IFN-γ facilitates NGF-induced neuronal differentiation in PC12 cells

Improta, Teresa; Salvatore, Anna Maria; Luzio, A. Di; Romeo, Giovanna; Coccia, Eliana M.; Calissano, Pietro

doi:10.1016/0014-4827(88)90342-4

Cited by 45 publications

(24 citation statements)

References 10 publications

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“…45,51 Although TPA cannot be utilized directly for therapeutic purposes, insight into the molecular signal pathways induced by TPA to restore growth control in tumor cells may generate new strategies for drug development. In addition to RA and TPA, IFN-␥ seems to synergize with or enhance the effect of a number of different signal pathways, such as vitamin D 3 , 42,45 TNF-␣ 60,63 and NGF, 64,65 all of which modulate differentiation in several cell types. The molecular basis for the effect of IFN-␥ on these distinct signal pathways is still unclear and will require further investigations, but may suggest that the different signal pathways converge at points that are under the influence of IFN-␥-induced signals.…”

Section: Discussionmentioning

confidence: 99%

Interferon-? cooperates with retinoic acid and phorbol ester to induce differentiation and growth inhibition of human neuroblastoma cells

et al. 2001

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The prognosis of patients with advanced stages of neuroblastoma with N-myc amplification remains poor despite escalated therapy, a situation that has called for alternative therapeutic approaches. Neuroblastoma cells, which represent immature peripheral neuronal cells, treated with certain physiologic and nonphysiologic agents such as retinoic acid (RA), phorbol esters and interferons (IFN) in vitro undergo cellular differentiation and stop to divide, a process that mimics normal neuronal development. Such "differentiation therapy" using RA after autologous bone marrow transplantation has recently given encouraging results in neuroblastoma patients with advanced disease. Considering approaches for improved differentiation therapy, we investi-

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Section: Discussionmentioning

confidence: 99%

Interferon-? cooperates with retinoic acid and phorbol ester to induce differentiation and growth inhibition of human neuroblastoma cells

et al. 2001

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“…It is of considerable interest that rat y-IFN, to which PC4 is related, has been recently shown to facilitate the NGF-'induced neuronal differentiation in PC12 cells, possibly via a more rapid entry into a Go state (36). Indeed, y-IFN is a lymphokine that inhibits cell proliferation to a greater extent, relative to its antiviral activity, than the other types of IFN (37).…”

Section: Resultsmentioning

confidence: 99%

Early gene regulation by nerve growth factor in PC12 cells: induction of an interferon-related gene.

Tirone

Shooter

1989

Proc. Natl. Acad. Sci. U.S.A.

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Nerve growth factor (NGF) induces the chromaffin cell line PC12 to differentiate into cells with many of the properties of sympathetic neurons. We investigated the early differentiative phase and identified a gene, PC4, rapidly and transiently induced by NGF in PC12 cells. PC4 cDNA is homologous to the partial sequence of a putative mouse Pinterferon and encodes a protein related to a lymphokine, the rat y-interferon protein.Nonetheless, PC4 appears devoid of antiviral activity. PC4 is expressed in proliferating and differentiating tissues, such as amnion, placenta, and brain at embryonic day 13.5. The relationship of PC4 to interferons and lymphokines suggests that it could play a role in regulating gene activity in the pathways induced by NGF.Nerve growth factor (NGF) was the first neurotrophic factor discovered in a class of molecules responsible for nervous system development and differentiation. NGF promotes the survival and the maintenance of sympathetic and some sensory neurons, such as those of the dorsal root ganglia and the trigeminal nuclei (1-3). NGF is also able to induce the chromaffin cells of the fetal adrenal medulla, a neural crest-derived tissue, to differentiate into sympathetic neurons (4), a phenomenon well represented in vitro in the clonal cell line PC12 (5). Since the precursors of chromaffin cells in vivo become determined toward the neuronal lineage before the onset of NGF influence (6), NGF can be regarded as a specific factor of commitment toward the sympathetic phenotype. The action of NGF is transcription-dependent (7). Genes regulated by NGF have been found, such as the protooncogenes c-fos and c-myc, whose mRNA levels are rapidly increased in PC12 cells by NGF (8) (HyClone). NGF (100 ng/ml) and N6,02'-dibutyryladenosine 3',5'-cyclic monophosphate (Bt2cAMP, 1 mg/ml, from Sigma) were added to cell cultures in the logarithmic phase of growth (about 75% confluent).RNA Isolation and Analysis. Cytoplasmic RNA was obtained from PC12 cells using the lysis method with 0.5% Nonidet P-40 (15) and was used for the construction of the cDNA libraries. Total cellular RNA was used for Northern blot analysis and was obtained by extraction in 4 M guanidine thiocyanate followed by centrifugation through a CsCl cushion (16). The RNA was separated electrophoretically on 1.2% agarose/2.2 M formaldehyde gels, transferred to nitrocellulose filters and hybridized to the PC4 probe, excised from the site Pst I in the pUC9 vector, and 32P-labeled with the random primers procedure (17). The hybridization was in 50% formamide, 5x SSC (lx SSC = 150 mM NaCl/15 mM sodium citrate, pH 7), 5 x Denhardt's solution (1 x Denhardt's solution = 1% Ficoll/1% polyvinylpyrrolidone/1% bovine serum albumin), 0.1% NaDodSO4, and 0.5 mg of salmon sperm DNA per ml for 20 hr at 42°C. The blots were then washed at 55°C in 0.1x SSC and 0.1% NaDodSO4.Construction and Screening of cDNA Libraries. In a first cDNA library of 8000 clones, the single-strand (ss-) and double-strand (ds-) cDNAs were synthesized from total cytoplas...

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“…Recent findings suggest that IFN-γ is an important mediator of neuronal plasticity, e.g. IFN-γ may enhance synaptogenesis, regulate synaptic plasticity and control neurogenesis (Brask et al, 2004;Vikman et al, 2001;Improta et al, 1988;Wong et al, 2004). It was recently reported that levels of IFN-γ are increased in circulating leukocytes of monkeys that had been maintained on a CR diet (Mascarucci et al, 2002).…”

Section: Cytokinesmentioning

confidence: 99%

Caloric restriction and intermittent fasting: Two potential diets for successful brain aging

Martin

Mattson

Maudsley

2006

Ageing Research Reviews

330

229

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The vulnerability of the nervous system to advancing age is all too often manifest in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In this review article we describe evidence suggesting that two dietary interventions, caloric restriction (CR) and intermittent fasting (IF), can prolong the health-span of the nervous system by impinging upon fundamental metabolic and cellular signaling pathways that regulate life-span. CR and IF affect energy and oxygen radical metabolism, and cellular stress response systems, in ways that protect neurons against genetic and environmental factors to which they would otherwise succumb during aging. There are multiple interactive pathways and molecular mechanisms by which CR and IF benefit neurons including those involving insulin-like signaling, FoxO transcription factors, sirtuins and peroxisome proliferatoractivated receptors. These pathways stimulate the production of protein chaperones, neurotrophic factors and antioxidant enzymes, all of which help cells cope with stress and resist disease. A better understanding of the impact of CR and IF on the aging nervous system will likely lead to novel approaches for preventing and treating neurodegenerative disorders.

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IFN-γ facilitates NGF-induced neuronal differentiation in PC12 cells

Cited by 45 publications

References 10 publications

Interferon-? cooperates with retinoic acid and phorbol ester to induce differentiation and growth inhibition of human neuroblastoma cells

Interferon-? cooperates with retinoic acid and phorbol ester to induce differentiation and growth inhibition of human neuroblastoma cells

Early gene regulation by nerve growth factor in PC12 cells: induction of an interferon-related gene.

Caloric restriction and intermittent fasting: Two potential diets for successful brain aging

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