Disease relevance of TH

• One of these monoclonal antibodies, TH-2D8-2, can be used for immunocytochemical localization of TH in cell bodies, dendrites, and axons in catecholaminergic neurons (e.g., cells in the substantia nigra) of rat brain and in the cell body, neurites, and growth cones of rat pheochromocytoma cells after treatment with nerve growth factor [1].
• Almost all principal ganglion cells were TH- and DBH-immunoreactive [2].
• From these results, it is presumed that bergenin and norbergenin may be the active components of Mallotus japonicus in inhibiting TH, and these inhibitory effects may be partially responsible for the clinical use of Mallotus japonicus in treating peptic ulcer by reducing the availability of dopa/dopamine in vivo [3].

High impact information on TH

• PM isolated from the adrenal cortex, kidney, and liver also induced TH in low density chromaffin cell cultures, although to a smaller extent than PM of the adrenal medulla [4].
• Since acetylcholinesterase was neither induced in high density nor in PM-treated low density cultures, an induction of TH as a result of a general increase in protein synthesis was excluded [4].
• Laminin increases both levels and activity of tyrosine hydroxylase in calf adrenal chromaffin cells [5].
• Laminin increases the levels of the enzymes tyrosine hydroxylase, dopamine-beta-hydroxylase, and phenylethanolamine-N-methyl-transferase [5].
• The effect of laminin can be blocked by antibodies directed against a fragment of the heparin-binding domain of the molecule, whereas antibodies directed against other fragments do not block the increase in tyrosine hydroxylase [5].

Biological context of TH

• This difference could result in an altered degree of regulation by posttranslational phosphorylation and also association to cell organelle membranes of bovine TH as compared with rat TH [6].
• The carboxy terminal region has been shown to make up the catalytic site of TH and, therefore, is conserved to a greater extent in different species than the amino terminal region, which has been shown to be mainly responsible for the regulation of the catalytic activity of TH [6].
• The predicted amino acid sequence of bovine TH is compared with that of rat TH and shows a similarity of 66% in the amino terminal (amino acids 1-157) and 91% in the carboxy terminal (amino acids 158-491) region of the TH protein molecule [6].
• The previously obtained cDNAs coding for bovine tyrosine hydroxylase (TH) mRNA (mRNATH) were further analyzed, and the entire nucleotide sequence was determined [6].
• The specific activity of tyrosine hydroxylase (TH) in bovine adrenal chromaffin cells can be controlled by changing cell density [7].

Anatomical context of TH

• Membranes prepared from lysed granules retain TH, whereas granule contents are free of the enzyme [8].
• Granule-associated TH sediments on continuous sucrose gradients with dopamine beta-hydroxylase, a marker for granule membranes, indicating that TH is associated with chromaffin granules [8].
• Intact secretory granules isolated from bovine adrenal medulla express tyrosine hydroxylase (TH) activity [8].
• Preparation of dissociated chromaffin cells from bovine adrenal medullae or the harvesting of cultured cells resulted in a rapid decrease of the specific mRNA(TH) (defined as the amount of mRNA(TH) (where TH represents tyrosine hydroxylase) per microgram of total RNA) [9].
• By contrast, TH from adrenal cytosol fractionated exclusively into the aqueous phase along with other soluble proteins [8].

Associations of TH with chemical compounds

• Three of the four serine residues (Ser 8, 19, and 40) that have been shown to be substrates for various protein kinases in rat TH are also present in bovine TH and are located near the amino terminal end of the molecule [6].
• All of the absent amino acid residues of bovine TH are missing from an alanine-rich region in the N-terminal portion of the rat and human proteins (amino acids 51-68) [10].
• Predicted amino acid sequence of bovine tyrosine hydroxylase and its similarity to tyrosine hydroxylases from other species [6].
• Chromaffin cells initially plated at low density (2-3 X 10(4) cells/cm2), and subsequently replated at a 10-fold higher density showed a sixfold increase in specific TH activity within 48 h, resulting from enhanced synthesis (increased number of TH molecules as demonstrated by immunotitration and blockade by cycloheximide) rather than activation [7].
• Since neither acetylcholinesterase nor lactate dehydrogenase specific activities were increased by high cell density, it can be concluded that the contact-mediated induction of TH is rather specific, and not the result of a general process of enzyme induction [7].

Regulatory relationships of TH

• DBH and PNMT appear to be regulated via the same mechanism as TH [11].
• The marginal effects of large doses of nicotine on both cAMP accumulation and TH induction were blocked completely by hexamethonium but were also partially inhibited by the VIP antagonist [p-chloro-D-Phe6,Leu17]-VIP [12].
• Neuropeptide Y inhibits chromaffin cell nicotinic receptor-stimulated tyrosine hydroxylase activity through a receptor-linked G protein-mediated process [13].
• The effect of IGF-I on high K(+)-stimulated tyrosine hydroxylase activity was measurable when enzyme activity was assayed in vitro, suggesting that this effect was due to a stable modification of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)[14]
• Both short- and long-term effects of nerve growth factor on tyrosine hydroxylase in calf adrenal chromaffin cells are blocked by S-adenosylhomocysteine hydrolase inhibitors [15].

Other interactions of TH

• The colocalization of DAT with tyrosine hydroxylase (TH) or dopamine beta hydroxylase (DBH) immunoreactivities was observed in nerve terminals [16].
• To determine whether angiotensin affects synthesis of catecholamines, the activities of TH and PNMT were examined [17].
• The presence of the phosphodiesterase inhibitor HL 725 further increased the stimulation of TH activity by PACAP, indicating that this activation was mediated via a cascade of events initiated by cAMP [18].
• Thus, the phosphorylation of TH in bovine chromaffin cells appears to be regulated at three sites by three separate intracellular signaling pathways--Ser19 via Ca2+/calmodulin-dependent protein kinase II; Ser31 via ERK (MAP2 kinases); and Ser40 via cAMP-dependent protein kinase [19].
• Treatment of membranes with a phosphatidylinositol-specific phospholipase C did not remove TH, ruling out the possibility of a glycosyl phosphatidyl anchor [8].

Analytical, diagnostic and therapeutic context of TH

• Comparison of the size of bovine and rat TH mRNA and protein by northern blot and immunoblot analyses yielded differences consistent with those predicted from the nucleotide sequence data [10].
• Site-directed mutagenesis showed that a TH mutant in which Ser-19 was substituted by Ala retained enzymatic activity at the same level as the non-mutated enzyme, but was a poor substrate for CaM kinase II and did not bind the 14-3-3 protein [20].
• Antibodies raised against PNMT and TH were used in an indirect immunofluorescence method [21].
• We conclude that the PAP method can be used for quantitative immunocytochemistry of brain TH providing that optimal reaction conditions are established [22].
• The activated TH with calpain II, characterized by high-performance gel permeation chromatography, had a reduced Mr of 120,000 from the Mr of 230,000 of native enzyme [23].

References