Promoter elements and second messenger pathways involved in transcriptional activation of tyrosine hydroxylase by ionomycin

Nankova, Bistra B.; Hiremagalur, Bhargava; Menezes, Ana Catarina; Zeman, Richard J.; Sabban, Esther L.

doi:10.1016/0169-328x(95)00201-3

Cited by 37 publications

(32 citation statements)

References 43 publications

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“…The CRE (position Ϫ45-38) site within the TH promoter is present in our plasmid and may mediate, at least in part, the forskolin-triggered TH promoter activation. In addition, both the CRE and AP1 (Ϫ201-195) sites appear to mediate PKC-mediated TH promoter activation (35,(45)(46)(47)(48)(49). Our observed impairment of forskolin- induced TH promoter activation by the PKA inhibitor, CalC, further confirms the reported role of PKA-mediated cAMPdependent signaling in this process.…”

Section: Discussionsupporting

confidence: 84%

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: Discussionsupporting

confidence: 84%

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 TH CRE2 is not capable of independently responding to Ca 2ϩ influx. Induction of TH AP1 Complex Formation after Depolarization of PC12 Cells-The involvement of the CRE in Ca 2ϩ -mediated TH gene regulation has been previously demonstrated (24,25). However, the present study is the first to demonstrate directly the involvement of the TH AP1 site in response to Ca 2ϩ influx.…”

Section: Evaluation Of Promoter Elements Involved In Depolarizationmesupporting

confidence: 44%

“…Using deletion analysis, they have also reported that promoter elements upstream of the CRE do not apparently participate in the response of the TH gene promoter to Ca 2ϩ . Recently, these results have been extended using TH gene constructs with site-directed mutations (25). Results from these studies suggest that the TH AP1 site is not involved in Ca 2ϩ -mediated TH gene regulation.…”

mentioning

confidence: 97%

Tyrosine Hydroxylase Gene Promoter Activity Is Regulated by Both Cyclic AMP-responsive Element and AP1 Sites following Calcium Influx

Nagamoto-Combs¹,

Piech²,

Best³

et al. 1997

Journal of Biological Chemistry

104

125

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Membrane depolarization of PC12 cells using 50 mM KCl leads to induction of tyrosine hydroxylase (TH) mRNA. This induction of TH mRNA is apparently due to increased TH gene promoter activity mediated by the influx of Ca 2؉ . In PC12 cells transiently transfected with a chimeric gene expressing chloramphenicol acetyltransferase (CAT) driven by the proximal TH gene 5 -flanking region, 50 mM KCl increases TH gene promoter activity 3-4-fold. Promoter analysis utilizing TH-CAT constructs containing mutagenized sequences indicates that this response to the depolarization-mediated influx of Ca 2؉ is primarily dependent on both the TH cAMPresponsive element (CRE) and TH activating protein-1 (AP1) site. Minimal promoter constructs that contain a single copy of either the TH CRE or TH AP1 site fused upstream of the TH gene basal promoter are only modestly responsive or nonresponsive, respectively, to depolarization. However, both these constructs are strongly responsive to the calcium ionophore, A23187. Gel shift assays indicate that TH AP1 complex formation is dramatically increased after treatment with either 50 mM KCl or A23187. Using antibodies to transcription factors of the Fos and Jun families, we show that the nuclear proteins comprising the inducible TH AP1 complex include c-Fos, c-Jun, JunB, and JunD. In cAMP-responsive element binding protein (CREB)-deficient cell lines that express antisense RNA complementary to CREB mRNA, the response of the TH gene promoter to cyclic AMP is dramatically inhibited, but the response to A23187 remains robust. This result indicates that transcription factors other than CREB can participate in the Ca 2؉ -mediated regulation of the TH gene. In summary, our results support the hypothesis that regulation of the TH gene by Ca 2؉ is mediated by mechanisms involving both the TH CRE and TH AP1 sites and that transcription factors other than or in addition to CREB participate in this response.Biosynthesis of the catecholamines is tightly regulated by the activity of the rate-limiting enzyme, tyrosine hydroxylase (TH 1 ; EC 1.14.16.2). Experimental manipulations that lead to long-term stimulation of catecholaminergic cells in sympathetic ganglia and adrenal medulla are associated with increases in TH gene expression (1-8). The mechanisms responsible for regulation of the TH gene are complex and have not been fully elucidated. Cultured rat pheochromocytoma cells have been used extensively to study the underlying mechanisms for TH gene regulation. Using this model system, a number of laboratories have shown that cAMP analogs (9 -11), active phorbol esters (12), and glucocorticoids (8 -10, 13) induce TH mRNA, stimulate TH gene transcription rate, and/or activate TH gene promoter activity. These results are consistent with the hypothesis that protein kinase A, protein kinase C, and glucocorticoid receptors participate in signaling pathways that regulate the TH gene.Treatments that lead to increased intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) also increase expression of the TH gene. Studie...

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“…4, lane 13), and an anti-ATF-2 antibody supershifted Band 1 to Band A (Fig. 4, lane 14), indicating that Bands 1 and 2 represented complexes containing ATF-2 and CREB, respectively. Since ATF-2 was reported to bind to CRE as a homodimer or as a heterodimer with c-Jun (32-34), we examined whether c-Jun was contained in the TH-CRE complex.…”

Section: Identification Of Atf-2 As a Transcription Factor Binding Tomentioning

confidence: 94%

“…CREB is activated by phosphorylation on Ser 133 (11,12). The activation of CREB by phosphorylation has been shown to mediate PKA-dependent (7,(13)(14)(15) and -independent (13,14) induction of TH transcription. Functional and physiological roles of ATF-1 and CREM for TH transcription remained unclear.…”

mentioning

confidence: 99%

Identification of ATF-2 as a Transcriptional Regulator for the Tyrosine Hydroxylase Gene

Suzuki

Yamakuni

Hagiwara

et al. 2002

Journal of Biological Chemistry

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Transcriptional regulation of catecholamine-synthesizing genes is important for the determination of neurotransmitters during brain development. We found that three catecholamine-synthesizing genes were transcriptionally up-regulated in cloned PC12D cells overexpressing V-1, a protein that is highly expressed during postnatal brain development (1). To reveal the molecular mechanism to regulate the expression of tyrosine hydroxylase (TH), which is the rate-limiting enzyme for catecholamine biosynthesis, we analyzed the transcription factors responsible for TH induction in the V-1 clonal cells. First, by using reporter constructs, we found that the transcription mediated by cAMP-responsive element (CRE) was selectively enhanced in the V-1 cells, and TH promoter activity was totally dependent on the CRE in the promoter region of the TH gene. Next, immunoblot analyses and a transactivation assay using a GAL4 reporter system revealed that ATF-2, but not cAMP-responsive element-binding protein (CREB), was highly phosphorylated and activated in the V-1 cells, while both CREB and ATF-2 were bound to the TH-CRE. Finally, the enhanced TH promoter activity was competitively attenuated by expression of a plasmid containing the ATF-2 transactivation domain. These data demonstrated that activation of ATF-2 resulted in the increased transcription of the TH gene and suggest that ATF-2 may be deeply involved in the transcriptional regulation of catecholamine-synthesizing genes during neural development.Catecholamines are synthesized from L-tyrosine by the sequential action of four enzymes: tyrosine is converted to DOPA by tyrosine hydroxylase (TH), 1 DOPA to dopamine by aromatic L-amino acid decarboxylase (AADC), dopamine to norepinephrine by dopamine ␤-hydroxylase (DBH), and norepinephrine to epinephrine by phenylethanolamine N-methyltransferase. The regulation of the gene expression of these enzymes is important for the determination of the expression of neurotransmitters during brain development as well as for brain function under physiological and pathological conditions. TH is the rate-limiting enzyme for catecholamine biosynthesis. The transcriptional regulation of the TH gene has been extensively studied, and many transcription factors were suggested to regulate TH gene expression. CREB, ATF-1, and CREM were shown to recognize the cAMP-responsive element (CRE) located at position Ϫ45/Ϫ38 in the TH promoter (2-6). CREB was reported to mediate basal and cAMP-induced TH transcription in various cultured cells including PC12 cells by the use of dominant-negative CREB protein and antisense RNA against CREB (7-10). CREB is activated by phosphorylation on Ser 133 (11,12). The activation of CREB by phosphorylation has been shown to mediate PKA-dependent (7, 13-15) and -independent (13, 14) induction of TH transcription. Functional and physiological roles of ATF-1 and CREM for TH transcription remained unclear. AP-1 transcription factors bound to the TPA-responsive element located at Ϫ205/Ϫ199 in the TH promoter, which also plays ...

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Promoter elements and second messenger pathways involved in transcriptional activation of tyrosine hydroxylase by ionomycin

Cited by 37 publications

References 43 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

Tyrosine Hydroxylase Gene Promoter Activity Is Regulated by Both Cyclic AMP-responsive Element and AP1 Sites following Calcium Influx

Identification of ATF-2 as a Transcriptional Regulator for the Tyrosine Hydroxylase Gene

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Promoter elements and second messenger pathways involved in transcriptional activation of tyrosine hydroxylase by ionomycin

Cited by 37 publications

References 43 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

Tyrosine Hydroxylase Gene Promoter Activity Is Regulated by Both Cyclic AMP-responsive Element and AP1 Sites following Calcium Influx

Identification of ATF-2 as a Transcriptional Regulator for the Tyrosine Hydroxylase Gene

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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