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PubMed1993

Disordered water homeostasis and cognitive impairment in schizophrenia.

To investigate a possible association between disordered water homeostasis and cognitive impairment in schizophrenia, neuropsychological tests were applied to 16 schizophrenic patients with severely deranged water homeostasis and to 16 matched schizophrenic controls. The patients with disordered water homeostasis tended to obtain poorer scores than the controls throughout, the differences being statistically significant for two of the tests (Wechsler Memory Scale Visual Reproduction and Trial Marking Test part A). These results were not ascribable to differences in the duration of the illness, premorbid IQ, medication, or electroconvulsive therapy received, or prominence of any particular symptoms. The results suggest the co-existence of disordered water homeostasis and cognitive impairment in a subset of schizophrenic patients.

Adult↗
PubMed1985

Relationship between Na+-dependent cytoplasmic pH homeostasis and Na+-dependent flagellar rotation and amino acid transport in alkalophilic Bacillus.

The cytoplasmic pH homeostasis of alkalophilic Bacillus strains required the presence of Na+ in the medium, and Li+ was found to be equivalently substitutable for Na+. Flagellar rotation and amino acid transport of these bacteria also required Na+ but Li+ was not substitutable for Na+. Na+ concentration of about 1 mM was enough for the cytoplasmic pH homeostasis, while more than 10 mM Na+ was required for the full activities of flagellar rotation and amino acid transport. The addition of 150 mM ethanolamine to the cells at pH 9.6 disrupted the pH homeostasis and increased the cytoplasmic pH close to the external pH. Under this condition, however, flagellar rotation and amino acid transport were not so much affected. Thus, it is clear that flagellar rotation and amino acid transport themselves require the presence of Na+ in the medium, independent of the Na+-dependent cytoplasmic pH homeostasis.

Amino Acids↗
PubMed1994

Disturbances of the neuronal calcium homeostasis in the aging nervous system.

Maintenance of the cellular calcium homeostasis plays an important role for neuronal cell function and interneuronal cell to cell communication. Therefore, alterations of the neuronal Ca2+ homeostasis may play a crucial role for brain aging in general and for age-related deficits in cognitive functions particularly. Numerous studies indicate various disturbances of the Ca2+ homeostasis on different levels like Ca2+ channel properties, 45Ca2+ uptake, or Ca2+ binding proteins. Investigations on alterations of the free intracellular calcium concentration ([Ca2+]i) in presynaptic synaptosomal preparations led to inconsistent results reporting increased or unchanged [Ca2+]i in aged animals. Postsynaptic alterations of [Ca2+]i have been investigated mainly indirectly by electrophysiological methods and revealed prolonged Ca(2+)-dependent afterhyperpolarization or prolonged Ca2+ spike duration. By using acutely dissociated mouse brain cells it was possible for the first time to evaluate age-dependent alterations of postsynaptic [Ca2+]i directly. In neurons of aged mice basal [Ca2+]i was reduced and depolarization-induced rise in [Ca2+]i was also reduced, probably as a result of increased activation of Ca(2+)-dependent mechanisms terminating Ca(2+)-influx. Depolarization-induced, Ca(2+)-mediated inositolphosphate accumulation was also increased in aged animals. This leads to the conclusion that Ca(2+)-dependent intracellular processes become more sensitive during aging. Investigations about the effect of beta-amyloid on the Ca2+ homeostasis in the same system revealed a small but consistent destabilizating effect of this peptide on K(+)-induced rise in [Ca2+]i which may result in chronically increased neuronal vulnerability. Together with increased Ca2+ sensitivity during aging this might be one of the reasons for the increasing prevalence of Alzheimer's disease (AD) with aging.

Aging↗
PubMed2005

Identification of genes needed for regeneration, stem cell function, and tissue homeostasis by systematic gene perturbation in planaria.

Planarians have been a classic model system for the study of regeneration, tissue homeostasis, and stem cell biology for over a century, but they have not historically been accessible to extensive genetic manipulation. Here we utilize RNA-mediated genetic interference (RNAi) to introduce large-scale gene inhibition studies to the classic planarian system. 1065 genes were screened. Phenotypes associated with the RNAi of 240 genes identify many specific defects in the process of regeneration and define the major categories of defects planarians display following gene perturbations. We assessed the effects of inhibiting genes with RNAi on tissue homeostasis in intact animals and stem cell (neoblast) proliferation in amputated animals identifying candidate stem cell, regeneration, and homeostasis regulators. Our study demonstrates the great potential of RNAi for the systematic exploration of gene function in understudied organisms and establishes planarians as a powerful model for the molecular genetic study of stem cells, regeneration, and tissue homeostasis.

Animals↗
PubMed2006

Influence of an anti-diabetic foot ulcer formula and its component herbs on tissue and systemic glucose homeostasis.

Complications of diabetes impose major public health burdens worldwide. The positive effect of a Radix Astragali-based herbal preparation on healing diabetic foot ulcers in patients has been reported. Formula 1 is also referred as the 'Herbal drink to strengthen muscle and control swelling'. This formula contains six Chinese medical herbs, including Radix Astragali, Radix Rehmanniae, Rhizoma Smilacis Chinensis, Rhizoma Atractylodis Macrocephalae, Radix Polygoni Multiflori Preparata, and Radix Stephania Tetrandrae. Three of these herbs (Radix Astragali, Radix Rehmanniae, Rhizoma Atractylodis Macrocephalae) are commonly used in different anti-diabetic formulae of Chinese medicine. The objective of the current study is to use an interdisciplinary approach to test the hypothesis that Formula 1 and its components influence tissue and systemic glucose homeostasis. In vitro and in vivo models have been established including: (1) glucose absorption into intestinal brush border membrane vesicles (BBMV); (2) gluconeogenesis by H4IIE hepatoma cells; (3) glucose uptake by 3T3-L1 adipocytes and Hs68 skin fibroblasts; (4) normalization of glycaemic control in a diabetic rat model. The results of in vitro studies indicated that all herbal extracts can modify cellular glucose homeostasis. Since Formula 1 and Rhizoma Smilacis Chinensis extracts demonstrated potent effects on modifying glucose homeostasis in multiple tissues in vitro, they were further studied for their anti-diabetic activities in vivo using a streptozotocin (STZ)-induced diabetic rat model. The results showed that Formula 1 and Rhizoma Smilacis Chinensis extracts did not significantly improve oral glucose tolerance or basal glycaemia in diabetic rats. In conclusion, the anti-diabetic foot ulcer Formula 1 contains ingredients active in modifying tissue glucose homeostasis in vitro but these biological activities could not be associated with improved glycaemic control of diabetes in vivo.

3T3 Cells↗
PubMed2006

The dual origins of affect in nightmares: the roles of physiological homeostasis and memory.

Strong negative affect is a key and distressing ingredient of nightmares. Affect in nightmares arises either from the new generation of affective states due to physiological imbalances that occur during sleep or from the reactivation of affect-laden memories. The disruption of physiological balance produces a negative hedonic state, restoration of this balance produces a positive hedonic state, and when balance is attained, a neutral hedonic state results. As a result, hedonic states provoke behaviors in defense of homeostasis, then guide and terminate them. When, due to inadvertent behavior, a pronounced disruption of homeostasis occurs after sleep onset, the resultant strong negative hedonic state is likely to precipitate a nightmare and may lead to awakening. During normal wakefulness, associations of the interplay between stimuli and behaviors that disrupt homeostasis, those that restore homeostasis, and the affective states generated in the process, are committed to memory as affecto-cognitive ensembles. Sleep serves to build or rebuild neural architecture to effect development or to compensate for use- or disease-related wear (e.g. repair oxidative damage). Dreaming serves to synchronize or resynchronize such modified neural circuits with each other and those not modified. Hence, during dreaming, affecto-cognitive ensembles may get reactivated as part of the synchronization process. Where such an ensemble contains strong negative affect (i.e., due to strong affect generated during the original experience), a nightmare may be precipitated. Although both can occur throughout life, the latter type of nightmare is more likely in adults and the former in young children. For the latter memory-based behavioral therapy and for the former education and care are expected to be useful. For both types of nightmare, because strong negative affect is deemed dependent on noradrenergic outflow from the locus coeruleus, the administration of alpha-adrenergic antagonists will provide relief subject to certain caveats.

Affect↗
PubMed2006

Mechanisms underlying the rapid induction and sustained expression of synaptic homeostasis.

Homeostatic signaling systems are thought to interface with the mechanisms of neural plasticity to achieve stable yet flexible neural circuitry. However, the time course, molecular design, and implementation of homeostatic signaling remain poorly defined. Here we demonstrate that a homeostatic increase in presynaptic neurotransmitter release can be induced within minutes following postsynaptic glutamate receptor blockade. The rapid induction of synaptic homeostasis is independent of new protein synthesis and does not require evoked neurotransmission, indicating that a change in the efficacy of spontaneous quantal release events is sufficient to trigger the induction of synaptic homeostasis. Finally, both the rapid induction and the sustained expression of synaptic homeostasis are blocked by mutations that disrupt the pore-forming subunit of the presynaptic Ca(V)2.1 calcium channel encoded by cacophony. These data confirm the presynaptic expression of synaptic homeostasis and implicate presynaptic Ca(V)2.1 in a homeostatic retrograde signaling system.

Animals↗
PubMed2000

Alteration of mitochondrial calcium homeostasis by ammonia-induced activation of NMDA receptors in rat brain in vivo.

The aim of the present work was to assess the effects of activation of NMDA receptors in rat brain in vivo on calcium homeostasis in isolated non-synaptic brain mitochondria. We have shown recently that acute intoxication with large doses of ammonia leads to activation of NMDA receptors in rat brain in vivo. In the present work we injected rats with ammonium acetate to activate NMDA receptors in vivo and isolated non-synaptic mitochondria to assess calcium homeostasis. We also tested whether blocking NMDA receptors with MK-801 prevents effects on calcium homeostasis induced by ammonium injection. It is shown that activation of NMDA receptors in rat brain in vivo leads to a rapid increase in intramitochondrial calcium content followed by a reduction in the calcium capacity and calcium uptake rate in rat brain mitochondria. Activation of NMDA receptors resulted in increased spontaneous calcium efflux from rat brain mitochondria and in a strong inhibition of Na-induced and tert-butylhydroperoxide-induced calcium efflux. All these effects were prevented by previous blocking of NMDA receptors by injection of MK-801. Cyclosporin A did not affect any of the above parameters, indicating that the mitochondrial permeability transition pore does not play a role in calcium efflux under any of the conditions studied. The results reported indicate that ammonia-induced activation of NMDA receptors in rat brain in vivo alters mitochondrial calcium homeostasis at several different steps.

Ammonia↗
PubMed1999

Li+ protects nerve cells against destabilization of Ca2+ homeostasis and delayed death caused by removal of external Na+.

In experiments with fura-2 loaded cultured rat cerebellar granule cells we have compared the changes in [Ca2+]i homeostasis produced by replacement of external Na+ with the organic cation N-methyl-D-glucamine (NMDG) or Li+. The Na+/NMDG replacement caused an increase in baseline [Ca2+]i and a considerable delay in [Ca2+]i recovery following a glutamate (Glu) pulse in almost all the cells. In contrast Na+/Li+ replacement usually did not change baseline [Ca2+]i and produced only a small (if any) delay in the post-glutamate [Ca2+]i recovery. Previously [Storozhevykh et al. (1998) FEBS Lett. 431, 215-218] we revealed that perturbation of [Ca2+]i homeostasis caused by Na+/NMDG replacement cannot be explained by a reversal of the Na+/Ca2+ exchange but is mainly due to Ca2+ influx through NMDA channels activated by Na+ dependent release of endogenous excitatory amino acids ('reversed Glu uptake'). In the present work we confirmed this conclusion and obtained evidence suggesting that in contrast to NMDG Li+ interferes with the 'reversed Glu uptake' triggered by removal of external Na+. Thus it has been shown that the addition of Li+ (20 mM) to a Na+-free NMDG-containing solution suppressed both the perturbation of [Ca2+]i homeostasis and delayed neuronal death caused by Na+/NMDG replacement. Li+ is also able to abolish the [Ca2+]i response induced by PDC which at high concentrations (> 200 microM) is shown to stimulate the release of endogenous Glu. In contrast to Na+/Li+, Na+/NMDG replacement greatly enhances [Ca2+]i increase caused by PDC. Control experiments showed that Na+/Li+ replacement does not decrease the [Ca2+]i response to the Glu pulse. Therefore we concluded that a considerable quantitative difference between the effects of Na+/NMDG and Na+/Li+ replacements on both [Ca2+]i homeostasis and cell viability resulted mainly from the ability of Li+ to attenuate the release of endogenous Glu in response to the removal of external Na+.

Animals↗
PubMed2003

Nuclear receptors in cholesterol catabolism: molecular biology of the enterohepatic circulation of bile salts and its role in cholesterol homeostasis.

Recent advances in bile-salt research have revolutionized thought pertaining to the regulation of cholesterol homeostasis by highlighting the molecular control of reverse cholesterol transport and cholesterol catabolism to bile acids. The latter involves both feed-forward and feedback regulation of bile-acid synthesis within the territory of the enterohepatic circulation of bile salts. Cholesterol is vital to advanced life forms because it has become essential for membrane structure and function and is a precursor to the synthesis of steroid hormones, vitamins A and D, and bile acids. The liver plays a major part in cholesterol metabolism in that it is capable of de novo cholesterol synthesis and uptake from high-density lipoprotein reverse cholesterol transport, low-density lipoprotein, and chylomicron remnant receptors, so that 50% of total body cholesterol is available to be catabolized to bile acids. Cholesterol catabolism to bile acids allows the eukaryote cell to maintain cholesterol homeostasis because it cannot degrade cholesterol's cyclopentanoperhydrophenanthrene ring. Bile-salt catabolic end products of cholesterol must also be regulated to maintain normal bile-acid pool size, secretion, and elimination to avoid bile-salt hepatocyte toxicity. Nuclear hormone receptors, after sensing inappropriate oxysterol and bile-salt levels, are transcription factors that initiate the genetic transactivation to modulate reverse cholesterol transport, cholesterol catabolism, and bile-acid metabolism contiguous to and within the enterohepatic circulation of bile salts so as to regulate cholesterol and bile-salt homeostasis, respectively. This new knowledge should spawn pharmacologic discoveries that modulate nuclear receptors for the treatment of disorders of cholesterol homeostasis.

Bile Acids and Salts↗
PubMed2000

Gonadal steroids and energy homeostasis in the leptin era.

Gonadal steroids influence food intake and body weight. Although the specific mechanisms underlying these effects are not clear, a consideration of their effects in the context of current models of energy homeostasis may ultimately lead to the identification of these mechanisms. When compared with leptin, the prototypical humoral signal of energy balance, sex steroids share many common properties related to food intake and body weight. Specifically, gonadal steroids circulate in proportion to fat mass and current energy balance, and administration of these compounds influences food intake, energy expenditure, body weight, and body composition. Moreover, both estrogens and androgens modulate central nervous system effectors of energy homeostasis that are targets for the action of leptin, including pathways that contain neuropeptide Y, pro-opiomelanocortin, or melanin-concentrating hormone. Sex steroids and leptin also regulate one another's production. Although gonadal steroids, unlike leptin, are clearly not critical to the maintenance of normal energy homeostasis, they do appear to function as physiologic modulators of this process. Identifying the specific central mediators of their effects will contribute to our understanding of their role in energy homeostasis.

Body Weight↗
PubMed2006

An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis.

The sterol regulatory element binding protein (SREBP) family of transcription activators are critical regulators of cholesterol and fatty acid homeostasis. We previously demonstrated that human SREBPs bind the CREB-binding protein (CBP)/p300 acetyltransferase KIX domain and recruit activator-recruited co-factor (ARC)/Mediator co-activator complexes through unknown mechanisms. Here we show that SREBPs use the evolutionarily conserved ARC105 (also called MED15) subunit to activate target genes. Structural analysis of the SREBP-binding domain in ARC105 by NMR revealed a three-helix bundle with marked similarity to the CBP/p300 KIX domain. In contrast to SREBPs, the CREB and c-Myb activators do not bind the ARC105 KIX domain, although they interact with the CBP KIX domain, revealing a surprising specificity among structurally related activator-binding domains. The Caenorhabditis elegans SREBP homologue SBP-1 promotes fatty acid homeostasis by regulating the expression of lipogenic enzymes. We found that, like SBP-1, the C. elegans ARC105 homologue MDT-15 is required for fatty acid homeostasis, and show that both SBP-1 and MDT-15 control transcription of genes governing desaturation of stearic acid to oleic acid. Notably, dietary addition of oleic acid significantly rescued various defects of nematodes targeted with RNA interference against sbp-1 and mdt-15, including impaired intestinal fat storage, infertility, decreased size and slow locomotion, suggesting that regulation of oleic acid levels represents a physiologically critical function of SBP-1 and MDT-15. Taken together, our findings demonstrate that ARC105 is a key effector of SREBP-dependent gene regulation and control of lipid homeostasis in metazoans.

Amino Acid Sequence↗
PubMed2006

Genetic dissection of neuronal pathways controlling energy homeostasis.

Recent research has identified a number of genes playing critical roles in the central regulation of energy homeostasis. Subsequently, models of the neurocircuitry regulating energy balance have been suggested, although their physiological relevance remains mostly untested. Using the Cre/loxP system, we can now genetically dissect these neurocircuits and establish the specific roles of these genes in small neuronal subpopulations. Here we focus on two receptors shown to be critical in the central regulation of energy homeostasis: leptin (LepR) and melanocortin-4 receptors (MC4R). Mice and humans deficient in either leptin or melanocortin signaling are severely obese. A prominent model of leptin action places the arcuate nucleus of the hypothalamus, and in particular arcuate proopiomelanocortin (POMC) neurons, at the center stage of energy balance regulation. By deleting LepR specifically from POMC neurons in mice, we showed that LepR on POMC neurons are required but not solely responsible for leptin's regulation of body weight homeostasis. Thus, LepR on other neurons must also be critically important in leptin-mediated regulation of body weight homeostasis. Data from MC4R-deficient mice have shown that MC4Rs regulate both sides of the energy intake/energy expenditure balance. Our recent experiments used MC4R-deficient mice with restored MC4R expression only in the paraventricular hypothalamus and a subpopulation of amygdala neurons. We showed that MC4Rs in the paraventricular hypothalamus and/or amygdala are sufficient to control food intake but that MC4Rs elsewhere control energy expenditure, thereby discovering the novel concept of functional and anatomical divergence of MC4Rs.

Animals↗
PubMed2004

B chromosomes and developmental homeostasis in the yellow-necked mouse, Apodemus flavicollis (Rodentia, Mammalia): effects on nonmetric traits.

B chromosomes are found in almost all populations of the yellow-necked mouse, Apodemus flavicollis (Rodentia, Mammalia). Their effects on developmental homeostasis in this species were analyzed using morphological nonmetric traits (number of foramina) in a sample of 218 animals from locality Mt Jastrebac in the former Yugoslavia. Variations of the parameters of developmental homeostasis (the degree of fluctuating asymmetry--FA, the number of asymmetrical characters per individual--NA, and the total phenotypic variability--PV) were examined in three groups: in animals without Bs, with one B chromosome, and with more than one B chromosome. Significant differences in the level of FA between groups of animals were found for two characters. Carriers of one B chromosome displayed the highest level of phenotypic variability. Parameters of developmental stability (DS) were monitored in the population in which significant variations in the frequency of animals with Bs (fB) were established during the season earlier. The FA levels for four foramina out of a total of 12 examined followed the changes of frequencies of animals with Bs. Furthermore, a significant seasonal correlation between NA and fB was found. The presence of B does not cause a disturbance of homeostasis in a way that allows changes in homeostasis to be directly related to B chromosome's presence. However, carriers of B react differently to environmental changes than do noncarriers.

Animals↗
PubMed2003

Protein uptake disturbs collagen homeostasis in proximal tubule-derived cells.

BACKGROUND: Interstitial fibrosis is of major importance for the deterioration of renal function, leading to uremia. Interaction of filtered proteins with proximal tubular cells is important for the onset and development of tubulointerstitial damage. METHODS: We investigated the effects of protein endocytosis on collagen homeostasis and signaling pathways of proximal tubule-derived cells (OK cells, LLC-PK1 cells), which express the endocytic machinery typical for the proximal tubule (megalin and cubilin), and compared it to renal epithelial cells with low endocytic activity (MDCK, IHKE1, NHE3-deficient OK cells). Collagen homeostasis was assessed by proline incorporation, ELISA, and Western blot. Matrix metalloproteinase (MMP) activity was assessed by gelatinase assay. Signaling pathways were monitored by reporter gene assay. RESULTS: Albumin, glycated albumin, fatty acid-free albumin, or globulins led to an increase of secreted collagen (types I, III, and IV) in OK and LLC-PK1 cells. In cells with low protein uptake activity, albumin exposure inhibited collagen secretion. Western blot analysis showed an increase of cellular collagen. MMP activity was significantly decreased by albumin exposure. Furthermore, albumin exposure led to activation of the NF-kappa B-, AP1-, NFAT-, SRE-, and CRE-pathways. Inhibition of NF-kappa B, PKC, or PKA partially reversed the effects of albumin. In addition, inhibition of albumin endocytosis reduced collagen secretion and activation of the signaling pathways. Discussion. The data show that endocytic uptake of proteins disturbs collagen homeostasis in proximal tubular cells. This disturbed matrix homeostasis probably supports the progression of interstitial fibrosis, which is of importance for the development of renal insufficiency.

Albumins↗
PubMed1999

Occurrence of Na(+)-Ca2+ exchange in the ciliate Euplotes crassus and its role in Ca2+ homeostasis.

Ciliates possess diverse Ca2+ homeostasis systems, but little is known about the occurrence of a Na(+)-Ca2+ exchanger. We studied Na(+)-Ca2+ exchange in the ciliate Euplotes crassus by digital imaging. Cells were loaded with fura-2/AM or SBF1/AM for fluorescence measurements of cytosolic Ca2+ and Na+ respectively. Ouabain pre-treatment and Na+o substitution in fura-2/AM-loaded cells elicited a bepridil-sensitive [Ca2+]i rise followed by partial recovery, indicating the occurrence of Na(+)-Ca2+ exchanger working in reverse mode. In experiments on prolonged effects, ouabain, Na+o substitution, and bepridil all caused Ca2+o-dependent [Ca2+]i increase, showing a role for Na(+)-Ca2+ exchange in Ca2+ homeostasis. In addition, by comparing the effect of orthovanadate (affecting not only Ca2+ ATPase, but also Na(+)-K+ ATPase and, hence, Na(+)-Ca2+ exchange) to that of bepridil on [Ca2+]i, it was shown that Na(+)-Ca2+ exchange contributes to Ca2+ homeostasis. In electrophysiological experiments, no membrane potential variation was observed after bepridil treatment suggesting compensatory mechanisms for ion effects on cell membrane voltage, which also agrees with membrane potential stability after ouabain treatment. In conclusion, data indicate the presence of a Na(+)-Ca2+ exchanger in the plasma membrane of E. crassus, which is essential for Ca2+ homeostasis, but could also promote Ca2+ entry under specific conditions.

Animals↗
PubMed2002

Intracellular glucose 1-phosphate and glucose 6-phosphate levels modulate Ca2+ homeostasis in Saccharomyces cerevisiae.

The enzyme phosphoglucomutase plays a key role in cellular metabolism by virtue of its ability to interconvert Glc-1-P and Glc-6-P. It was recently shown that a yeast strain lacking the major isoform of phosphoglucomutase (pgm2Delta) accumulates a high level of Glc-1-P and exhibits several phenotypes related to altered Ca(2+) homeostasis when d-galactose is utilized as the carbon source (Fu, L., Miseta, A., Hunton, D., Marchase, R. B., and Bedwell, D. M. (2000) J. Biol. Chem. 275, 5431-5440). These phenotypes include increased Ca(2+) uptake and accumulation and sensitivity to high environmental Ca(2+) levels. In the present study, we overproduced the enzyme UDP-Glc pyrophosphorylase to test whether the overproduction of a downstream metabolite produced from Glc-1-P can also mediate changes in Ca(2+) homeostasis. We found that overproduction of UDP-Glc did not cause any alterations in Ca(2+) uptake or accumulation. We also examined whether Glc-6-P can influence cellular Ca(2+) homeostasis. A yeast strain lacking the beta-subunit of phosphofructokinase (pfk2Delta) accumulates a high level of Glc-6-P (Huang, D., Wilson, W. A., and Roach, P. J. (1997) J. Biol. Chem. 272, 22495-22501). We found that this increase in Glc-6-P led to a 1.5-2-fold increase in total cellular Ca(2+). We also found that the pgm2Delta/pfk2Delta strain, which accumulated high levels of both Glc-6-P and Glc-1-P, no longer exhibited the Ca(2+)-related phenotypes associated with high Glc-1-P levels in the pgm2Delta mutant. These results provide strong evidence that cellular Ca(2+) homeostasis is coupled to the relative levels of Glc-6-P and Glc-1-P in yeast.

Base Sequence↗
PubMed2006

Ghrelin: a hormone regulating food intake and energy homeostasis.

Regulation of energy homeostasis requires precise coordination between peripheral nutrient-sensing molecules and central regulatory networks. Ghrelin is a twenty-eight-amino acid orexigenic peptide acylated at the serine 3 position mainly with an n-octanoic acid, which is produced mainly in the stomach. It is the endogenous ligand of the growth hormone secretagogue (GHS) receptors. Since plasma ghrelin levels are strictly dependent on recent food intake, this hormone plays an essential role in appetite and meal initiation. In addition, ghrelin is involved in the regulation of energy homeostasis. The ghrelin gene is composed of four exons and three introns and renders a diversity of orexigenic peptides as well as des-acyl ghrelin and obestatin, which exhibit anorexigenic properties. Ghrelin stimulates the synthesis of neuropeptide Y (NPY) and agouti-related protein (AgRP) in the arcuate nucleus neurons of the hypothalamus and hindbrain, which in turn enhance food intake. Ghrelin-expressing neurons modulate the action of both orexigenic NPY/AgRP and anorexigenic pro-opiomelanocortin neurons. AMP-activated protein kinase is activated by ghrelin in the hypothalamus, which contributes to lower intracellular long-chain fatty acids, and this appears to be the molecular signal for the expression of NPY and AgRP. Recent data suggest that ghrelin has an important role in the regulation of leptin and insulin secretion and vice versa. The present paper updates the effects of ghrelin on the control of energy homeostasis and reviews the molecular mechanisms of ghrelin synthesis, as well as interaction with GHS receptors and signalling. Relationships with leptin and insulin in the regulation of energy homeostasis are addressed.

Animals↗