolding proteins. We speculate that TTC7 plays an important role in iron transport.

Amino Acid Sequence↗

PubMed2005

Transcriptional profiling of mefloquine-induced disruption of calcium homeostasis in neurons in vitro.

Mefloquine is associated with adverse neurological effects that are mediated via unknown mechanisms. Recent in vitro studies have shown that mefloquine disrupts neuronal calcium homeostasis via liberation of the endoplasmic reticulum (ER) store and induction of calcium influx across the plasma membrane. In the present study, global changes in gene expression induced in neurons in response to mefloquine-induced disruption of calcium homeostasis and appropriate control agents were investigated in vitro using Affymetrix arrays. The mefloquine transcriptome was found to be enriched for important regulatory sequences of the unfolded protein response and the drug was also found to induce key ER stress proteins, albeit in a manner dissimilar to, and at higher equivalent concentrations than, known ER-tropic agents like thapsigargin. Mefloquine also down-regulated several important functional categories of genes, including transcripts encoding G proteins and ion channels. These effects may be related to intrusion of extracellular calcium since they were also observed after glutamate, but not thapsigargin, hydrogen peroxide, or low-dose mefloquine treatment. Mefloquine could be successfully differentiated from other treatments on the basis of principle component analysis of its "calcium-relevant" transcriptome. These data may aid interpretation of expression of results from future in vivo studies.

Animals↗

PubMed2006

Deregulation of tissue homeostasis in endometria from patients with polycystic ovarian syndrome with and without endometrial hyperplasia.

OBJECTIVE: To study the proteins involved in endometrial homeostasis in PCOS women. METHODS: Protein expression of Ki67, Bcl-2, Bax, Pro-Caspase-3 and Caspase-3 by immunohistochemistry and/or Western blot, and DNA fragmentation using in situ 3'-end labeling of apoptotic cells, was measured in 9 samples of normal endometrium (NE), 12 PCOS endometria without treatment (PCOSE), 7 endometria from PCOS women with endometrial hyperplasia (HPCOSE) and 9 endometria from patients with endometrial hyperplasia (HE). RESULTS: Cell proliferation was higher in epithelium from PCOSE (P<0.05), HPCOSE and HE vs NE. A higher Bcl-2/Bax relative ratio in PCOSE and HPCOSE was observed, in absence of active Caspase-3 and scarce DNA fragmentation in the four groups of endometria studied. CONCLUSION: As the apoptosis was scarce in all of the groups studied, endometrial homeostasis deregulation in PCOS could be a result of increased proliferation. Therefore, the onset of endometrial hyperplasia in PCOS endometrium could be linked to inadequate cell proliferation, and concomitantly to inadequate cell survival.

Adult↗

PubMed2005

Effects of A1 adenosine receptor stimulation on the expression of genes involved in calcium homeostasis.

We investigated whether A(1) adenosine receptor stimulation affects expression of genes involved in calcium homeostasis, including sarcolemmal L-type Ca(2+) channel, Na(+)/Ca(2+) exchanger, sarcoplasmic reticulum (SR) Ca(2+)-ATPase, phospholamban, or ryanodine receptor. Three models of A(1) stimulation were used: i) an acute model, i.e. isolated perfused rat hearts treated for 120 min with 15 nM R-phenylisopropyladenosine (R-PIA), an A(1) receptor agonist; ii) a subacute model, i.e. rats treated with 1.5 mg/kg R-PIA e.v. and sacrificed after 24 h; iii) a transgenic model, i.e. mice overexpressing A(1) adenosine receptors. In all models gene expression was determined by RT-PCR, and oxalate-supported Ca(2+) uptake, representing SR Ca(2+) uptake, was measured in the crude homogenate. Significant increase in the expression of the phospholamban gene was observed in each model of A(1) stimulation, while the expression of the other four genes was not significantly modified. In the acute model, SR Ca(2+) uptake was unaffected, however in the subacute and transgenic models uptake rate was significantly reduced. In parallel experiments, hearts obtained from the subacute model demonstrated a significant reduction in irreversible tissue injury from 30 min of ischemia and 120 min of reperfusion. Increased resistance to ischemia has already been reported also in our transgenic model. In conclusion, A(1) adenosine receptor stimulation up-regulates phospholamban gene expression, which leads within 24 h to a reduced rate of SR Ca(2+) uptake. Changes in Ca(2+) homeostasis might contribute to the delayed cardioprotective effect of adenosine.

Adenosine↗

PubMed2003

Intra-myocyte ion homeostasis during ischemia-reperfusion injury: effects of pharmacologic preconditioning and controlled reperfusion.

BACKGROUND: This study determines whether controlled reperfusion or diazoxide improves intramyocyte Na(+) homeostasis using a porcine model of severe ischemia-reperfusion injury. METHODS: Three groups (n = 10 pigs per group) had 75 minutes of left anterior descending artery occlusion during bypass. Group 1 had no treatment (control group), group 2 had controlled reperfusion (500 mL warm cardioplegia) (controlled reperfusion group), and group 3 had diazoxide (50 micromol/L before left anterior descending artery occlusion) (diazoxide group). Biopsies were taken from the left anterior descending artery region before ischemia and at 3, 5, and 10 minutes postreperfusion. Intra-myocyte Na(+) and water contents were determined using atomic absorption spectroscopy, and Na(+) concentrations were calculated. RESULTS: Intra-myocyte Na(+) increased for the diazoxide group pigs at 3-minutes postreperfusion (21.9 +/- 2.9 vs 34.0 +/- 3.4 micromol/mL; p = 0.02), but decreased to 19.9 +/- 3.2 micromol/mL at 10 minutes postreperfusion (p = 1.0 vs baseline). At 10 minutes postreperfusion, intra-myocyte Na(+) in the controlled reperfusion group was lower than baseline (22.3 +/- 2.7 vs 17.2 +/- 3.1 micromol/mL; p < 0.001). Intra-myocyte Na(+) at 10 minutes postreperfusion for the diazoxide and controlled reperfusion groups was lower than for the control group (p < 0.05). CONCLUSIONS: Diazoxide and controlled reperfusion improved intra-myocyte Na(+) homeostasis after severe ischemia-reperfusion injury.

Animals↗

PubMed2003

The role of multidrug resistance proteins MRP1, MRP2 and MRP3 in cellular folate homeostasis.

Previously, we reported that the multidrug resistance proteins MRP1, MRP2 and MRP3 confer resistance to therapeutic antifolates by mediating their cellular extrusion. We now determined whether MRPs also play a role in controlling cellular homeostasis of natural folates. In MRP1, MRP2 and MRP3-transfected 2008 human ovarian carcinoma cells total cellular folate content was 32-38% lower than in 2008 cells (105+/-14pmolfolate/mgprotein) when grown in medium containing 2.3 microM folic acid (FA). Under these conditions cellular growth rates were not compromised. However, when cells were challenged under folate-depleted conditions with a short exposure (4 hr) to FA or leucovorin, MRP1 and MRP3 overexpressing cells were impaired in their growth. In contrast to wild-type cells, MRP1 transfected cells retained only 60% of the maximum growth when exposed to 500 nM leucovorin or 500 microM FA. For 2008/MRP1 and 2008/MRP3 cells FA growth stimulation capacity was dramatically decreased when, during a 4 hr exposure, metabolism into rapidly polyglutamatable and retainable dihydrofolate was blocked by the dihydrofolate reductase inhibitor trimetrexate. To retain growth under such conditions MRP1 overexpressing cells required much higher concentrations of FA (EC(50) > 500 microM) compared to 2008 cells (EC(50): 12 microM). These results suggest that down- and up-regulation of MRP1 (and MRP3) expression can influence cellular folate homeostasis, in particular when cellular retention by polyglutamylation of folates is attenuated.

Cell Division↗

PubMed1997

Modulation of cellular reducing equivalent homeostasis by alpha-lipoic acid. Mechanisms and implications for diabetes and ischemic injury.

The therapeutic potential of alpha-lipoic acid (thioctic acid) was evaluated with respect to its influence on cellular reducing equivalent homeostasis. The requirement of NADH and NADPH as cofactors in the cellular reduction of alpha-lipoic acid to dihydrolipoate has been reported in various cells and tissues. However, there is no direct evidence describing the influence of such reduction of alpha-lipoate on the levels of cellular reducing equivalents and homeostasis of the NAD(P)H/NAD(P) ratio. Treatment of the human Wurzburg T-cell line with 0.5 mM alpha-lipoate for 24 hr resulted in a 30% decrease in cellular NADH levels. alpha-Lipoate treatment also decreased cellular NADPH, but this effect was relatively less and slower compared with that of NADH. A concentration-dependent increase in glucose uptake was observed in Wurzburg cells treated with alpha-lipoate. Parallel decreases (30%) in cellular NADH/NAD+ and in lactate/pyruvate ratios were observed in alpha-lipoate-treated cells. Such a decrease in the NADH/NAD+ ratio following treatment with alpha-lipoate may have direct implications in diabetes, ischemia-reperfusion injury, and other pathologies where reductive (high NADH/NAD+ ratio) and oxidant (excess reactive oxygen species) imbalances are considered as major factors contributing to metabolic disorders. Under conditions of reductive stress, alpha-lipoate decreases high NADH levels in the cell by utilizing it as a co-factor for its own reduction process, whereas in oxidative stress both alpha-lipoate and its reduced form, dihydrolipoate, may protect by direct scavenging of free radicals and recycling other antioxidants from their oxidized forms.

Cells, Cultured↗

PubMed1999

Tissue-specific regulation of glutathione homeostasis and the activator protein-1 (AP-1) response in the rat conceptus.

Oxidative stress in the conceptus is characterized by an increased oxidized to reduced glutathione (GSSG:GSH) ratio and the induction of fos and jun mRNAs, transcripts for components of the activator protein-1 (AP-1) transcription factor. We investigated the role of glutathione homeostasis in the rat conceptus in the regulation of: (1) AP-1 expression and activity, and (2) the activities of glutathione-dependent cytoprotective enzymes. Glutathione content was enhanced with the addition of l-2-oxothiazolidine-4-carboxylate (OTC), a precursor of cysteine, a rate-limiting substrate in glutathione biosynthesis. Day 10 rat conceptuses were cultured for 44 hr with 0, 5, 10, or 20 mM OTC. High concentrations (10 and 20 mM) of OTC were embryotoxic. Incubation of the conceptus in 5 mM OTC caused mild (not statistically significant) embryotoxicity, increased significantly the embryonic glutathione content, prevented culture-induced oxidative stress, and inhibited the induction of AP-1 transcripts and DNA binding activity in the embryo. In contrast, in the yolk sac, 5 mM OTC failed to increase glutathione content or to prevent oxidative stress or AP-1 induction. Thus, regulation of glutathione status in the conceptus is tissue-specific. Glutathione S-transferase and glutathione peroxidase activities were increased approximately 50% in cultured embryos and yolk sacs. OTC treatment (5 mM) prevented this induction in the embryo, but not in the yolk sac, suggesting a role for glutathione homeostasis in the regulation of these enzymes. Tissue-specific regulation of glutathione status and of cytoprotective enzymes in the conceptus during organogenesis may impact on the consequences of insult with oxidative stress.

Animals↗

PubMed2000

Associated disturbances in calcium homeostasis and G protein-mediated cAMP signaling in bipolar I disorder.

BACKGROUND: Evidence of extensive cross-talk between calcium (Ca(2+))- and cAMP-mediated signaling systems suggests that previously reported abnormalities in Ca(2+) homeostasis in bipolar I (BP-I) patients may be linked to disturbances in the function of G proteins that mediate cAMP signaling. METHODS: To test this hypothesis, the beta-adrenergic agonist, isoproterenol, and the G protein activator, sodium fluoride (NaF), were used to stimulate cAMP production in B lymphoblasts from healthy and BP-I subjects phenotyped on basal intracellular calcium concentration ([Ca(2+)](B)). cAMP was measured by radioimmunoassay and [Ca(2+)](B) by ratiometric fluorometry with fura-2. RESULTS: Isoproterenol- (10 microM) stimulated cAMP formation was lower in intact B lymphoblasts from BP-I patients with high [Ca(2+)](B) (>/= 2 SD above the mean concentration of healthy subjects) compared with patients having normal B lymphoblast [Ca(2+)](B) and with healthy subjects. Although basal and NaF-stimulated cAMP production was greater in B lymphoblast membranes from male BP-I patients with high versus normal [Ca(2+)](B), there were no differences in the percent stimulation. This suggests the differences in NaF response resulted from higher basal adenylyl cyclase activity. CONCLUSIONS: These findings suggest that trait-dependent disturbances in processes regulating beta-adrenergic receptor sensitivity and G protein-mediated cAMP signaling occur in conjunction with altered Ca(2+) homeostasis in those BP-I patients with high B lymphoblast [Ca(2+)](B).

Adult↗

PubMed1999

Blood-brain barrier mechanisms involved in brain calcium and potassium homeostasis.

This study examined the potential roles of the plasma membrane Ca2+-ATPase (PMCA) at the blood-CSF and blood-brain barriers in brain Ca2+ homeostasis and blood-brain barrier Na+/K+-ATPase subunits in brain K+ homeostasis. During dietary-induced hypo- and hypercalcemia (0.59+/-0.06 and 1.58+/-0.12 mM [Ca2+]) there was no significant change in choroid plexus PMCA (Western Blots) compared to normocalcemic rats (plasma [Ca2+]: 1.06+/-0.11 mM). In contrast, PMCA in cerebral microvessels isolated from hypocalcemic rats was 150% greater than that in controls (p<0.001). Comparison of the alpha3 subunit of Na+/K+-ATPase from cerebral microvessels isolated from hypo-, normo- and hyperkalemic rats (2.3+/-0.1, 3.9+/-0.1 and 7. 2+/-0.6 mM [K+]) showed a 75% reduction in the amount of this isoform during hyperkalemia. None of the other Na+/K+-ATPase isoforms varied with plasma [K+]. These results suggest that both PMCA and the alpha3 subunit of Na+/K+-ATPase at the blood-brain barrier play a role in maintaining a constant brain microenvironment during fluctuations in plasma composition.

Animals↗