Tyrosine hydroxylase transcription depends primarily on cAMP response element activity, regardless of the type of inducing stimulus

Lewis‐Tuffin, Laura J.; Quinn, Patrick G.; Chikaraishi, Dona M.

doi:10.1016/j.mcn.2003.10.010

Cited by 98 publications

(91 citation statements)

References 69 publications

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“…To evaluate at the molecular level the action of NPY on TH gene transcription, we transfected the Y 1 -receptor-expressing cells SK-N-MC with a plasmid containing a 775-bp stretch of the rat TH promoter (Ϫ774 to the CTG initiation site). This stretch contained most transcription factorbinding sites, including the AP1, the SP1, the POU Oct, the GRE, and the two AP2 sites, as well as the cAMP response element sequence (Ϫ45 bp) that was shown to be the prime regulator of TH transcription (19). Incubation of transfected cells for 6 h with forskolin increased TH promoter-driven luciferase activity in a concentration-dependent way (Fig.…”

Section: Constitutive and Regulated Release Of Ne And Ep From Chromaffinmentioning

confidence: 98%

Deletion of the neuropeptide Y (NPY) Y ₁ receptor gene reveals a regulatory role of NPY on catecholamine synthesis and secretion

Cavadas

Céfaï

Rosmaninho‐Salgado

et al. 2006

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

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The contribution of neuropeptide Y (NPY), deriving from adrenal medulla, to the adrenosympathetic tone is unknown. We found that in response to NPY, primary cultures of mouse adrenal chromaffin cells secreted catecholamine, and that this effect was abolished in cultures from NPY Y1 receptor knockout mice (Y1؊͞؊). Compared with wild-type mice (Y1؉͞؉), the adrenal content and constitutive release of catecholamine were increased in chromaffin cells from Y 1؊͞؊ mice. In resting animals, catecholamine plasma concentrations were higher in Y1؊͞؊ mice. Comparing the adrenal glands of both genotypes, no differences were observed in the area of the medulla, cortex, and X zone. The high turnover of adrenal catecholamine in Y 1؊͞؊ mice was explained by the enhancement of tyrosine hydroxylase (TH) activity, although no change in the affinity of the enzyme was observed. The molecular interaction between the Y 1 receptor and TH was demonstrated by the fact that NPY markedly inhibited the forskolin-induced luciferin activity in Y 1 receptor-expressing SK-N-MC cells transfected with a TH promoter sequence. We propose that NPY controls the release and synthesis of catecholamine from the adrenal medulla and consequently contributes to the sympathoadrenal tone. (3,4). NPY is an important neurotransmitter of the sympathetic function that potentiates the catecholamine vasoconstrictor activity through the Y 1 receptor and exerts prejunctional inhibitory effects on NE release from the sympathetic nerve endings of the heart through the Y 2 receptor (5). In addition, the nerve terminals of parasympathetic neurons in the mouse heart possess Y 2 receptors, which, when activated, reduce acetylcholine release, also causing an inhibition of the parasympathetic nervous system (6). We have shown that NPY Y 1 knockout mice (Y 1 Ϫ͞Ϫ) lose their ability to potentiate NE-induced vasoconstriction and have normal blood pressure, probably indicating a minor role of NPY in the maintenance of blood pressure homeostasis (7). Recently, these mice were investigated for their cardiac sympathovagal balance in baseline conditions and during an acute social challenge. Reduced somatomotor activity during nonsocial challenges, lower heart rate in baseline conditions, and larger heart rate responsiveness during social defeat were reported (8). Besides its presence in nerve endings, NPY is produced by chromaffin cells of adrenal medulla of different species, including human (9). The mouse has higher adrenal NPY content than rat, pig, or humans (10, 11). The effect of NPY on the adrenal medulla is controversial. NPY stimulated catecholamine release from intact rat adrenal capsular tissue (12), although an inhibitory effect of NPY on catecholamine secretion in rat adrenomedullary primary cell cultures was also observed (13). Moreover, there is a weak inhibitory effect of NPY on NE and epinephrine (EP) release from bovine chromaffin cells, evoked by addition of a cholinergic agonist (14, 15). However, depending on the experimental conditions, conflicting results wer...

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Section: Constitutive and Regulated Release Of Ne And Ep From Chromaffinmentioning

confidence: 98%

Deletion of the neuropeptide Y (NPY) Y ₁ receptor gene reveals a regulatory role of NPY on catecholamine synthesis and secretion

Cavadas

Céfaï

Rosmaninho‐Salgado

et al. 2006

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

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“…These confounding issues inherent to the in vivo approach are less likely to be observed in the cultured model systems used in the present study. However, it is important to note that the TH gene promoter has a perfect consensus CRE just 35 bp upstream of the transcriptional start site and many studies have shown that this CRE is responsive to cAMP in pheochromocytoma, neuroblastoma, and cath.a cells (Kumer and Vrana, 1996;Lewis-Tuffin et al, 2004). Hence, the lack of an apparent transcriptional response in the cultured dopamine cell model systems is very surprising and how these results relate to the response observed under in vivo conditions requires further investigation.…”

Section: Camp-mediated Activation Of Th Mrna Translation 1825mentioning

confidence: 99%

“…The cells were cultured as described by Choi et al (1992) in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum (Invitrogen) in an atmosphere of 95% air and 5% CO 2 . PC18 and cath.a cells were cultured as described previously (Tank et al, 1986;Lewis-Tuffin et al, 2004).…”

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confidence: 99%

Activation of Tyrosine Hydroxylase mRNA Translation by cAMP in Midbrain Dopaminergic Neurons

Chen¹,

Lu²,

Radcliffe³

et al. 2008

Mol Pharmacol

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During prolonged stress or chronic treatment with neurotoxins, robust compensatory mechanisms occur that maintain sufficient levels of catecholamine neurotransmitters in terminal regions. One of these mechanisms is the up-regulation of tyrosine hydroxylase (TH), the enzyme that controls catecholamine biosynthesis. In neurons of the periphery and locus coeruleus, this up-regulation is associated with an initial induction of TH mRNA. In contrast, this induction either does not occur or it is nominal in mesencephalic dopamine neurons. The reasons for this lack of compensatory TH mRNA induction remain obscure, because so little is known about the regulation of TH expression in these neurons. In this study, we test whether activation of the cAMP signaling pathway regulates TH gene expression in two rodent models of midbrain dopamine neurons, ventral midbrain organotypic slice cultures and MN9D cells. Our results demonstrate that elevation of cAMP leads to induction of TH protein and TH activity in both model systems; however, TH mRNA levels are not up-regulated by cAMP. The induction of TH protein is the result of a novel post-transcriptional mechanism that activates TH mRNA translation. This translational activation is mediated by sequences within the 3Ј untranslated region (UTR) of TH mRNA. Our results support a model in which cAMP induces or activates trans-factors that interact with the TH mRNA 3ЈUTR to increase TH protein synthesis. An understanding of this novel regulatory mechanism may help to explain the control of TH gene expression and consequently dopamine biosynthesis in midbrain neurons under different physiological and pathological conditions.

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“…Their role in the regulation of TH gene expression in the response to nicotine has not been well studied. Use of various chimeras of transcription factors with Gal4 indicated that in conjunction with CREBbinding protein, they can mediate CRE-dependent transcriptional activation of the TH promoter (19,20). ATF-1 was only marginally effective in increasing TH promoter activity, suggesting that it does not play a major role in the regulation of TH gene expression.…”

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confidence: 99%

Prolonged Activation of cAMP-response Element-binding Protein and ATF-2 Needed for Nicotine-triggered Elevation of Tyrosine Hydroxylase Gene Transcription in PC12 Cells

Gueorguiev

Cheng

Sabban

2006

Journal of Biological Chemistry

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Phosphorylation (P-) of cAMP-response element-binding protein (CREB) by protein kinase A or mitogen-activated protein kinases was implicated in mediating the increased tyrosine hydroxylase (TH) gene expression after prolonged exposure to nicotine in vivo and in cell culture. We examined the time course and signaling pathways for phosphorylation of CREB and possible involvement of ATF-2. Treatment of PC12 cells with 200 M nicotine triggered rapid but transient elevation of P-CREB followed by a second sustained rise after 2-5 h of continuous nicotine. In contrast, ERK1/2 was only phosphorylated with short term nicotine exposure. MEK inhibitor U0126 abolished nicotine-induced rise in P-ERK1/2, but not P-CREB, nor did it inhibit nicotine-evoked elevation in TH promoter activity, indicating that ERK1/2 was not needed for induction of TH gene expression by nicotine. In contrast, protein kinase A inhibitor H-89 or Ca 2؉ / calmodulin-activated protein kinase inhibitor KN-93 reduced the nicotine-triggered rise in P-CREB and TH promoter activity. There was a delayed elevation of P-ATF-2 after 1 h of nicotine treatment, accompanied by increased ATF-2 protein. Upstream kinase JNK, but not p38, was phosphorylated especially after 5 min to 2 h of nicotine exposure. To examine the requirement for CREB and ATF-2, cells were transfected with dominant negative forms of ATF-2 or CREB. Both reduced the basal TH promoter activity and the response to nicotine. Knockdown of ATF-2 or CREB with siRNA did not alter basal TH promoter activity or mRNA but greatly attenuated the response to nicotine. The results suggest that both ATF-2 and CREB mediate activation of TH gene transcription by nicotine.Administration of nicotine in vivo and in cell culture triggers increased expression of a number of genes related to neurosecretion including the catecholamine biosynthetic enzymes. These changes in gene expression may be involved in neurochemical and cardiovascular effects of smoking. Nicotine is a potent sympathomimetic agent, and its administration, in doses similar to those obtained in smoking, increases heart rate and systolic and diastolic blood pressure in humans and many animal species (for review, see Ref. 1). These cardiovascular effects are largely attributed to the direct stimulation of release of catecholamines, epinephrine and norepinephrine, from the adrenal medulla and peripheral sympathetic nerve endings (2-4). In this regard a polymorphism in the gene for tyrosine hydroxylase (TH), 2 the rate-limiting enzyme in catecholamine biosynthesis, has been associated with tobacco use (5).Transcriptional mechanisms are at least partially responsible for the nicotine triggered changes in TH gene expression. The response of TH to nicotine has been proposed to be mediated by CREB. Nicotine treatment both in vivo and in vitro induces phosphorylation of CREB (6 -8).The cAMP/calcium response element (CRE/CaRE) in the TH promoter is required for its transcriptional activation by nicotine in PC12 cells (6). CREB is activated through the phosphor...

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Tyrosine hydroxylase transcription depends primarily on cAMP response element activity, regardless of the type of inducing stimulus

Cited by 98 publications

References 69 publications

Deletion of the neuropeptide Y (NPY) Y ₁ receptor gene reveals a regulatory role of NPY on catecholamine synthesis and secretion

Deletion of the neuropeptide Y (NPY) Y ₁ receptor gene reveals a regulatory role of NPY on catecholamine synthesis and secretion

Activation of Tyrosine Hydroxylase mRNA Translation by cAMP in Midbrain Dopaminergic Neurons

Prolonged Activation of cAMP-response Element-binding Protein and ATF-2 Needed for Nicotine-triggered Elevation of Tyrosine Hydroxylase Gene Transcription in PC12 Cells

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Tyrosine hydroxylase transcription depends primarily on cAMP response element activity, regardless of the type of inducing stimulus

Cited by 98 publications

References 69 publications

Deletion of the neuropeptide Y (NPY) Y 1 receptor gene reveals a regulatory role of NPY on catecholamine synthesis and secretion

Deletion of the neuropeptide Y (NPY) Y 1 receptor gene reveals a regulatory role of NPY on catecholamine synthesis and secretion

Activation of Tyrosine Hydroxylase mRNA Translation by cAMP in Midbrain Dopaminergic Neurons

Prolonged Activation of cAMP-response Element-binding Protein and ATF-2 Needed for Nicotine-triggered Elevation of Tyrosine Hydroxylase Gene Transcription in PC12 Cells

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Deletion of the neuropeptide Y (NPY) Y ₁ receptor gene reveals a regulatory role of NPY on catecholamine synthesis and secretion

Deletion of the neuropeptide Y (NPY) Y ₁ receptor gene reveals a regulatory role of NPY on catecholamine synthesis and secretion