Wolf‐Dieter ‐D Rausch, Yoko Hirata, Toshiharu Nagatsu, Peter Riederer, Kurt Jellinger
Journal of Neurochemistry 50(1) 202-208 1988年1月1日 査読有り
Abstract: 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 mM 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 mM 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. Copyright © 1988, Wiley Blackwell. All rights reserved