Signal transduction pathways and tyrosine hydroxylase regulation in the adrenal medulla following glucoprivation: An in vivo analysis

Larisa Bobrovskaya, Mohd Hanafi Ahmad Damanhuri, Lin Kooi Ong, Jennifer J. Schneider, Phillip W. Dickson, Peter R. Dunkley, Ann K. Goodchild

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The regulation of tyrosine hydroxylase (TH, the rate limiting enzyme involved in catecholamine synthesis) is critical for the acute and sustained release of catecholamines from adrenal medullary chromaffin cells, however the mechanisms involved have only ever been investigated under in vitro/. in situ conditions. Here we explored the effects on, TH phosphorylation and synthesis, and upstream signalling pathways, in the adrenal medulla evoked by the glucoprivic stimulus, 2-deoxy-d-glucose (2DG) administered intraperitoneally to conscious rats. Our results show that 2DG evoked expected increases in plasma adrenaline and glucose at 20 and 60. min. We demonstrated that protein kinase A (PKA) and cyclin dependent kinases (CDK) were activated 20. min following 2DG, whereas mitogen activated protein kinase (MAPK) was activated later and PKC was not significantly activated. We demonstrated that phosphorylation of Ser40TH peaked after 20. min whereas phosphorylation of Ser31TH was still increasing at 60. min. Serine 19 was not phosphorylated in this time frame. TH phosphorylation also occurred on newly synthesized protein 24. h after 2DG. Thus 2DG increases secretion of adrenaline into the plasma and the consequent rise in glucose levels. In the adrenal medulla 2DG activates PKA, CDK and MAPK, and evokes phosphorylation of Ser40 and Ser31 in the short term and induces TH synthesis in the longer term all of which most likely contribute to increased capacity for the synthesis of adrenaline.

Original languageEnglish
Pages (from-to)162-167
Number of pages6
JournalNeurochemistry International
Volume57
Issue number2
DOIs
Publication statusPublished - Sep 2010
Externally publishedYes

Fingerprint

Adrenal Medulla
Tyrosine 3-Monooxygenase
Signal Transduction
Glucose
Phosphorylation
Epinephrine
Cyclin-Dependent Kinases
Cyclic AMP-Dependent Protein Kinases
Mitogen-Activated Protein Kinases
Catecholamines
Chromaffin Cells
Serine
Enzymes

Keywords

  • Adrenal medulla
  • Glucoprivation
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Medicine(all)

Cite this

Signal transduction pathways and tyrosine hydroxylase regulation in the adrenal medulla following glucoprivation : An in vivo analysis. / Bobrovskaya, Larisa; Ahmad Damanhuri, Mohd Hanafi; Ong, Lin Kooi; Schneider, Jennifer J.; Dickson, Phillip W.; Dunkley, Peter R.; Goodchild, Ann K.

In: Neurochemistry International, Vol. 57, No. 2, 09.2010, p. 162-167.

Research output: Contribution to journalArticle

Bobrovskaya, Larisa ; Ahmad Damanhuri, Mohd Hanafi ; Ong, Lin Kooi ; Schneider, Jennifer J. ; Dickson, Phillip W. ; Dunkley, Peter R. ; Goodchild, Ann K. / Signal transduction pathways and tyrosine hydroxylase regulation in the adrenal medulla following glucoprivation : An in vivo analysis. In: Neurochemistry International. 2010 ; Vol. 57, No. 2. pp. 162-167.
@article{ea7e5d1a0d534051b6f44d10b6ac687f,
title = "Signal transduction pathways and tyrosine hydroxylase regulation in the adrenal medulla following glucoprivation: An in vivo analysis",
abstract = "The regulation of tyrosine hydroxylase (TH, the rate limiting enzyme involved in catecholamine synthesis) is critical for the acute and sustained release of catecholamines from adrenal medullary chromaffin cells, however the mechanisms involved have only ever been investigated under in vitro/. in situ conditions. Here we explored the effects on, TH phosphorylation and synthesis, and upstream signalling pathways, in the adrenal medulla evoked by the glucoprivic stimulus, 2-deoxy-d-glucose (2DG) administered intraperitoneally to conscious rats. Our results show that 2DG evoked expected increases in plasma adrenaline and glucose at 20 and 60. min. We demonstrated that protein kinase A (PKA) and cyclin dependent kinases (CDK) were activated 20. min following 2DG, whereas mitogen activated protein kinase (MAPK) was activated later and PKC was not significantly activated. We demonstrated that phosphorylation of Ser40TH peaked after 20. min whereas phosphorylation of Ser31TH was still increasing at 60. min. Serine 19 was not phosphorylated in this time frame. TH phosphorylation also occurred on newly synthesized protein 24. h after 2DG. Thus 2DG increases secretion of adrenaline into the plasma and the consequent rise in glucose levels. In the adrenal medulla 2DG activates PKA, CDK and MAPK, and evokes phosphorylation of Ser40 and Ser31 in the short term and induces TH synthesis in the longer term all of which most likely contribute to increased capacity for the synthesis of adrenaline.",
keywords = "Adrenal medulla, Glucoprivation, Tyrosine hydroxylase",
author = "Larisa Bobrovskaya and {Ahmad Damanhuri}, {Mohd Hanafi} and Ong, {Lin Kooi} and Schneider, {Jennifer J.} and Dickson, {Phillip W.} and Dunkley, {Peter R.} and Goodchild, {Ann K.}",
year = "2010",
month = "9",
doi = "10.1016/j.neuint.2010.05.009",
language = "English",
volume = "57",
pages = "162--167",
journal = "Neurochemistry International",
issn = "0197-0186",
publisher = "Elsevier Limited",
number = "2",

}

TY - JOUR

T1 - Signal transduction pathways and tyrosine hydroxylase regulation in the adrenal medulla following glucoprivation

T2 - An in vivo analysis

AU - Bobrovskaya, Larisa

AU - Ahmad Damanhuri, Mohd Hanafi

AU - Ong, Lin Kooi

AU - Schneider, Jennifer J.

AU - Dickson, Phillip W.

AU - Dunkley, Peter R.

AU - Goodchild, Ann K.

PY - 2010/9

Y1 - 2010/9

N2 - The regulation of tyrosine hydroxylase (TH, the rate limiting enzyme involved in catecholamine synthesis) is critical for the acute and sustained release of catecholamines from adrenal medullary chromaffin cells, however the mechanisms involved have only ever been investigated under in vitro/. in situ conditions. Here we explored the effects on, TH phosphorylation and synthesis, and upstream signalling pathways, in the adrenal medulla evoked by the glucoprivic stimulus, 2-deoxy-d-glucose (2DG) administered intraperitoneally to conscious rats. Our results show that 2DG evoked expected increases in plasma adrenaline and glucose at 20 and 60. min. We demonstrated that protein kinase A (PKA) and cyclin dependent kinases (CDK) were activated 20. min following 2DG, whereas mitogen activated protein kinase (MAPK) was activated later and PKC was not significantly activated. We demonstrated that phosphorylation of Ser40TH peaked after 20. min whereas phosphorylation of Ser31TH was still increasing at 60. min. Serine 19 was not phosphorylated in this time frame. TH phosphorylation also occurred on newly synthesized protein 24. h after 2DG. Thus 2DG increases secretion of adrenaline into the plasma and the consequent rise in glucose levels. In the adrenal medulla 2DG activates PKA, CDK and MAPK, and evokes phosphorylation of Ser40 and Ser31 in the short term and induces TH synthesis in the longer term all of which most likely contribute to increased capacity for the synthesis of adrenaline.

AB - The regulation of tyrosine hydroxylase (TH, the rate limiting enzyme involved in catecholamine synthesis) is critical for the acute and sustained release of catecholamines from adrenal medullary chromaffin cells, however the mechanisms involved have only ever been investigated under in vitro/. in situ conditions. Here we explored the effects on, TH phosphorylation and synthesis, and upstream signalling pathways, in the adrenal medulla evoked by the glucoprivic stimulus, 2-deoxy-d-glucose (2DG) administered intraperitoneally to conscious rats. Our results show that 2DG evoked expected increases in plasma adrenaline and glucose at 20 and 60. min. We demonstrated that protein kinase A (PKA) and cyclin dependent kinases (CDK) were activated 20. min following 2DG, whereas mitogen activated protein kinase (MAPK) was activated later and PKC was not significantly activated. We demonstrated that phosphorylation of Ser40TH peaked after 20. min whereas phosphorylation of Ser31TH was still increasing at 60. min. Serine 19 was not phosphorylated in this time frame. TH phosphorylation also occurred on newly synthesized protein 24. h after 2DG. Thus 2DG increases secretion of adrenaline into the plasma and the consequent rise in glucose levels. In the adrenal medulla 2DG activates PKA, CDK and MAPK, and evokes phosphorylation of Ser40 and Ser31 in the short term and induces TH synthesis in the longer term all of which most likely contribute to increased capacity for the synthesis of adrenaline.

KW - Adrenal medulla

KW - Glucoprivation

KW - Tyrosine hydroxylase

UR - http://www.scopus.com/inward/record.url?scp=77953912956&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953912956&partnerID=8YFLogxK

U2 - 10.1016/j.neuint.2010.05.009

DO - 10.1016/j.neuint.2010.05.009

M3 - Article

C2 - 20493917

AN - SCOPUS:77953912956

VL - 57

SP - 162

EP - 167

JO - Neurochemistry International

JF - Neurochemistry International

SN - 0197-0186

IS - 2

ER -