Modulation of phenylalanine and tyrosine concentrations by ischemia and guanosine in neuronal PC12 cells

Abstract

Survival of neurons is dependent on the presence of trophic and non-trophic factors. We have previously observed the protective capacity of purine nucleosides in hypoxic neuronal cell cultures. Guanosine appeared especially interesting with respect to its remarkable neurite-stimulating aptitude. Here we report the effect of ischemic stress and guanosine on the concentration of the essential amino acids phenylalanine and tyrosine, in culture supernatants of PC12 cells. In ischemic neuronal cultures, a substantial rise of phenylalanine and tyrosine levels was observed, indicating inhibition of cellular metabolism due to neuronal stress. Elevated phenylalanine and tyrosine concentrations were reduced by the addition of guanosine. Guanosine even down-regulated the ratio of phenylalanine to tyrosine. Results may support current efforts to propagate guanosine as a neuroprotective and neuroregenerative substance.

Keywords

• guanosine
• ischemia
• phenylalanine
• phenylalanine-4-hydroxylase
• pc12 cells
• purine nucleosides
• tyrosine