Transcriptional and post-transcriptional regulation of tyrosine hydroxylase gene by protein kinase C.

Vyas, Sheela; Biguet, Nicole Faucon; Mallet, Jacques

doi:10.1002/j.1460-2075.1990.tb07583.x

Cited by 102 publications

(84 citation statements)

References 52 publications

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“…This difference results from an absolute enrichment for PCBP 1 , as similar increases were measured using total cellular lysates, and immunocytochemistry did not show any intracellular translocation in the PCBP 1 content. 2 This difference in the hypoxic inducibility of the two isoforms supports the observation that although PCBP 1 and PCBP 2 have high degrees of sequence homology, they show some specific functional differences, such as efficiency of interacting with AUF1 protein (19) or efficiency to regulate poliovirus translation (12).…”

supporting

confidence: 68%

“…Recently, there has been growing evidence that TH mRNA is also regulated at the level of mRNA stability. TH mRNA is a stable message with a half-life that varies from 9 to 16 h in various subclones of PC12 cells (1)(2)(3). It is enhanced during differentiation of neuroblastoma cells (1) and during stimulation of the protein kinase C pathway in PC12 cells (2).…”

mentioning

confidence: 99%

“…TH mRNA is a stable message with a half-life that varies from 9 to 16 h in various subclones of PC12 cells (1)(2)(3). It is enhanced during differentiation of neuroblastoma cells (1) and during stimulation of the protein kinase C pathway in PC12 cells (2). In contrast, the stability of TH mRNA does not change in PC12 cells during stimulation of TH mRNA expression by dexamethasone or forskolin (3).…”

mentioning

confidence: 99%

“…So far we did not find any evidence for the presence of AUF protein in the HIPBS-associated complex. 2 The protein-binding motifs within the TH and ␣ 2 -globin mRNAs show some potentially important differences. Whereas the essential PCBP-binding motifs are very similar in the two mRNAs (11), in the case of TH mRNA the binding motif is located in the middle of a long pyrimidine-rich sequence, and in the case of ␣ 2 -globin mRNA the short binding motifs are separated by purine-rich sequences.…”

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confidence: 99%

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Regulation of Tyrosine Hydroxylase mRNA Stability by Protein-binding, Pyrimidine-rich Sequence in the 3′-Untranslated Region

Paulding¹,

Czyzyk-Krzeska

1999

Journal of Biological Chemistry

128

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The stability of mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, is regulated by oxygen tension in the pheochromocytomaderived PC12 cell line. We previously identified a pyrimidine-rich 27-base-long protein-binding sequence in the 3-untranslated region of TH mRNA that is associated with hypoxia-inducible formation of a ribonucleoprotein complex (hypoxia-inducible protein-binding site (HIPBS)). In this study, we show that HIPBS is an mRNA stabilizing element necessary for both constitutive and hypoxia-regulated stability of TH mRNA. The mutations within this sequence that abolish protein binding markedly decrease constitutive TH mRNA stability and ablate its hypoxic regulation. A short fragment of TH mRNA that contains the wild-type HIPBS confers the increased mRNA stability to the reporter chloramphenicol acetyltransferase mRNA. However, it is not sufficient to confer hypoxic regulation. The HIPBS element binds two isoforms of a 40-kDa poly(C)-binding protein (PCBP). Hypoxia induces expression of the isoform 1, PCBP 1 , but not the isoform 2, PCBP 2 , in PC12 cells.Tyrosine hydroxylase (TH), 1 the rate-limiting enzyme in the biosynthesis of catecholamines, is expressed in specific populations of neurons in the central and peripheral nervous systems, in the neuroendocrine cells of the adrenal medulla and carotid body, and in cultured cell lines such as the pheochromocytomaderived PC12 cell line. Regulation of TH gene expression at the level of gene transcription is well documented. Recently, there has been growing evidence that TH mRNA is also regulated at the level of mRNA stability. TH mRNA is a stable message with a half-life that varies from 9 to 16 h in various subclones of PC12 cells (1-3). It is enhanced during differentiation of neuroblastoma cells (1) and during stimulation of the protein kinase C pathway in PC12 cells (2). In contrast, the stability of TH mRNA does not change in PC12 cells during stimulation of TH mRNA expression by dexamethasone or forskolin (3). A recent study demonstrated substantial differences in basal TH mRNA turnover rates between different neuronal populations from as short a time as 6 -7 h, in the dopaminergic neurons of the arcuate nucleus, to as long as 11-23 h, in the dopaminergic midhypothalamic neurons (4). In addition, TH mRNA is destabilized in the dopaminergic cells of the arcuate nucleus in a manner that corresponds to the rhythmic output displayed by these neurons (4).Our laboratory demonstrated that hypoxia augments the stability of TH mRNA in PC12 cells (5). We identified a 27-base-long pyrimidine-rich sequence within the TH mRNA 3Ј-untranslated region (UTR) (1552-1578 bases of TH mRNA) that binds protein factors in a hypoxia-inducible manner (hypoxia-inducible protein-binding sequence (HIPBS)) in PC12 cells (6, 7), catecholaminergic cells of the superior cervical ganglia, and the dopaminergic cells of the carotid body (8). Mutational analysis revealed that the optimal protein-binding site is represented by the motif (U/C)(C/...

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confidence: 68%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Regulation of Tyrosine Hydroxylase mRNA Stability by Protein-binding, Pyrimidine-rich Sequence in the 3′-Untranslated Region

Paulding¹,

Czyzyk-Krzeska

1999

Journal of Biological Chemistry

128

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“…For instance, chronic VPA treatment has been shown to decrease levels of PKC alpha and epsilon (Chen et al 1994). This has been suggested to be a result of chronic PKC activation (Manji and Lenox 1994), and activation of PKC by administration of phorbol ester activates TH gene transcription (Vyas et al 1990). Chronic VPA treatment has also been shown to decrease levels of myristoylated alanine-rich C kinase substrate (MARCKS) (Lenox et al 1996), providing further evidence of an interaction of VPA with PKC.…”

Section: Discussionmentioning

confidence: 99%

Changes in Tyrosine Hydroxylase mRNA Expression in the Rat Locus Coeruleus Following Acute or Chronic Treatment with Valproic Acid

Sands

Guerra

Morilak

2000

Neuropsychopharmacology

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Valproate has proven effective in treating bipolar disorder. Though some biochemical effects of valproate are rapid, mood-stabilizing effects can take weeks, suggesting that regulatory changes in gene expression in brain neurotransmitter systems may be involved. Given a presumed role for norepinephrine (NE) in bipolar disorder, as well as the actions of mood-stabilizing drugs, we examined changes in mRNA expression for tyrosine hydroxylase (TH), the NE transporter (NET) andIt has long been hypothesized that dysregulation of central norepinephrine (NE) neuronal systems might be involved in the expression if not the development of major affective disorders, including depression and mania (Schatzberg and Schildkraut 1995;Schildkraut 1965). The noradrenergic neurons of the locus coeruleus (LC), situated in the dorsal pons, project widely throughout the central nervous system, representing the source of noradrenergic terminals innervating many forebrain and limbic regions such as the amygdala, hippocampus, hypothalamus and neocortex (Moore and Bloom 1979). As such, these neurons are ideally poised to exert global modulatory or state-related changes in brain activity. Central NE, and the LC in particular, is hypothesized to play an important role in attention, arousal and behavioral activation (Aston-Jones et al. 1991;Charney et al. 1990;Foote et al. 1983;Puumala et al. 1997;Siegel and Rogawski 1988), all of which may be severely disrupted in mood disorders, especially those involving a manic component such as bipolar affective disorder. Thus, the noradrenergic neurons of the LC may represent potential targets for mood stabilizing drug treat- Effective therapeutic agents have been developed for the treatment of bipolar disorder. Lithium has been the primary treatment for bipolar disorder, although its side effects are many and often severe, and its mechanism of action is still relatively unknown (Bowden et al. 1994). Recently, certain classes of antiepileptic agents, including valproic acid (VPA), have proven to be as effective as lithium in the treatment of mania and bipolar disorder, and possess a more benign adverse effect profile and a broader therapeutic margin of safety (Bowden et al. 1994;Loscher 1993). The mechanism of action of VPA for the treatment of affective disorders is largely unknown. By contrast, the mechanisms by which it acts as an antiepileptic have been more extensively examined. The biochemical effects of VPA occur rapidly, and include the inhibition of GABA transaminase (and thus inhibition of GABA catabolism) and a decrease in sodium channel activity (Van den Berg et al. 1993). Similarly, the antiepileptic effects of VPA are observed quickly, whereas the antimanic effects of VPA require a much longer course of treatment, as long as 2-3 weeks (Bowden et al. 1994). Because of this, the mechanisms of action underlying the antimanic action of VPA may be distinct from those underlying its antiepileptic effects. Thus, it would be informative to investigate the induction of long-term regulatory, react...

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Tyrosine Hydroxylase

Kaufman¹

1995

Advances in Enzymology - And Related Areas of Molecular Biology

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a b o r a t o r y of N e u r o c h e m i s t r y , N a t i o n a l I n s t i t u t e of M e n t a l H e a l t h , B e t h e s d a , Maryland the first step in the biosynthesis of norepinephrine and epinephrine involved the conversion of tyrosine to 3,4dihydroxyphenylalanine (dopa), followed by decarboxylation of the dopa to dopamine, which was then hydroxylated in the p position of the side chain and methylated on the amino group to form norepinephrine and epinephrine, respectively (Fig. 1). Although the evidence in favor of the pathway proposed by Blaschko continued to mount (5-8), and it is now widely accepted as the only quantitatively important one, the enzyme responsible for the ring hydroxylation SEYMOUR KAUFMAN droxylation of phenylalanine (17, 18), this product was also shown to be found during the TH-catalyzed conversion of tyrosine to dopa. (For a further discussion of this aspect of the reaction, see Section XI and Fig. 7.) Intracellular Localization and Regional DistributionAs already mentioned, TH is present in brain, adrenal medulla, and sympathetically innervated tissues. Its intracellular location in these tissues, however, has been the subject of controversy. Udenfriend and co-workers (12) reported that in guinea pig brain all of the activity, and in beef adrenal medulla, most of the activity, was particle bound. They further concluded that the hydroxylase found in the soluble fraction of adrenal medulla was originally present in particles from which it had been released by the homogenization process, a conclusion that was strengthened by the finding that about 90% of the activity was sedimentable after centrifugation for 1 h at 144,000 g. These findings appeared to support the proposal that all of the enzymes involved in catecholamine biosynthesis are localized within a catecholamine-containing granule (19).There is a growing body of evidence that contradicts the conclusion that TH is present intracellularly within a granule (20, 21). For the enzyme from both adrenal medulla and nerve tissue, it has been found that a major fraction of the activity is present in the highspeed supernatant fraction and that the distribution of hydroxylase activity is a function of the composition of the homogenization medium; homogenization in isotonic KC1 leads to more enzyme in the supernatant fraction than does homogenization in isotonic sucrose (21). At least part of the uncertainty about the intracellular localization of TH can be traced to the tendency of the enzyme from bovine adrenal medulla, and probably from other tissues as well, to aggregate and to adsorb to subcellular organelles (21).Although there is now a near consensus in favor of the view that the high molecular weight form of the enzyme in adrenal medulla is an artifact that is formed during cell disruption and that it is not in equilibrium with the native, nonaggregated form (22), that conclusion does not apply to brain where the enzyme appears to exist in two distinct forms, a soluble and a membrane-bound form. In fact, in the earliest studies...

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Transcriptional and post-transcriptional regulation of tyrosine hydroxylase gene by protein kinase C.

Cited by 102 publications

References 52 publications

Regulation of Tyrosine Hydroxylase mRNA Stability by Protein-binding, Pyrimidine-rich Sequence in the 3′-Untranslated Region

Regulation of Tyrosine Hydroxylase mRNA Stability by Protein-binding, Pyrimidine-rich Sequence in the 3′-Untranslated Region

Changes in Tyrosine Hydroxylase mRNA Expression in the Rat Locus Coeruleus Following Acute or Chronic Treatment with Valproic Acid

Tyrosine Hydroxylase

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