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

Bobrovskaya, Larisa and Damanhuri, Hanafi A. and Ong, Lin Kooi ORCID: https://orcid.org/0000-0001-8664-0540 and Schneider, Jennifer J. and Dickson, Phillip W. and Dunkley, Peter R. and Goodchild, Ann K. (2010) Signal transduction pathways and tyrosine hydroxylase regulation in the adrenal medulla following glucoprivation: An in vivo analysis. Neurochemistry International, 57 (2). pp. 162-167. ISSN 0197-0186


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.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Files associated with this item cannot be displayed due to copyright restrictions.
Faculty/School / Institute/Centre: No Faculty
Faculty/School / Institute/Centre: No Faculty
Date Deposited: 23 May 2022 05:26
Last Modified: 23 May 2022 05:26
Uncontrolled Keywords: Adrenal medulla; Glucoprivation; Tyrosine hydroxylase
Fields of Research (2020): 32 BIOMEDICAL AND CLINICAL SCIENCES > 3209 Neurosciences > 320903 Central nervous system
32 BIOMEDICAL AND CLINICAL SCIENCES > 3205 Medical biochemistry and metabolomics > 320506 Medical biochemistry - proteins and peptides (incl. medical proteomics)
32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320208 Endocrinology
Socio-Economic Objectives (2020): 20 HEALTH > 2001 Clinical health > 200101 Diagnosis of human diseases and conditions
20 HEALTH > 2001 Clinical health > 200199 Clinical health not elsewhere classified
20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions
Identification Number or DOI: https://doi.org/10.1016/j.neuint.2010.05.009
URI: http://eprints.usq.edu.au/id/eprint/48283

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