neuropeptide-y and Glioma

Topics: Adrenal Gland Neoplasms; Animals; Glioma; Humans; Neuropeptide Y; Pheochromocytoma; Tissue Distribution

Chemokines expressed in neurons are important mediators in neuron-neuron and neuron-glia signaling. One of these chemokines is CCL21 that activates microglia via the chemokine receptor CXCR3. As neurons also express CXCL10, a main ligand for CXCR3, we have thus investigated in detail the expression pattern of CXCL10 in neurons. We show that CXCL10 is constitutively expressed by neurons, is stored in large dense-core vesicles and is not regulated by neuronal injury or stress. Neuronal CXCL10 release occurred constitutively at low level. In vivo CXCL10 expression was found in the developing brain at various embryonic stages and its peak expression correlates with the presence of CD11b- and GFAP-positive cells expressing CXCR3. These results suggest a possible role of neuronal CXCL10 in recruitment and homing of glial cells during embryogenesis.

Topics: Amyloid beta-Peptides; Animals; CD11b Antigen; Cells, Cultured; Cerebral Cortex; Chemokine CXCL10; Coculture Techniques; Embryo, Mammalian; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Gene Expression Regulation; Gene Expression Regulation, Developmental; Glial Fibrillary Acidic Protein; Glioma; Glutamic Acid; Green Fluorescent Proteins; Humans; Immunoprecipitation; Lipopolysaccharides; Mice; Microscopy, Immunoelectron; Neuroblastoma; Neuroglia; Neurons; Neuropeptide Y; Peptide Fragments; RNA, Messenger; Sodium Azide; Sodium Chloride; Synaptic Vesicles; Time Factors; Transfection; Vesicle-Associated Membrane Protein 2

We detected distinct plasma concentration profiles of S100B, neuropeptide Y, and secretagogin in 3 of 191 patients enrolled in a previous study investigating brain-tissue-related markers in the blood of patients with atrial fibrillation. Intriguingly, 2 of these 3 patients, both of whom were without neurological symptoms at the time of blood sampling, were diagnosed with malignant glioma (MG) approximately 1 year later. To our knowledge, this is the first report indicating that distinct blood biomarker profiles may be detected long before clinical manifestation of MG.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers, Tumor; Brain Neoplasms; Calcium-Binding Proteins; Female; Glioma; Humans; Male; Middle Aged; Nerve Growth Factors; Neuropeptide Y; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Secretagogins; Young Adult

We have investigated the expression of neuropeptide Y (NPY) in C6 glioma cells after the glutamatergic stimulation by the in situ RT-PCR and immunocytochemical techniques. The expression of NPY mRNA correlated well with immunocytological findings in each series of experiments. NPY protein expression was enhanced by glutamate (1, 10, 50, 100 microM, and 1 mM) dose-dependently, and its expression was slightly increased by N-methyl-D-aspartate (NMDA; 1, 10, 100, 500 microM, and 1 mM) and kainic acid (1, 10, 100, 300 microM, and 1 mM). We pretreated the cells with dopamine, haloperidol, pentylenetetrazol, and muscimol before each stimulation. The pentylenetetrazol and muscimol did not significantly alter the patterns of NPY expression induced by the glutamatergic stimulation. On the other hand, the dopamine and haloperidol pretreatment significantly elevated the levels of NPY expression that were induced by NMDA and kainic acid. Our results indicate that NPY release is closely related to glutamatergic stimulation, and it could be dynamically mediated by GABAergic and dopaminergic costimulation.

Topics: Animals; Dopamine; Gene Expression Regulation, Neoplastic; Glioma; Glutamic Acid; Haloperidol; Kainic Acid; Muscimol; Neuropeptide Y; Pentylenetetrazole; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transcription, Genetic; Tumor Cells, Cultured

Several studies have shown that neuropeptide Y (NPY) is involved in the stimulation of gonadotropin hormone releasing hormone (GnRH) and luteinizing hormone (LH) secretion and that these effects are modulated by gonadal steroid feedback. The NPY regulation of GnRH release is probably mediated by the activation of the Y(1) receptor subtype. In this study we examined the regulation of the Y(1) receptor gene transcription by estrogens in transiently transfected NG108-15 neuroblastoma glioma cells. A chimeric plasmid containing the murine Y(1) receptor promoter fused to the firefly luciferase reporter gene was induced by approximately 2-fold in response to 17 beta-estradiol treatment. The estrogen-mediated enhancement of luciferase activity was dose-dependent, blocked by the estrogen receptor (ER) antagonist ICI 182,780, and was strictly dependent on the presence of ER alpha, since it occurred only in NG108-15 cells cotransfected with an expression vector for the human ER. Mutational analysis was performed to investigate whether the hemipalindromic estrogen-responsive elements (EREs) flanking the Y(1) receptor gene are responsible for conferring estradiol inducibility to the Y(1) receptor gene promoter. Mutation of the ERE1 half site at position -932, or mutation of the ERE2 half site at position -809, relative to the ATG, failed to affect the 17 beta-estradiol-mediated enhancement of luciferase activity. Conversely, mutation of both ERE1 and ERE2 half sites completely abolished activation of luciferase activity induced by estrogen. We also examined whether 17 beta-estradiol stimulates the transcriptional activity of the Y(1) receptor gene by binding to ER beta. Results demonstrated that luciferase activity was not modulated by estrogens when cells were transfected with the expression plasmid bearing the human ER beta. Moreover coexpression of both ER alpha and ER beta completely abolished the estrogen-induced activation of luciferase activity observed in the presence of ER alpha. Our data suggest that estrogens activate Y(1) receptor gene transcription possibly via a direct interaction of ER alpha with the hemipalindromic EREs flanking the Y(1) receptor gene.

Topics: Animals; DNA Primers; Estradiol; Estrogen Receptor alpha; Gene Expression Regulation; Genes, Reporter; Glioma; Luciferases; Mice; Mutagenesis; Neuroblastoma; Neuropeptide Y; Promoter Regions, Genetic; Rats; Receptors, Estrogen; Receptors, Neuropeptide Y; Transcription, Genetic; Transfection; Tumor Cells, Cultured

We have investigated the presence and expression of laminin and neuropeptide Y (NPY) in several NG108-15 cell lines transfected with synapsin Ib, IIa, or IIb. The content of laminin, a basal membrane glycoprotein that promotes adhesion and induces neurite out-growth and neuronal differentiation, was increased in all transfected cell lines examined. In cells that were chemically differentiated with prostaglandin E1 plus 3-isobutyl-1-methylxanthine, laminin levels were increased even further. The content of NPY, suggested to be a neurotransmitter/neuromodulator in peripheral sympathetic neurons as well as in central neurons, was also increased in all transfected cell lines examined. Immunohistochemical analysis combined with confocal laser microscopy showed that NPY staining was granular and very often enriched in neuritic varicosities. The distribution and the staining pattern of NPY were consistent with storage of NPY in large dense-cored vesicles. The results indicate that, in differentiated neurons, the synapsins increase the levels of a neuropeptide transmitter stored in large dense-cored vesicles and of an extracellular matrix protein associated with neuronal maturation.

Topics: Glioma; Hybrid Cells; Immunohistochemistry; Laminin; Neuroblastoma; Neuropeptide Y; Synapsins; Transfection; Tumor Cells, Cultured

Neuropeptide Y (NPY) was continuously administered to Wistar rats in the normal and glioma bearing conditions intracarotidly via the external carotid artery and local cerebral blood flow (LCBF) was measured by a [14C] iodoantipyrine technique. In the normal rats, the LCBF at the injecting side of NPY markedly reduced in 2 minutes after beginning of drug administration. In glioma-bearing rats, LCBF in the cerebral cortex and caudate nucleus reduced to the same level as normal rats. However reduction of LCBF in the tumor was not significantly different from that of ipsilateral cortex and caudate nucleus. The results of this study suggest that flow moduration by NPY injection increases delivery of intra-carotid administered anticancer drugs to the brain tumor with concomitant decrease of neurotoxicity to the normal brain.

Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Carotid Artery, External; Cerebrovascular Circulation; Drug Delivery Systems; Glioma; Injections, Intra-Arterial; Male; Neuropeptide Y; Rats; Rats, Wistar

High concentrations of a newly-identified biologically potent peptide, neuropeptide Y, have been demonstrated in 3 related mouse neuroblastoma-derived clonal cell lines, N18TG2 0.35 pmol/mg protein, NG108-15 0.44 pmol/mg protein and NCB-20 0.39 pmol/mg protein. The NG108-15 cell line was chosen for further evaluation. Dexamethasone (10 microM) and nerve growth factor (10 ng/ml) resulted in a 2-fold increase in cellular neuropeptide Y concentrations. The response to dexamethasone was demonstrated to be dose-dependent. Exposure to both agents in combination resulted in a more than additive effect, indicating synergism.

Topics: Animals; Cell Line; Chromatography, High Pressure Liquid; Dexamethasone; Glioma; Hybrid Cells; Kinetics; Mice; Nerve Growth Factors; Nerve Tissue Proteins; Neuroblastoma; Neuropeptide Y; Rats