Change of tyrosine hydroxylase in the parkinsonian brain and in the brain of MPTP-treated mice as revealed by homospecific activity.
Changes in homospecific activity (unit of enzyme activity per unit of enzyme protein; Rush, Kindler and Udenfriend, 1974. Biochem. Biophys. Res. Commun., 61, 38) of tyrosine hydroxylase (TH) in the striatum of the brain were examined in MPTP-treated mice and parkinsonian patients. After a single injection of MPTP to mice, TH activity was acutely inhibited only in situ without changes in in vitro TH activity (Vmax) and TH protein; TH homospecific activity (TH Vmax/TH protein) did not change. After repeated injection of MPTP to mice for 8 days, in situ TH activity, in vitro TH Vmax, and TH protein were decreased in parallel, and TH homospecific activity did not change. The result indicates that the decreases in in situ TH activity and in TH Vmax are due to the decrease in TH protein by nerve degeneration of dopaminergic neurons in MPTP treated mice. However, when MPP+ was infused in the striatum of rats for 3 hours, in vitro TH activity (Vmax) was decreased without changes in TH protein. Thus, TH homospecific activity was decreased. The results indicate that MPP+ inactivates TH protein in the striatum after continued infusion. In contrast, the homospecific activity of Th in post-mortem parkinsonian striatum was increased 3-fold. The increase in homospecific activity of residual TH in parkinsonian brain suggests such molecular changes in TH molecules as result in a compensatory increase in TH activity.
Nagatsu
T
T
Department of Biochemistry, Nagoya University School of Medicine, Japan.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D051379:Mice; D010300:Parkinson Disease / Q000201:enzymology*; D010302:Parkinson Disease, Secondary / Q000201:enzymology; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium