Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tubby mouse is characterized by an autosomal recessive mutation which results in the development of maturity-onset obesity and sensorineural hearing loss and retinal degeneration. Although the tubby mutation which leads to a splicing defect of the tub gene has been identified recently, the mechanism by which it causes the obesity syndrome has not been established. In this study, the potential dysfunction of several hypothalamic neuroendocrine pathways involved in the central regulation of energy metabolism was investigated in tubby mice. In comparison with the wild-type controls, a significant reduction (20%) of pro-opiomelanocortin (POMC) mRNA expression was observed in the arcuate nucleus (ARC) of the mature, obese but not in the juvenile, non-obese tubby mice. Similarly, an age and body mass-dependent induction (about 30-fold) of neuropeptide Y (NPY) mRNA was observed in the dorsomedial (DMH) and ventromedial (VMH) hypothalamic nuclei of the tubby mice. However, NPY mRNA in the ARC was decreased by approximately 30 to 40% in both juvenile and mature tubby mice. The hypothalamic expression patterns of corticotropin releasing hormone (CRH) and the long form leptin receptor (OB-Rb) were not significantly altered in the mutant mice. These results suggest that the altered hypothalamic POMC and/or NPY functions may be important contributing factors for the development of obesity in this animal model.
Brain Res Mol Brain Res 1998 Aug 31
PMID:Evidence of altered hypothalamic pro-opiomelanocortin/ neuropeptide Y mRNA expression in tubby mice. 972 27

Neurones of the suprachiasmatic nucleus constitute the mammalian circadian clock which receives photic information via the retino-hypothalamic tract and to some extent non-photic information via the geniculo-hypothalamic tract. The majority of neurones in the geniculo-hypothalamic tract contains neuropeptide Y and both in vitro and in vivo physiological experiments have demonstrated that neuropeptide Y administered directly into the suprachiasmatic nucleus has the capacity to phase-shift the endogenous circadian rhythm of these neurones. The recent cloning of multiple mammalian neuropeptide Y receptors enabled us to perform an in situ hybridization histochemical study identifying expression of distinct neuropeptide Y receptor encoding mRNAs in the suprachiasmatic nucleus. It was seen that Y1 and Y5 receptor mRNA is highly expressed in neurones of the ventrolateral portion of the suprachiasmatic nucleus while neither Y2 nor Y4 receptor mRNA could be detected in the nucleus. These experiments demonstrate that post-synaptic neuropeptide Y mediated events in the suprachiasmatic nucleus are likely to be mediated by either of these receptors.
Brain Res Mol Brain Res 1998 Sep 18
PMID:Distribution of neuropeptide Y receptor expression in the rat suprachiasmatic nucleus. 974 10

The functional properties of the isolated porcine and bovine central adrenomedullary veins were compared, with emphasis on the active tension responses to high K+, endothelin-1 (ET-1) and neuropeptide Y (NPY). In the porcine vein, the contraction evoked by ET-1 was 4--5-fold higher than with high K+, as in the bovine vein. The potencies for ET-1 were similar in ring and strip preparations of the porcine vein, with EC50 values 5--7-fold higher than in the bovine vein. In preparations previously exposed to ET-1 the contractions evoked by high K+ and NPY were potentiated and facilitated, respectively,. However, only in the porcine vein was the ET-1 contraction sustained. This contraction was effectively relaxed by milrinone, indicating a role for cGMP inhibited cyclic nucleotide phosphodiesterase in the sustained contraction. Caffeine and forskolin were also effective relaxants of contractions evoked by ET-1 in both veins, suggesting relaxation by elevated levels of cAMP. The K(+)-contracted porcine, but not bovine, vein was relaxed by acetylcholine (ACh) and vasointestinal polypeptide in a concentration-dependent manner, indicating species differences with respect to signal transduction leading to increases in cyclic nucleotides. In conclusion, these results demonstrate that ET-1 is the main constrictor of the porcine central adrenomedullary vein, with significant species differences in mode of contraction and relaxation. These findings suggest roles for the endogeneously released ET-1 and NPY in regulation of venous contractility within the adrenal gland of mammals.
Comp Biochem Physiol A Mol Integr Physiol 1998 Jul
PMID:The adrenomedullary venous vasculature as a target for endothelins: comparison of the porcine and bovine central adrenomedullary veins. 978 29

The present study investigated the regional distribution of putative 'food-intake'-related neuropeptide Y Y5 receptor gene using cRNA in situ hybridization in various regions of the normal control post-mortem human brain. Interestingly, significant levels of Y5 receptor expression were detected in the hypothalamus; the arcuate nucleus being particularly enriched compared to other hypothalamic nuclei. Surprisingly, strong hybridization signals were also noted in the stratum granulosum of the dentate gyrus contrasting with lower levels of Y5 receptor transcripts in other regions of the hippocampal formation. The cerebral cortex, basal ganglia and thalamus were not enriched with Y5 receptor mRNA. It thus appears that the expression of the Y5 receptor gene in the human brain is rather restricted with enrichment in areas consistent with the involvement of this receptor type in the modulation of appetite and seizures.
Brain Res Mol Brain Res 1998 Oct 30
PMID:Discrete distribution of the neuropeptide Y Y5 receptor gene in the human brain: an in situ hybridization study. 979 64

Sucrose gradient centrifugation combined with electron microscopy revealed that undifferentiated SH-SY5Y cells contain predominantly one population of noradrenaline containing vesicles, i.e. large dense cored vesicles. These vesicles have been purified approximately twenty times using sucrose/D2O gradients. Electron microscopy of sucrose/D2O fractions confirms that large dense cored vesicles are enriched in the fractions containing predominantly dopamine- -hydroxylase, chromogranin A, noradrenaline and neuropeptide Y. The membranes of these vesicles contain the typical large dense cored vesicle markers dopamine- -hydroxylase, synaptotagmin, cytochrome b561 and rab 3. Stimulation of SH-SY5Y cells with carbachol and KCl shows that noradrenaline and neuropeptide Y are released in the same proportion as stored in the large dense cored vesicles. The immuno-blot pattern and intensity of chromogranin A and chromogranin B present in large dense cored vesicles and in the released material were definitely the same. This suggests that noradrenaline and the proteins/peptides are released in the same molar stoichiometry as they are stored in large dense cored vesicles. These data provide for the first time experimental evidence that the neuroblastoma cell line SH-SY5Y contains functionally active large dense cored vesicles similar to those of sympathetic neurons and indicate that this cell line is a suitable experimental cell model to study the exocytotic pathway of large dense cored vesicles.
Int J Mol Med 1998 Jan
PMID:The storage of noradrenaline, neuropeptide Y and chromogranins in and stoichiometric release from large dense cored vesicles of the undifferentiated human neuroblastoma cell line SH-SY5Y. 985 6

Bacterial-derived products [e.g., lipopolysaccharide (LPS) from Gram-negative and muramyl dipeptide (MDP) from Gram-positive bacteria] are proposed to play a pivotal role in the generation of neurological and neuroinflammatory/immunological responses during bacterial infections of the nervous system. LPS and MDP may act through cytokines; cytokine-neuropeptide interactions may also be involved. Here, we investigated cytokine and neuropeptide mRNA profiles in specific brain regions in response to the intracerebroventricular administration of LPS and MDP. IL-beta1 system components (ligand, signalling receptor, receptor accessory proteins, receptor antagonist), TNF-alpha, TGF-beta1, glycoprotein 130 (IL-6 receptor signal transducer), OB protein (leptin) receptor, neuropeptide Y, Y5 receptor, and pro-opiomelanocortin (opioid peptide precursor) mRNAs were analyzed. The same brain region sample was assayed for all components. LPS and MDP administration induced significantly different behavioral and molecular profiles. LPS was significantly more potent than MDP in inducing anorexia and in up-regulating pro-inflammatory cytokines (IL- beta1 and TNF-alpha mRNAs in the cerebellum, hippocampus and hypothalamus; MDP was more potent in up-regulating anti-inflammatory cytokine (IL-1 receptor antagonist and TGF-beta1) mRNAs. LPS and MDP also modulated hypothalamic IL-1 receptor mRNA components, but did not affect any of the neuropeptide-related components examined. The results suggest that the magnitude of neurological manifestations induced by LPS and MDP may involve the ratio between stimulatory and inhibitory cytokines, and this ratio may have implications for the neuroinflammatory/neurotoxic events associated with bacterial infections of the central nervous system.
Int J Mol Med 1998 Feb
PMID:Gram-negative and gram-positive bacterial products induce differential cytokine profiles in the brain: analysis using an integrative molecular-behavioral in vivo model. 985 41

The gene expression of prepro-orexin, the precursor of orexin-A and orexin-B which are hypothalamic pepetides that are associated with feeding behavior, were examined in control (C57B1/6J) and obese (ob/ob and db/db) mice using in situ hybridization histochemistry. Orexins are identical with hypocretins that have been identified by directional tag PCR subtractive hybridization method. In situ hybridization histochemistry revealed that the expression of the prepro-orexin gene was significantly decreased in ob/ob and db/db mice compared with control mice. The gene expression of neuropeptide Y (NPY), a potent feeding stimulant, is known to be increased in ob/ob and db/db mice. The expression of the NPY gene in the arcuate nucleus was increased remarkably in ob/ob and db/db mice compared to that of control mice. An immunohistochemical study showed that orexin-A and orexin-B immunoreactive neurons exhibited in the lateral and posterior hypothalamic areas and the perifornical nucleus were distributed similarly in control, ob/ob and db/db mice. These results suggest that the regulatory mechanism of orexins/hypocretins may be different from that of NPY in genetically obese mice.
Brain Res Mol Brain Res 1999 Feb 19
PMID:Down regulation of the prepro-orexin gene expression in genetically obese mice. 1003 3

The autonomic innervation of the canine heart develops with considerable regional asymmetry during the early neonatal period. To examine the development of the peptidergic component of the innervation, 28 mongrel puppies 1-6 weeks of age from five litters were studied at weekly intervals. Four of the mothers were also studied as adult and breed controls. Tissue neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) concentrations were determined by radioimmunoassay in myocardial specimens obtained from several specific sites of the cardiac chambers and from the proximal coronary arteries. Data were analysed according to age, cardiac chamber/vessel, gender and individual litter. In general, NPY concentrations in pg/mg protein were six- to eight-fold higher than those of VIP. Also concentrations for both peptides were about two-fold higher in the coronary arteries than the myocardium and differed among chambers, being higher and similar in the atria and lower in the ventricles, particularly for NPY. No gender differences were identified. Concentrations varied among litters, but the developmental pattern was similar with the highest peptide concentrations identified in the first and fourth week. Whereas the differences among chambers may also reflect differing rates of developmental increase of myocardial mass, the pattern corresponds only in part to previously identified functional changes in sympathetic innervation since, in contrast to previous findings, high NPY concentrations in the first 2 weeks suggest anatomically advanced innervation.
J Mol Cell Cardiol 1999 Jan
PMID:Postnatal development of peptidergic innervation of the canine heart. 1007 29

Anorexia and body weight loss are characteristic of many diseases, including cancer and AIDS. Recent studies indicate that inflammatory cytokines, such as interleukin 1, the interleukin 6 subfamily and tumor necrosis factor, induce anorexia and cachexia by inhibiting the normal adaptive feeding response to energy deficits. Here, I discuss the evidence for and against a central role for neuropeptide Y and leptin in anorexia and cachexia.
Mol Med Today 1999 Feb
PMID:Neuropeptide Y: a key molecule in anorexia and cachexia in wasting disorders? 1020 Sep 49

Young and old Long-Evans rats respond with fevers of equal magnitude and duration to the brain administration of interleukin-1beta (IL-1beta). Here, we characterized brain regional mRNA expression of cytokine and neuropeptide components in response to the brain administration of IL-1beta. We used specific and highly sensitive RNase protection assays to determine mRNA changes for IL-1beta, IL-1 receptor type I (IL-1RI), IL-1R accessory proteins I and II (IL-1R AcP I and II), IL-1 receptor antagonist (IL-1Ra), transforming growth factor-beta1 (TGF-beta1), glycoprotein 130 (gp 130), leptin receptor (OB-R), neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) in the cerebellum, parieto-frontal cortex, hippocampus, hypothalamus, and midbrain of male young (3-5 months) and old (24-26 months) Long-Evans rats. In both young and old rats, IL-1beta induced a significant up-regulation of cerebellar IL-1Ra, IL-1RI, and TGF-beta1 mRNAs; hippocampal TGF-beta1 mRNA; hypothalamic IL-1beta, IL-1Ra, TGF-beta1, and gp 130 mRNAs; and midbrain IL-1beta and TGF-beta1 mRNAs. There were no age-related differences in any cytokine mRNA levels under basal or IL-1beta-stimulated conditions. Levels of hypothalamic POMC mRNA were different between age groups under basal and stimulated conditions. IL-1R AcP I and leptin receptor did not change in any brain region from either young or old rats, suggesting specificity of transcriptional changes. The data show that old Long-Evans rats are not defective in their capacity to develop an appropriate cytokine response to the brain administration of IL-1beta. The implications of these findings for neuroimmunological-neuroinflammatory and neurotoxic/neurodegenerative processes are discussed.
Brain Res Mol Brain Res 1999 Jun 18
PMID:Basal and IL-1beta-stimulated cytokine and neuropeptide mRNA expression in brain regions of young and old Long-Evans rats. 1038 47


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