Regulation of nerve growth factor biosynthesis by beta-adrenergic receptor activation in astrocytoma cells: a potential role of c-Fos protein.

Mocchetti, Italo; Bernardi, Maria A. De; Szekely, A M; Alho, Hannu; Brooker, Gary; Costa, E.

doi:10.1073/pnas.86.10.3891

Cited by 116 publications

(61 citation statements)

References 30 publications

(17 reference statements)

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“…The characteristic coupling of the ET A receptor to G protein subunits might explain the specificity of ET-1-induced NGF augmentation. In contrast to the present study, a previous study reported that the cAMP-PKA pathway was involved in β-adrenoreceptor-mediated NGF augmentation in astrocytoma cells (30). The finding that ET-1 does not induce NGF augmentation in cardiac fibroblasts suggests that the NGF induction pathway is mediated in a cell type-specific manner.…”

Section: Figurecontrasting

confidence: 99%

Endothelin-1 regulates cardiac sympathetic innervation in the rodent heart by controlling nerve growth factor expression

Ieda¹,

Fukuda²,

Hisaka³

et al. 2004

J. Clin. Invest.

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IntroductionCardiac tissues are extensively innervated by autonomic nerves. The cardiac sympathetic nerve plays an important role in modulating heart rate, conduction velocity, myocardial contraction, and relaxation. Although several molecules that regulate the development of the heart have been well characterized, little is known about the mechanism that regulates sympathetic innervation of the heart. The cardiac sympathetic nerve extends from the sympathetic neuron in stellate ganglia (SG), which is derived from the neural crest (1). Nerve growth factor (NGF) is a prototypic member of the neurotrophin family, members of which are critical for the differentiation, survival, and synaptic activity of the peripheral sympathetic and sensory nervous systems (2, 3). Levels of NGF expression within innervated tissues roughly correspond to innervation density (4). The volume of sympathetic ganglion is reduced by at least 80% at postnatal day 3 in mice with a disruption of the NGF gene. In mice that lack the NGF receptor TrkA, no neurons remain at postnatal day 9 (2). Deletion of a single copy of the NGF gene results in a 50% reduction in sympathetic neurons (5), while overexpression of NGF in the heart results in cardiac hyperinnervation and hyperplasia in SG neurons (6). These results demonstrate the importance of NGF in the regulation of sympathetic neuron development and innervation.In pathological states, NGF production in the heart is variable. In ischemic hearts, an increase in cardiac NGF leads to regeneration of sympathetic nerves (7,8). In a previous experiment, we found that NGF was upregulated in streptozotocin-induced diabetic murine hearts (9). In contrast, it was reported that NGF and sympathetic innervation were reduced in congestive heart failure (10). Despite their importance, the molecular mechanisms that regulate NGF expression and sympathetic innervation in the heart remain poorly understood.Endothelin-1 (ET-1) is believed to play a critical role in the pathogenesis of cardiac hypertrophy, hypertension, and atherosclerosis. Gene targeting of ET-1 and its receptor endothelin-A (ET A ) resulted in unexpected craniofacial and cardiovascular abnormalities. These phenotypes are consistent with interference of neural crest differentiation. The influence of ET-1 on neural crest development remains undetermined (11-13).We hypothesized that ET-1 could affect the induction of neurotrophic factors, and that its disruption might contribute to the immature development of neural crest-derived cells. In this study, we found ET-1-specific induction of NGF in cardiomyocytes, idenEndothelin-1 regulates cardiac sympathetic innervation in the rodent heart by controlling nerve growth factor expression The cardiac sympathetic nerve plays an important role in regulating cardiac function, and nerve growth factor (NGF) contributes to its development and maintenance. However, little is known about the molecular mechanisms that regulate NGF expression and sympathetic innervation of the heart. In an effort to identify regulato...

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Section: Figurecontrasting

confidence: 99%

Endothelin-1 regulates cardiac sympathetic innervation in the rodent heart by controlling nerve growth factor expression

Ieda¹,

Fukuda²,

Hisaka³

et al. 2004

J. Clin. Invest.

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“…The brain was removed, and brain areas were dissected on ice, frozen on dry ice, and stored at Ϫ80°C until further processing. NGF mRNA levels in mice were determined by Northern blot analysis as previously described (34,35). In brief, total RNA was extracted and size-fractionated by agarose/formaldehyde gel electrophoresis.…”

Section: Methodsmentioning

confidence: 99%

CAAT/Enhancer-binding Protein δ and cAMP-response Element-binding Protein Mediate Inducible Expression of the Nerve Growth Factor Gene in the Central Nervous System

McCauslin

Heath

Colangelo

et al. 2006

Journal of Biological Chemistry

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Nerve growth factor (NGF) synthesis in the rat cerebral cortex is induced by the ␤2-adrenergic receptor agonist clenbuterol (CLE). Because NGF is a crucial neurotrophic factor for basal forebrain cholinergic neurons, defining the mechanisms that regulate its transcription is important for developing therapeutic strategies to treat pathologies of these neurons. We previously showed that the transcription factor CCAAT/enhancer-binding protein ␦ (C/EBP␦) contributes to NGF gene regulation. Here we have further defined the function of C/EBP␦ and identified a role for cAMP response element-binding protein (CREB) in NGF transcription. Inhibition of protein kinase A in C6-2B glioma cells suppressed CLE induction of an NGF promoter-reporter construct, whereas overexpression of protein kinase A increased NGF promoter activity, particularly in combination with C/EBP␦. A CRE-like site that binds CREB was identified in the proximal NGF promoter, and C/EBP␦ and CREB were found to associate with the NGF promoter in vivo. Deletion of the CRE and/or C/EBP sites reduced CLE responsiveness of the promoter. In addition, ectopic expression of C/EBP␦ in combination with CLE treatment increased endogenous NGF mRNA levels in C6-2B cells. C/EBP␦ null mice showed complete loss of NGF induction in the cerebral cortex following CLE treatment, demonstrating a critical role for C/EBP␦ in regulating ␤2-adrenergic receptor-mediated NGF expression in vivo. Thus, our findings demonstrate a critical role for C/EBP␦ in regional expression of NGF in the brain and implicate CREB in CLE-induced NGF gene transcription.

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“…In astrocytes, PKC activation was associated with increased NGF, whereas increased cAMP levels did not affect NGF expression (48). In astrocytoma cells, c-fos activation increases NGF and inhibiting c-fos-reduced ␤-adrenergic receptor activation of NGF (49). In glioma cells PKA, PKC, or increased Ca 2ϩ mediates AP-1 (c-fos/c-jun) binding a consensus sequence in the NGF gene (50).…”

Section: Tlr2 Regulates Ngf Via Nf-bmentioning

confidence: 97%

Nerve Growth Factor Is Regulated by Toll-Like Receptor 2 in Human Intervertebral Discs

Krock

Currie

Weber

et al. 2016

Journal of Biological Chemistry

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Nerve growth factor (NGF) contributes to the development of chronic pain associated with degenerative connective tissue pathologies, such as intervertebral disc degeneration and osteoarthritis. However, surprisingly little is known about the regulation of NGF in these conditions. Toll-like receptors (TLR) are pattern recognition receptors classically associated with innate immunity but more recently were found to be activated by endogenous alarmins such as fragmented extracellular matrix proteins found in degenerating discs or cartilage. In this study we investigated if TLR activation regulates NGF and which signaling mechanisms control this response in intervertebral discs. TLR2 agonists, TLR4 agonists, or IL-1␤ (control) treatment increased NGF, brain-derived neurotrophic factor (BDNF), and IL-1␤ gene expression in human disc cells isolated from healthy, pain-free organ donors. However, only TLR2 activation or IL-1␤ treatment increased NGF protein secretion. TLR2 activation increased p38, ERK1/2, and p65 activity and increased p65 translocation to the cell nucleus. JNK activity was not affected by TLR2 activation. Inhibition of NF-B, and to a lesser extent p38, but not ERK1/2 activity, blocked TLR2-driven NGF up-regulation at both the transcript and protein levels. These results provide a novel mechanism of NGF regulation in the intervertebral disc and potentially other pathogenic connective tissues. TLR2 and NF-B signaling are known to increase cytokines and proteases, which accelerate matrix degradation. Therefore, TLR2 or NF-B inhibition may both attenuate chronic pain and slow the degenerative progress in vivo.

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Regulation of nerve growth factor biosynthesis by beta-adrenergic receptor activation in astrocytoma cells: a potential role of c-Fos protein.

Cited by 116 publications

References 30 publications

Endothelin-1 regulates cardiac sympathetic innervation in the rodent heart by controlling nerve growth factor expression

Endothelin-1 regulates cardiac sympathetic innervation in the rodent heart by controlling nerve growth factor expression

CAAT/Enhancer-binding Protein δ and cAMP-response Element-binding Protein Mediate Inducible Expression of the Nerve Growth Factor Gene in the Central Nervous System

Nerve Growth Factor Is Regulated by Toll-Like Receptor 2 in Human Intervertebral Discs

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