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■ 演 題： Central and peripheral glucoprivation;
how does tyrosine hydroxylase fit in the response?
■ 演 者： Mohd Hanafi Ahmad Damanhuri, Lecturer
(Department of Biochemistry, Faculty of Medicine,
National University of Malaysia (UKM))
■ 日 時： 平成２６年３月２５日（火）１６：００〜
■ 場 所： 基礎研究棟２階 教職員ロビー
＜講演要旨＞
Hypoglycaemia evokes distinct counter regulatory mechanisms aimed at
restoration of normal plasma glucose levels; for example, activation of the
sympathoadrenal pathway evokes the release of catecholamines, primarily
adrenaline, which stimulates glycogenolysis. The glucoprivic stimulus,
2-deoxy-d-glucose (2DG) also elicits these counter regulatory mechanisms not
only in the periphery but also in the central nervous system. Here we explored
the intracellular signalling pathways activated, in the adrenal medulla and in
specific brain regions, that are evoked by 2DG. Additionally we also explored
the expression of c-Fos in specific brain regions activated by glucoprivation.
Conscious rats were subjected to glucoprivation or vehicle for 30, 60 or 120 min and changes in the phosphorylation of serine residues 19, 31 and 40 in the
biosynthetic enzyme, tyrosine hydroxylase (TH), the activity of TH or, the
expression of c-Fos were determined, in adrenal medulla and up to ten brain
regions, simultaneously that contain catecholaminergic cell bodies and/or
terminals: A1, A2, caudal C1, rostral C1, A6, A8/9, A10, nucleus accumbens,
dorsal striatum and medial prefrontal cortex. Our results show that 2DG evoked
increases in plasma adrenaline and glucose at 20 min. In the adrenal medulla,
we found 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 stimulated.
We demonstrated that phosphorylation of Ser40TH peaked after 20 min
whereas phosphorylation of Ser31TH was still increasing at 60 min. Serine 19
was never phosphorylated. TH phosphorylation also occurred on newly
synthesized protein 24 h after 2DG. In the brain, glucoprivation evoked
phosphorylation changes in A1, caudal C1, rostral C1 and nucleus accumbens
where few changes were evident at 60 min. Specific patterns of serine residue
phosphorylation were detected, dependent upon the brain region, suggesting
activation of distinct signaling cascades. As conclusion, 2DG increases
secretion of adrenaline and glucose into the plasma, and in the adrenal medulla 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 synthesis of adrenaline.
Whilst changes in phosphorylation of TH serine residues in specific brain
regions provide a highly sensitive measure of activity, cellular signalling and catecholamine utilization in catecholaminergic brain regions, in the short term,in response to glucoprivation.
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