Induction of tyrosine hydroxylase gene expression by a nonneuronal nonpituitary-mediated mechanism in immobilization stress.

Nankova, Bistra B.; Květňanský, Richard; McMahon, Anne; Viskupic, E; Hiremagalur, Bhargava; Frankle, W. Gordon; Fukuhara, Kazunobu; Kopin, Irwin J.; Sabban, Esther L.

doi:10.1073/pnas.91.13.5937

Cited by 110 publications

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“…Thus, elevation of PNMT is largely dependent on hormonal regulation at its glucocorticoid regulatory responseelement (Ross et al, 1990), and hypophysectomy prevents the induction of PNMT by stress, whereas TH, DBH, and NPY responses are affected only slightly (Nankova et al, 1994;Viskupic et al, 1994;Sabban et al, 1996). Transsynaptic nicotinic nerve stimulation is essential for the induction of adrenomedullary NPY , whereas immobilization stress was found to enable elevation of TH and c-Fos mRNAs by a nonneuronal, nonpituitarymediated pathway (Nankova et al, 1994;Sabban et al, 1995).In addition to the stress effects in the adrenal medulla, these genes are also elevated by stress in both the noradrenergic neurons of sympathetic ganglia and the locus ceruleus, the major noradrenergic cell bodies in the brainstem (Angulo et al, 1991;Mamalaki et a!., 1992;. However, there appear to be tissue-specific differences.…”

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“…c-fos is a 62-kDa nuclear protooncogene that forms heterodimers with members of the Jun family; these complexes bind to AP-1 sites (core consensus of TGAG/CTCA) to regulate transcription (Angel and Karin, 1991). Immobilization and cold stress-elicited induction of cFos and increased binding to the AP-1-like site (TGA-TTCAG) in the TH promoter have been correlated with elevation in adrenal TH transcription (Miner et al, 1992;Nankova et a!., 1994). However, direct evidence regarding the role of c-Fos in mediating this induction or any stress-elicited changes in gene expression has been lacking.…”

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c‐Fos Deficiency Inhibits Induction of mRNA for Some, but Not All, Neurotransmitter Biosynthetic Enzymes by Immobilization Stress

Serova

Sáez

Spiegelman

et al. 1998

Journal of Neurochemistry

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Recent studies indicated that c-Fos protein may be mediating stress-elicited transcriptional activation of genes involved in neurotransmitter biosynthesis. However, direct evidence for c-Fos mediating these changes in gene expression has been lacking. Mice with disrupted c-fos gene(+I-or -I-genotypes) were used to examine the effect of immobilization stress on a group of stress-responsive genes. In male adrenals, c-Fos was found not essential for stress-elicited activation of expression of tyrosine hydroxylase, dopamine /3-hydroxylase (DBH), phenylethanolamine N-methyltransferase, or neuropeptide Y. In females, immobilization failed to induce adrenal DBH in the c-Fos-deficient mice. In brainstem, c-Fos was indispensable for elevation of DBH mRNA in both genders. The gene, gender, and tissue specificity in the requirement for c-Fos points to diversity in adaptation mechanisms to stress. KeyWords: c-FosImmobilization stress-Gene expression -Tyrosine hydroxylase-Dopamine~3-hydroxyIase-Phenylethanolamine N-methyltransferase-Neuropeptide Y-Gender. J. Neurochem. 70, 1935Neurochem. 70, -1940Neurochem. 70, (1998.Prolonged stress is well recognized as a major contributor to increased incidence of cardiovascular disorders, such as hypertension and myocardial infarction; mental diseases, such as panic, anxiety, eating, and depressive disorders; and gastrointestinal problems, such as ulcers. Stress also increases the susceptibility to infection, autoimmune disorders, and cancer (Seyle, 1975;Ramsey, 1982). The main components of the stress system are the hypothalamic corticotropin-releasing hormone and the locus ceruleus norepinephrine/autonomic systems and their peripheral effectors, the pituitary-adrenal axis and the limbs of the autonomic system that enable the organism to overcome immediate threats to its homeostasis (for review, see Chrousos and Gold, 1992). Many of the detrimental effects of prolonged stress are likely associated with alterations in gene expression.Circulating catecholamine levels soar with stress and are accompanied by increases in several neuropeptides, such as neuropeptide Y (NPY), which can p0-tentiate adrenergic vasoconstriction (Zukowska-Grojec and Wahlestedt, 1993;Goldstein, 1995). Stress leads to marked and prolonged elevations in the expression of several gene products in the sympathoadrenal system. In the adrenal medulla, the catecholamine biosynthetic enzymes, tyrosine hydroxylase (TH), dopamine~3-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT), several neuropeptide precursors, such as NPY and preproenkephalin, as well as c-Fos, are transcriptionally induced by stress (Sabban et a!., 1995. Although their expression is elevated by immobilization stress, different mechanisms appear to be responsible for their induction. Thus, elevation of PNMT is largely dependent on hormonal regulation at its glucocorticoid regulatory responseelement (Ross et al., 1990), and hypophysectomy prevents the induction of PNMT by stress, whereas TH, DBH, and NPY responses are affect...

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confidence: 99%

mentioning

confidence: 99%

c‐Fos Deficiency Inhibits Induction of mRNA for Some, but Not All, Neurotransmitter Biosynthetic Enzymes by Immobilization Stress

Serova

Sáez

Spiegelman

et al. 1998

Journal of Neurochemistry

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“…Some researchers (Nankova et al 1994;Kubovcakova et al 2004) have measured mRNA expression levels of catecholamine biosynthetic enzymes in the sympathetic ganglia after various kinds of stress and concluded that repeated and longer observation periods were required to detect an increase in the levels of transcripts in the sympathetic ganglia than in the adrenal glands. In those experiments, the shortest observation intervals were 2 h, which is much longer than those of the present study.…”

Section: Expression Levels Of Target Mrnas In the Anterocervical Gangliamentioning

confidence: 99%

“…On the other hand, measurement of sympathoadrenal activity based on expression levels of mRNAs for catecholamine biosynthetic enzymes has been performed in the field of molecular biology (Nankova et al 1994;Nankova et al 1996;Brooks et al 1997;Levenson and Moore 1998;Rusnák et al 1998;Bornstein et al 1999;Lai et al 2000;Sabban and Kvetnanský 2001;Gallara et al 2004;Kubovcakova et al 2004;Klimes et al 2005;Lai et al 2005;Herradón et al 2006). However, earlier animal studies on some stresses such as immobilization, cold exposure, forced exercise, and insulininduced hypoglycemia (Brooks et al 1997;Lai et al 2000;Sabban and Kvetnanský 2001;Gallara et al 2004;Klimes et al 2005;Lai et al 2005), did not cover all forms of stresses encountered in forensic practice.…”

confidence: 99%

“…However, earlier animal studies on some stresses such as immobilization, cold exposure, forced exercise, and insulininduced hypoglycemia (Brooks et al 1997;Lai et al 2000;Sabban and Kvetnanský 2001;Gallara et al 2004;Klimes et al 2005;Lai et al 2005), did not cover all forms of stresses encountered in forensic practice. Moreover, most of the methods in the analysis including Southern blotting and semi-quantitative reverse trancrptional polymerase chain reaction (RT-PCR) (Nankova et al 1994;Nankova et al 1996;Brooks et al 1997;Lai et al 2000;Kubovcakova et al 2004;Gallara et al 2004;Lai et al 2005), require some experience to produce reliably reproducible results. In recent years, real-time quantitative PCR (RQ-PCR) has been established as a simplified and reproducible method for the quantification of mRNA expression, and some investigators have used this technique for assaying levels of catecholamine mRNA expression (Bornstein et al 1999;Kvetnansky et al 2004;Herradón et al 2006).…”

confidence: 99%

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Expression Levels of mRNAs for Catecholamine Biosynthetic Enzymes as Markers of Acute Response to Contusion Stress during the Early Postmortem Period

Takahashi

2008

Tohoku J. Exp. Med.

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Various stresses can be followed by sudden unexpected deaths, and autopsies sometimes fail to identify pathological findings that determine the cause of death. Pathologists occasionally explain such deaths as being due to overstimulation of sympathoadrenal systems, but postmortem assessment of antemortem sympathoadrenal activity has not been established. An animal model of weight injuries was used to quantify sympathoadrenal response to contusion stress, which is common in forensic fields. A weight was dropped from a given height onto the right dorsal limb of each anesthetized rat, with a control group and three stress groups (n = 4, each): 1000 g-80 cm, 1000 g-40 cm, and 500 g-40 cm. To explore the postmortem changes, we also included ten groups comprised of control and 1000 g-80 cm groups, whose tissues were harvested during 12 hours after euthanasia. Real-time quantitative polymerase-chain reaction was performed to quantify relative expression levels of mRNAs for catecholamine biosynthetic enzymes in the adrenals and the anterocervical ganglia: tyrosine hydroxylase (TH), dopamine betahydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT). The expression levels of all target mRNAs in the adrenals increased with the intensity of impact (TH, p < 0.0005; DBH and PNMT, p < 0.005), and particularly, TH mRNA level exhibited near-stepwise elevation ( p < 0.05). In contrast, no significant differences were detected in the anterocervical ganglia. Moreover, these mRNA levels in the adrenals decreased with increasing postmortem interval length. Thus, TH mRNA level may be a good marker of sympathoadrenal response to contusion stress during the early postmortem period. forensic medicine; sudden unexpected death; sympathoadrenal response to contusion stress; catecholamine; real-time quantitative polymerase chain reaction.Tohoku

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AP-1 mediates trans-synaptic induction of tyrosine hydroxylase gene expression in adrenal medulla but not in superior cervical ganglia

1997

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Reserpine treatment leads to a rapid trans-synaptic increase of the tyrosine hydroxylase (TH) gene transcription rate and mRNA levels in catecholaminergic tissues including the adrenal medulla (AM) and the superior cervical ganglia (SCG). In the AM, the formation of a specific protein complex with the TPA-responsive element located in the proximal region of the TH gene was enhanced between 30 min and 8 hr following the injection. This complex appears to contain a member of the Fos family and an antigenically related Jun protein. Moreover, the prolonged and enhanced expression of the c-Fos protein in the AM and its phosphorylation are likely to contribute to the increased TH transcription following reserpine treatment. Most strikingly, in the SCG, the trans-synaptic induction of TH transcription is transduced by totally different mechanisms, since no AP-1 complex and only minute amounts of c-Fos immunoreactivity were detected. Our study provides the first demonstration that, following the same stimulus, the induced expression of a single gene is mediated by different cis- and trans-acting factors in two distinct tissues sharing the same embryonic origin.

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Induction of tyrosine hydroxylase gene expression by a nonneuronal nonpituitary-mediated mechanism in immobilization stress.

Abstract: Stress stmulates the sympathoadrenal sys-

Cited by 110 publications

References 36 publications

c‐Fos Deficiency Inhibits Induction of mRNA for Some, but Not All, Neurotransmitter Biosynthetic Enzymes by Immobilization Stress

c‐Fos Deficiency Inhibits Induction of mRNA for Some, but Not All, Neurotransmitter Biosynthetic Enzymes by Immobilization Stress

Expression Levels of mRNAs for Catecholamine Biosynthetic Enzymes as Markers of Acute Response to Contusion Stress during the Early Postmortem Period

AP-1 mediates trans-synaptic induction of tyrosine hydroxylase gene expression in adrenal medulla but not in superior cervical ganglia

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