Elzbieta Rebas, Jowita Rzajew and Bozena Ferenc
Medical University of Lodz, Poland
Posters & Accepted Abstracts: J Neurol Neurophysiol
Many neurodegenerative and affective diseases are related to disturbed metabolism of γ- aminobutyric acid (GABA) and GABA-shunt enzymes: glutamate decarboxylase (GAD), GABA aminotransferase (GABA-T) and succinate-semialdehyde dehydrogenase (SSADH). Neurological diseases are also often accompanied by impaired calcium conditions. Traditional drugs are not always efficient and may evoke adverse side effects. Chemicals naturally occurring in plants can provide an attractive alternative target in modulating of neurotransmission via affecting of GABA-shunt enzymes activity. The aim of this study was to investigate an effect of selected phytochemicals: genistein and zeaxanthin on activity of GABA-shunt enzymes. In our study we used stably transfected pseudoneuronal PC12 cells with reduced expression of neuron-specific isoforms of calcium membrane pumps: PMCA2 or PMCA3 and increased intracellular calcium concentration. Cells were incubated with 10 μM and 20 μM of tested compounds during 10 and 20 minutes, a short time precluding genomic action or during 4 and 12 hours. Enzymes activity was determined with fluorimetric and spectrophotometric methods. Additionaly, during GAD activity determination we used vigabatrin, inhibitor of GABA-T. Our results indicate that genistein and zeaxhantin can modulate activity of GABA-shunt, especially glutamate decarboxylase and this way change balance between to oppositely acting neurotransmitters. Genistein decreases GAD activity in all studied lines, but cells with reduced expression of PMCA are more sensitive to genistein. Zeaxhantin inhibits GAD under disturbed calcium homeostasis but increases GAD activity in normal cells. Due to short time of incubation we suggest non-genomic action of studied phytochemicals.
Elzbieta Rebas has completed her PhD and DSc from Medical University of Lodz. Currently she is an Associate Professor of Department of Molecular Neurochemistry at Medical University of Lodz. She has published a number of papers related to brain function in reputed international journals and participated in many international conferences, congresses and symposia. She has more than 20 years of teaching experience in the field of Biochemistry. She is a Member of FEBS and Council of Polish Biochemical Society.
E-mail: [email protected]