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Tyrosine Hydroxylase Activity in Caudate Nucleus from Parkinson's Disease: Effects of Iron and Phosphorylating Agents
Author(s) -
Rausch WolfDieter,
Hirata Yoko,
Nagatsu Toshiharu,
Riederer Peter,
Jellinger Kurt
Publication year - 1988
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1988.tb13250.x
Subject(s) - caudate nucleus , tyrosine hydroxylase , endocrinology , medicine , stimulation , phosphorylation , dopamine , specific activity , enzyme assay , chemistry , gerbil , biology , enzyme , biochemistry , ischemia
Tyrosine hydroxylase (TH) activity of human postmortem brain tissues from controls and patients with Parkinson's disease (PD) was examined in the presence of Fe 2+ and phosphorylation agents, such as cyclic AMP, exogenous protein kinase, calcium plus calmodulin (Ca 2+ ‐CaM), and ATP. TH activity from parkinsonian tissue was increased by 48% with statistical significance in the presence of exogenous protein kinase. Cyclic AMP alone had no effect, whereas Ca 2+ ‐CaM increased the activity by only 10%. The presence of acetylcholine resulted in a slight decrease in enzyme activity. Human TH was stimulated 13.17‐fold in the presence of 1 m M Fe 2+ . For iron dependence, no significant differences could be shown for the K m values of TH in striata of PD, while the activity of TH was half of that of controls. Here stimulation with 1 m M Fe 2+ raised the activity of TH 11‐fold. Stimulation of rat, gerbil, pig, and human caudate nucleus TH with Fe 2+ shows remarkable species differences. In particular, the sensitivity of human TH to stimulating processes is noteworthy. H 2 O 2 decreases TH activity only at high concentrations. Species differences are noted for the combined incubation of Fe 2+ and H 2 O 2 . In the gerbil caudate nucleus, H 2 O 2 does not prevent the stimulating properties of Fe 2+ , while the pig shows a dose‐dependent decline of TH activity. In conclusion, there are no significant changes in the stimulating properties of human caudate nucleus TH activity with Fe 2+ in PD, while such differences are noted by using exogenous protein kinase. Furthermore, experimental evidence shows that TH activity declines at high concentration of H 2 O 2 only. Potentiation of this effect by Fe 2+ seems to be species‐dependent.