Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in norepinephrine synthesis, was determined in the mediobasal hypothalamus of adult male rats during acute and semistarvation. 3,4-Dihydroxyphenylalanine (DOPA) formed by TH was measured using high-performance liquid chromatography (HPLC). Acute starvation, as well as 3 weeks of semistarvation on a high-protein low-carbohydrate diet (CST PR) reduced TH activity significantly. Three weeks of a low-protein high-carbohydrate diet (CST KH) did not affect TH activity. While maximal velocity (Vmax) is significantly diminished in acute starvation and in semistarvation with a high-protein low-carbohydrate diet, Kd-values for tyrosine were not changed. These results suggest that TH activity in the brain contributes to decreased norepinephrine (NE) turnover in starvation.
 ...
PMID:Effect of starvation on hypothalamic tyrosine hydroxylase activity in adult male rats. 288 75

The effect of aging was evaluated on norepinephrine content of the heart (ventricles) and spleen of 3- and 24-month-old F344 and Sprague-Dawley rats utilizing a sensitive radioenzymatic assay. To assess sympathetic nervous system activity, the decline in organ norepinephrine content was compared in young and old F344 rats 6 hours after blockade of norepinephrine synthesis with alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor. Three conditions were studied: (a) normal, (b) brief starvation (54 hours), and (c) cold exposure (6 hours, 4 degrees C). There was no significant age-related difference in steady state organ norepinephrine concentration. Based on the response to alpha-methyl-p-tyrosine, aging did not affect the rate of heart and spleen norepinephrine synthesis and, therefore, sympathetic nervous system impulse activity during normal or cold stress conditions. Starvation, however, did not suppress sympathetic nervous system activity to the heart in old animals, as it did in the young rats.
 ...
PMID:Influence of aging and tyrosine hydroxylase inhibition on tissue levels of norepinephrine during stress. 612 30

Murine neuroblastoma cells have been widely used as a model system for neuronal cells as they can be induced to differentiate in culture by various stimuli, such as dibutyryl cyclic AMP (dbcAMP), prostaglandin, and serum starvation. The cells respond with assembly of microtubules, leading to neurite outgrowth, with increased activity of neuronal-specific enzymes, tyrosine hydroxylase, choline acetyltransferase and acetylcholine-esterase, and synthesis of neurotransmitters. The differentiated cells lose tumorigenicity. Cell-to-substratum adhesion is evidently crucial for neurone extension in vitro. Neurite outgrowth is induced by treatments that increase cell-to-substratum adhesion in some neuronal cell cultures. We have now identified the major high molecular weight proteins synthesized and secreted by murine C1300 neuroblastoma cells as fibronectin, laminin and type IV procollagen, of which the latter two were also found to be deposited in pericellular matrix form.
 ...
PMID:Basal lamina glycoproteins are produced by neuroblastoma cells. 743 74

Previous in vitro studies have shown that the presence of high levels of Bax protein accelerated the rate of cell death following growth factor deprivation and that the ratio of cell death repressor Bcl-2 to cell death effector Bax may determine the susceptibility to apoptosis. Both Bcl-2 and Bax protein expression has been detected in sympathetic neurons in vivo, and overexpression of bcl-2 in cultured sympathetic neurons prevented apoptosis after deprivation of nerve growth factor (NGF). In the present study, we investigated the expression of bax and bcl-2 in primary cultures of sympathetic neurons from rat superior cervical ganglia. Furthermore, we tested the effects of a partially phosphorothioated bax antisense oligodeoxynucleotide (ODN) on the survival of sympathetic neurons in cultures supplied with suboptimal concentrations of NGF (0.5 ng/ml). A constitutive expression of bax mRNA at high levels was detected by reverse transcription and polymerase chain reaction which did not change significantly following NGF reduction or treatment with bax antisense ODN. A decrease in Bcl-2 immunoreactivity was observed by immunocytochemistry in tyrosine hydroxylase-positive neurons when cultured under suboptimal NGF concentrations, whereas Bcl-2 immunolabeled non-neuronal cells were not affected. Maximal number of neurons was obtained in control cultures containing 50 ng/ml of NGF. Few neurons survived in cultures grown in 0.5 ng/ml of NGF for 2 days (12.0 +/- 1.5% of controls, mean +/- SEM). Addition of two control ODNs at 1 microM had no effect on neuronal survival (10.1 +/- 1.2% and 11.0 +/- 1.3%, respectively), while the number of neurons was significantly increased in NGF-reduced cultures treated with a bax antisense ODNs (1 microM) (31.5 +/- 1.9%). Administration of fluorescein-labeled ODNs demonstrated intracellular uptake into cultured neurons. Treatment with bax antisense ODNs caused a significant reduction of Bax protein levels in SCG neurons by 46 +/- 2.6% as assessed by immuno-cytochemistry and digital image analysis. Taken together, our data demonstrate a constitutive expression of bax mRNA in sympathetic neurons suggesting that activation of bax expression may not be required for neuronal cell death after NGF withdrawal. After changing to suboptimal NGF concentrations, the cell-specific reduction in Bcl-2 immunoreactivity preceded morphological signs of degeneration indicating that growth factor starvation may down-regulate neuronal bcl-2 expression. Treatment with bax antisense ODNs indicated that suppression of Bax protein synthesis may promote neuronal survival in the threshold situation of insufficient trophic support.
 ...
PMID:Antisense oligodeoxynucleotides to bax mRNA promote survival of rat sympathetic neurons in culture. 898 2

The Anorexia (anx) mutation causes reduced food intake in preweanling mice, resulting in death from starvation within 3-4 weeks. We have found serotonin (5HT) hyperinnervation in the anx brain; altered noradrenergic (NE) innervation may also mediate eating disorders. We examined the expression of synthetic or catabolic monoamine enzyme genes in brainstem nuclei: serotonin transporter (5HTT) and monoamine oxidase A (MAOA) in the raphe nuclei (RN), and MAOA, norepinephrine transporter (NET), and tyrosine hydroxylase (TH) in the locus ceruleus (LC). We compared 3-week old anx with control and 24-h food-deprived wildtype littermates using in situ hybridization to measure mRNA levels by quantitative autoradiography. The anx mutation was correlated with decreased MAOA mRNA in the LC (but not RN), decreased 5HTT mRNA in the RN, and a trend towards lower NET mRNA in the LC. Food deprivation decreased MAOA mRNA in the LC (but not RN), increased TH mRNA in the LC, and did not alter NET or 5HTT mRNA levels. Thus, the effect of the anx mutation on MAOA expression in the LC paralleled the effect of food-deprivation, but the anx mutation and food-deprivation had differential effects on the expression of TH, NET, and 5HTT genes. Decreased 5HTT expression in the anx RN is consistent with upregulation of serotonergic neurotransmission that may accompany 5HT hyperinnervation. Central NE levels or innervation may be altered in anx mice by decreased expression of NET and MAOA and a lack of TH upregulation induced by food deprivation as in wild-type mice.
 ...
PMID:Differential expression of monoamine oxidase A, serotonin transporter, tyrosine hydroxylase and norepinephrine transporter mRNA by anorexia mutation and food deprivation. 959 16

Dopamine-deficient (DD) mice cannot synthesize dopamine (DA) in dopaminergic neurons due to selective inactivation of the tyrosine hydroxylase gene in those neurons. These mice become hypoactive and hypophagic and die of starvation by 4 weeks of age. We used gene therapy to ascertain where DA replacement in the brain restores feeding and other behaviors in DD mice. Restoration of DA production within the caudate putamen restores feeding on regular chow and nest-building behavior, whereas restoration of DA production in the nucleus accumbens restores exploratory behavior. Replacement of DA to either region restores preference for sucrose or a palatable diet without fully rescuing coordination or initiation of movement. These data suggest that a fundamental difference exists between feeding for sustenance and the ability to prefer rewarding substances.
 ...
PMID:Dopamine production in the caudate putamen restores feeding in dopamine-deficient mice. 1143 Aug 14

(6R)-L-erythro-5,6,7,8-Tetrahydrobiopterin (BH4) is an essential cofactor for tyrosine hydroxylase (TH), tryptophan hydroxylase, phenylalanine hydroxylase, and nitric-oxide synthase. These enzymes synthesize neurotransmitters, e.g. catecholamines, serotonin, and nitric oxide (NO). We established mice unable to synthesize BH4 by disruption of the 6-pyruvoyltetrahydropterin synthase gene, the encoded protein of which catalyzes the second step of BH4 biosynthesis. Homozygous mice were born at the almost expected Mendelian ratio, but died within 48 h after birth. In the brain of homozygous mutant neonates, levels of biopterin, catecholamines, and serotonin were extremely low. The number of TH molecules was highly dependent on the intracellular concentration of BH4 at nerve terminals. Alteration of the TH protein level by modulation of the BH4 content is a novel regulatory mechanism. Our data showing that catecholaminergic, serotonergic, and NO systems were differently affected by BH4 starvation suggest the possible involvement of BH4 synthesis in the etiology of monoamine-based neurological and neuropsychiatric disorders.
 ...
PMID:Catecholamines and serotonin are differently regulated by tetrahydrobiopterin. A study from 6-pyruvoyltetrahydropterin synthase knockout mice. 1151 15

We have studied the effects of diet restriction (DR) to 60% and 40% of daily requirements, and tyrosine administration on cognitive function in mice, to define the nutritional-neurochemical interactions on autonomic tone involved in behavior and energy regulation. Cognitive function in the Morris Water maze was significantly impaired after 40% DR compared to both control and 60% DR. It was restored after tyrosine in association with increased M1 cholinergic and beta-adrenergic receptor function, and decreased alpha-adrenergic function. DR to 40% significantly decreased choline uptake (p <.05) and M1 receptor number (Bmax) (p <.05), without changes in affinity (Kd), choline acetyl transferase (ChAT) or acetyl cholinesterase (AChE) activity. Tyrosine administration significantly increased choline uptake (Bmax) (p <.05) and M1 density in the 40% DR (p <.01) without changes in affinity. ChAT activity was decreased after tyrosine--significantly after 40% DR (p <.05) while AChE was not affected. Both M1 mRNA and protein were not influenced by DR or tyrosine administration. Tyrosine hydroxylase mRNA was decreased significantly by 40% DR (p <.01). The effect of DR and tyrosine appeared to be both pre- and post-synaptic, indicating modulation of cholinergic activity by adrenergic tone. Nutritional effect on behavior and autonomic tone may have implications for the treatment of mood changes associated with weight loss and semi-starvation.
 ...
PMID:Diet restriction in mice causes a decrease in hippocampal choline uptake and muscarinic receptors that is restored by administration of tyrosine: interaction between cholinergic and adrenergic receptors influencing cognitive function. 1184 83

Dopamine-deficient (DD) mice have selective inactivation of the tyrosine hydroxylase gene in dopaminergic neurons, and they die of starvation and dehydration at 3-4 weeks of age. Daily injections of L-DOPA (50 mg/kg, i.p.) starting approximately 2 weeks after birth allow these animals to eat and drink enough for survival and growth. They are hyperactive for 6-9 h after receiving L-DOPA and become hypoactive thereafter. Because these animals can be tested in the presence or absence of DA, they were used to determine whether DA is necessary for learning to occur. DD mice were tested for learning to swim to an escape platform in a straight alley in the presence (30 min after an L-DOPA injection) or absence (22-24 h after an L-DOPA injection) of dopamine. The groups were split 24 h later and retested 30 min or 22-24 h after their last L-DOPA injection. In the initial test, DD mice without dopamine showed no evidence of learning, whereas those with dopamine had a learning curve similar in slope to controls but significantly slower. A retest after 24 h showed that DD mice can learn and remember in the absence of dopamine, leading to the inference that the lack of dopamine results in a performance/motivational decrement that masks their learning competence for this relatively simple task.
 ...
PMID:The role of dopamine in learning, memory, and performance of a water escape task. 1468 49

Behaviors modulated by dopamine appear to be conserved across species. In the model system Drosophila melanogaster, as in mammals, dopamine modulates female sexual receptivity, a simple form of learning and responses to drugs of abuse. Synthesis, reuptake and binding of dopamine are also evolutionarily conserved. Since stress has been shown to affect dopaminergic signaling pathways in mammals, we investigated the consequences of exposure to diverse stressors on dopaminergic physiology in the fruit fly, D. melanogaster. Animals were exposed to a metabolic stress (starvation), an oxidative stress (via the superoxide anion generator paraquat) or a mechanical stress (gentle vortexing). Sexual maturity, reproductive status, gender and type of stress differentially affected survival. The stress paradigms also resulted in alterations in the activity of tyrosine hydroxylase, the rate-limiting enzyme in dopamine biosynthesis. Exposure to these stressors perturbed female sexual receptivity and ovarian development, which are modulated by dopamine, suggesting that dopaminergic physiology is affected as a consequence of stress. Transgenic Drosophila with reduced levels of neuronal dopamine displayed an altered response to these stressors, suggesting that, as in mammals, dopamine is a key element in the stress response.
 ...
PMID:Stress affects dopaminergic signaling pathways in Drosophila melanogaster. 1601 3


1 2 Next >>