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Stress Triggered Changes in Expression of Genes for Neurosecretory Granules in Adrenal Medulla

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Abstract

With acute stress, the release of adrenomedullary catecholamines is important for handling the emergency situation. However, when chronic or repeated, stress alters the allostatic load and leads to a hyperadrenergic state, resulting in the development or worsening of a wide range of diseases. To help elucidate the mechanism, we examined the effects of single and repeated immobilization stress on gene expression of components of neurosecretory vesicles in the adrenal medulla. Male Sprague–Dawley rats were exposed to immobilization stress once for 2 h (1× IMO) or daily for six consecutive days (6× IMO). Compared to unstressed controls, 1× IMO elevated gene expression of vesicular monoamine transporter 2 (VMAT2). In response to 6× IMO, not only was VMAT2 mRNA still elevated, but chromogranin A (CgA) and chromogranin B (CgB) mRNAs were also increased two to three-fold above basal levels. To investigate the possible role of the hypothalamic–pituitary–adrenal axis in the induction of VMAT2, PC12 cells were treated with the synthetic glucocorticoid dexamethasone, which was found to elevate VMAT2 mRNA expression. The findings suggest that following repeated stress, elevations of various components of neurosecretory vesicles in the adrenal can facilitate more efficient utilization of the well-characterized heightened catecholamine levels.

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References

  • Bartolomucci A, Palanza P, Costoli T, Savani E, Laviola G, Parmigiani S, Sgoifo A (2003) Chronic psychosocial stress persistently alters autonomic function and physical activity in mice. Physiol Behav 80:57–67

    Article  PubMed  CAS  Google Scholar 

  • Borges R, Diaz-Vera J, Dominguez N, Arnau MR, Machado JD (2010) Chromogranins as regulators of exocytosis. J Neurochem 114:335–343

    Article  PubMed  CAS  Google Scholar 

  • Chen Y, Rao F, Wen G et al (2010) Naturally occurring genetic variants in human chromogranin A (CHGA) associated with hypertension as well as hypertensive renal disease. Cell Mol Neurobiol 30:1395–1400

    Article  PubMed  CAS  Google Scholar 

  • Cramer T, Jüttner S, Plath T, Mergler S, Seufferlein T, Wang TC, Merchant J, Höcker M (2008) Gastrin transactivates the chromogranin A gene through MEK-1/ERK- and PKC-dependent phosphorylation of Sp1 and CREB. Cell Signal 20:60–72

    Article  PubMed  CAS  Google Scholar 

  • Eisenhofer G, Rundqvist B, Friberg P (1998) Determinants of cardiac tyrosine hydroxylase activity during exercise-induced sympathetic activation in humans. Am J Physiol 274:R626–R634

    PubMed  CAS  Google Scholar 

  • Eisenhofer G, Kopin IJ, Goldstein DS (2004) Leaky catecholamine stores: undue waste or a stress response coping mechanism? Ann N Y Acad Sci 1018:224–230

    Article  PubMed  CAS  Google Scholar 

  • Erickson JD, Schafer MK, Bonner TI, Eiden LE, Weihe E (1996) Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter. Proc Natl Acad Sci USA 93:5166–5171

    Article  PubMed  CAS  Google Scholar 

  • Goldstein DS (1995) Stress, catecholamines and cardiovascular disease. Oxford University Press, Oxford

    Google Scholar 

  • Helle KB, Reed RK, Pihl KE, Serck-Hanssen G (1985) Osmotic properties of the chromogranins and relation to osmotic pressure in catecholamine storage granules. Acta Physiol Scand 123:21–33

    Article  PubMed  CAS  Google Scholar 

  • Huh YH, Jeon SH, Yoo SH (2003) Chromogranin B-induced secretory granule biogenesis: comparison with the similar role of chromogranin A. J Biol Chem 278:40581–40589

    Article  PubMed  CAS  Google Scholar 

  • Iacangelo AL, Eiden LE (1995) Chromogranin A: current status as a precursor for bioactive peptides and a granulogenic/sorting factor in the regulated secretory pathway. Regul Pept 58:65–88

    Article  PubMed  CAS  Google Scholar 

  • Kopin IJ (1964) Storage and metabolism of catecholamines: the role of monoamine oxidase. Pharmacol Rev 16:179–191

    PubMed  CAS  Google Scholar 

  • Kvetnansky R, Mikulaj L (1970) Adrenal and urinary catecholamines in rats during adaptation to repeated immobilization stress. Endocrinology 87:738–743

    Article  PubMed  CAS  Google Scholar 

  • Kvetnansky R, Mitro A, Mikulaj L, Hocman G (1966) Bratisl Lek Listy 46:35–41

    PubMed  CAS  Google Scholar 

  • Kvetnansky R, Sabban EL, Palkovits M (2009) Catecholaminergic systems in stress: structural and molecular genetic approaches. Physiol Rev 89:535–606

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Kvetnansky R, Serova L, Sollas A, Sabban EL (2005) Increased susceptibility to transcriptional changes with novel stressor in adrenal medulla of rats exposed to prolonged cold stress. Brain Res Mol Brain Res 141:19–29

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Serova L, Kvetnansky R, Sollas A, Sabban EL (2008) Identifying the stress transcriptome in the adrenal medulla following acute and repeated immobilization. Ann N Y Acad Sci 1148:1–28

    Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408

    Article  PubMed  CAS  Google Scholar 

  • Lupien SJ, McEwen BS, Gunnar MR, Heim C (2009) Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 10:434–445

    Article  PubMed  CAS  Google Scholar 

  • Maas JW (1970) A kinetic model for the study of the disposition of circulating norepinephrine. J Pharmacol Exp Ther 174:369–378

    PubMed  CAS  Google Scholar 

  • Machado JD, Díaz-Vera J, Domínguez N, Alvarez CM, Pardo MR, Borges R (2010) Chromogranins A and B as regulators of vesicle cargo and exocytosis. Cell Mol Neurobiol 30:1181–1187

    Article  PubMed  CAS  Google Scholar 

  • Mahapatra NR, Mahata M, Ghosh S, Gayen JR, O’Connor DT, Mahata SK (2006) Molecular basis of neuroendocrine cell type-specific expression of the chromogranin B gene: crucial role of the transcription factors CREB, AP-2, Egr-1 and Sp1. J Neurochem 99:119–133

    Article  PubMed  CAS  Google Scholar 

  • Mahata SK, O’Connor DT, Mahata M, Yoo SH, Taupenot L, Wu H, Gill BM, Parmer RJ (1997) Novel autocrine feedback control of catecholamine release. A discrete chromogranin a fragment is a noncompetitive nicotinic cholinergic antagonist. J Clin Invest 100:1623–1633

    Article  PubMed  CAS  Google Scholar 

  • Nankova B, Kvetnansky R, McMahon A, Viskupic E, Hiremagalur B, Frankle G, Fukuhara K, Kopin IJ, Sabban EL (1994) Induction of tyrosine hydroxylase gene expression by a nonneuronal nonpituitary-mediated mechanism in immobilization stress. Proc Natl Acad Sci USA 91:5937–5941

    Article  PubMed  CAS  Google Scholar 

  • Natori S, Huttner WB (1996) Chromogranin B (secretogranin I) promotes sorting to the regulated secretory pathway of processing intermediates derived from a peptide hormone precursor. Proc Natl Acad Sci USA 93:4431–4436

    Article  PubMed  CAS  Google Scholar 

  • Papanikolaou NA, Sabban EL (1999) Sp1/Egr1 motif: a new candidate in the regulation of rat tyrosine hydroxylase gene transcription by immobilization stress. J Neurochem 73:433–436

    Article  PubMed  CAS  Google Scholar 

  • Peter D, Jimenez J, Liu Y, Kim J, Edwards RH (1994) The chromaffin granule and synaptic vesicle amine transporters differ in substrate recognition and sensitivity to inhibitors. J Biol Chem 269:7231–7237

    PubMed  CAS  Google Scholar 

  • Pothos EN, Larsen KE, Krantz DE, Liu Y, Haycock JW, Setlik W, Gershon MD, Edwards RH, Sulzer D (2000) Synaptic vesicle transporter expression regulates vesicle phenotype and quantal size. J Neurosci 20:7297–7306

    PubMed  CAS  Google Scholar 

  • Sabban EL, Kvetnansky R (2001) Stress-triggered activation of gene expression in catecholaminergic systems: dynamics of transcriptional events. Trends Neurosci 24:91–98

    Article  PubMed  CAS  Google Scholar 

  • Sabban EL, Liu X, Serova L, Gueorguiev V, Kvetnansky R (2006) Stress triggered changes in gene expression in adrenal medulla: transcriptional responses to acute and chronic stress. Cell Mol Neurobiol 26:845–854

    Article  PubMed  CAS  Google Scholar 

  • Schoneveld OJ, Gaemers IC, Lamers WH (2004) Mechanisms of glucocorticoid signalling. Biochim Biophys Acta 1680:114–128

    PubMed  CAS  Google Scholar 

  • Serova L, Nankova B, Rivkin M, Kvetnansky R, Sabban EL (1997) Glucocorticoids elevate GTP cyclohydrolase I mRNA levels in vivo and in PC12 cells. Brain Res Mol Brain Res 48:251–258

    Article  PubMed  CAS  Google Scholar 

  • Simon JP, Bader MF, Aunis D (1988) Secretion from chromaffin cells is controlled by chromogranin A-derived peptides. Proc Natl Acad Sci USA 85:1712–1716

    Article  PubMed  CAS  Google Scholar 

  • Taupenot L, Harper KL, O’Connor DT (2003) The chromogranin-secretogranin family. N Engl J Med 348:1134–1149

    Article  PubMed  CAS  Google Scholar 

  • Tillinger A, Sollas A, Serova LI, Kvetnansky R, Sabban EL (2010) Vesicular monoamine transporters (VMATs) in adrenal chromaffin cells: stress-triggered induction of VMAT2 and expression in epinephrine synthesizing cells. Cell Mol Neurobiol 30:1459–1465

    Article  PubMed  CAS  Google Scholar 

  • Ulrich-Lai YM, Figueiredo HF, Ostrander MM, Choi DC, Engeland WC, Herman J (2006) Chronic stress induces adrenal hyperplasia and hypertrophy in a subregion-specific manner. Am J Physiol Endocrinol Metab 291(5):E965–E973

    Google Scholar 

  • Videen JS, Mezger MS, Chang YM, O’Connor DT (1992) Calcium and catecholamine interactions with adrenal chromogranins. Comparison of driving forces in binding and aggregation. J Biol Chem 267:3066–3073

    PubMed  CAS  Google Scholar 

  • Watson F, Deavall DG, Macro JA, Kiernan R, Dimaline R (1999) Transcriptional activation of vesicular monoamine transporter 2 in the pre-B cell line Ea3.123. Biochem J 337(Pt 2):193–199

    Article  PubMed  CAS  Google Scholar 

  • Westermann R, Stögbauer F, Unsicker K, Lietzke R (1988) Calcium-dependence of chromogranin A-catecholamine interaction. FEBS Lett 239:203–206

    Article  PubMed  CAS  Google Scholar 

  • Wong DL, Tank AW (2007) Stress-induced catecholaminergic function: transcriptional and post-transcriptional control. Stress 10:121–130

    Article  PubMed  CAS  Google Scholar 

  • Zhang K, Rao F, Rana BK et al (2009) Autonomic function in hypertension; role of genetic variation at the catecholamine storage vesicle protein chromogranin B. Circ Cardiovasc Genet 2:46–56

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The authors gratefully acknowledge support by grant-in-aid number 10GRNT4420001 from the American Heart Association.

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Correspondence to Esther Louise Sabban.

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Sabban, E.L., Tillinger, A., Nostramo, R. et al. Stress Triggered Changes in Expression of Genes for Neurosecretory Granules in Adrenal Medulla. Cell Mol Neurobiol 32, 795–800 (2012). https://doi.org/10.1007/s10571-011-9785-z

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  • DOI: https://doi.org/10.1007/s10571-011-9785-z

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