Influence of 7,8 Dihydroneopterin and Hyperoxia on Neurite Growth and Tyrosine Hydroxylase Activity of PC 12 Cells

Abstract

The influence of dihydroneopterin on tyrosine hydroxylase activity in PC 12 cells was investigated under normoxic and hyperoxic conditions, and with or without iron ions in the incubation medium. Low dihydroneopterin concentrations as well as hyperoxia increase tyrosine hydroxylase activity. Due to a too vigorous radical formation, high dihydroneopterin concentrations lead to a decrease of tyrosine hydroxylation in normoxic state and even more strongly in hyperoxic state. Similar depression of tyrosine hydroxylase activity was seen after addition of iron ions, which can form hydroxyl radicals by a Fenton type reaction. As higher iron concentrations in combination with dihydroneopterin do not suppress tyrosine hydroxylase activity completely, we conclude that dihydroneopterin and iron ions react with each other resulting in neutralisation of their effects. In conclusion, 7,8 dihydroneopterin can modulate tyrosine hydroxylase activity and its effects are dependent on concentration of oxygen as well as presence or absence of iron ions.

Keywords

• tyrosine hydroxylase: tyrosine-3-hydroxylase
• lyrosine-3-monooxygenase (ec 1.14.16.4)
• dihydropteridine reductase: quinonoid dihydropteridine reductase (ec 1.66.99.7)
• dopa -decarboxylase: (ec 4.1.1.28)
• dopamine- β -hydroxylase: dopamine- β -monooxygenase (ec 1.14.17.1)
• monoaminooxidase: tyraminase (ec 1.4.3.4)