Summary
Tyrosine hydroxylase (TH) contents in the caudate nucleus, putamen, and substantia nigra from control and parkinsonism brains were measured for the first time by a sandwich enzyme immunoassay. Both the TH protein content and TH activity (Vmax) were decreased in parallel in the parkinsonian brains as compared with those of the control brains. In contrast, TH “homospecific activity” (activity per enzyme protein) was significantly increased in the parkinsonian brains. The results indicate that the decrease of TH activity in parkinsonian brains is due to the decrease of TH protein content as a result of cell death. The increase in the “homospecific activity” of residual TH in parkinsonian brain suggests such molecular changes in TH molecules as result in a compensatory increase in TH activity.
Similar content being viewed by others
References
Elsworth JD, Deutch AY, Redmond Jr DE, Sladek Jr JR, Roth RH (1987) Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on catecholamines and metabolites in primate brain and CSF. Brain Res 415: 293–299
Grima B, Lamouroux A, Bori C, Julien J-F, Javoy-Agid F, Mallet J (1987) A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics. Nature 326: 707–711
Hornykiewicz O (1966) Dopamine (3-hydroxytyramine) and brain function. Physiol Rev 18: 925–964
Kaneda N, Kobayashi K, Ichinose H, Kishi F, Nakazawa A, Kurosawa Y, Fujita K, Nagatsu T (1987) Isolation of a novel cDNA clone for human tyrosine hydroxylase: alternative RNA splicing produces four kinds of mRNA from a single gene. Biochim Biophys Res Commun 146: 971–975
Kojima K, Mogi M, Oka K, Nagatsu T (1984) Purification and immunochemical characterization of human adrenal tyrosine hydroxylase. Neurochem Int 6: 475–480
Lloyd KG, Davidson L, Hornykiewicz O (1975) The neurochemistry of Parkinson's disease: effect of L-dopa therapy. J Pharm Exp Ther 195: 453–464
McGeer PL, McGeer EG (1976) Enzymes associated with the metabolism of catcholamines, acetylcholine and GABA in human controls and patients with Parkinsons's disease and Huntington's chorea. J Neurochem 26: 65–76
Mogi M, Kojima K, Nagatsu T (1984) Detection of inactive or less active form of tyrosine hydroxylase in human adrenals by a sandwich enzyme immunoassay. Anal Biochem 138: 125–132
Mogi M, Kojima K, Harada M, Nagatsu T (1986) Purification and immunochemical properties of tyrosine hydroxylase in human brain. Neurochem Int 8: 423–428
Mogi M, Harada M, Kojima K, Kiuchi K, Nagatsu I, Nagatsu T (1987) Effects of repeated systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and tyrosine hydroxylase content. Neurosci Lett 80: 213–218
Nagatsu T (1975) Biosynthesis and metabolism of dopamine period. No to Shinkei 27: 1249–1260
Nagatsu T, Kato T, Numata (Sudo) Y, Ikuta K, Sano M, Nagatsu I, Kondo Y, Inagaki S, Iizuka R, Hori A, Narabayashi H (1977) Phenylethanolamine N-methyltransferase and other enzymes of catecholamine metabolism in human brain. Clin Chim Acta 75: 221–232
Nagatsu T, Oka K, Kato T (1979) Highly sensitive assay for tyrosine hydroxylase activity by high-performance liquid chromatography. J Chromatogr 163: 247–252
Riederer P, Rausch W-D, Birkmayer W, Jellinger K, Seemann D (1978) CNS modulation of adrenal tyrosine hydroxylase in Parkinson's disease and metabolic encephalopathies. J Neural Transm [Suppl] 14: 121–131
Rush RA, Kindler SH, Udenfriend S (1974) Homospecific activity, an immunological index of enzyme homogeneity; changes during the purification of dopamine β-hydroxylase. Biochem Biophys Res Commun 61: 38–44
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mogi, M., Harada, M., Kiuchi, K. et al. Homospecific activity (activity per enzyme protein) of tyrosine hydroxylase increases in parkinsonian brain. J. Neural Transmission 72, 77–82 (1988). https://doi.org/10.1007/BF01244634
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01244634