Untersuchungen zur Zink-modulierten Signaltransduktion in Säugerzellen: Die Auswirkungen von Signalwegen auf die Zinkhomöostase.

Zinc, as a divalent cation, is an essential trace element and fulfils a regulatory function in a frequently growing number of proteins. Because zinc is known to directly regulate and modulate the activity of transcription factors and enzymes as well as playing a crucial role in differentiation, proliferation and apoptotic cell death, a second messenger function for this metal ion has been discussed. For this reason the present work addresses the influence of zinc ions on intracellular signal transduction pathways. Major emphasis was put on enzyme-modulated zinc im- and export mechanisms as well as the initiation of programmed cell death in C6 rat glioma cells. Studies focused on intracellular signal transduction pathways identified phoshodiesterases and the phospholipase C to be involved in cellular zinc in- and efflux. Furthermore the extent of cAMP- and PKA-participation in cellular zinc transport is still questionable but involvement of cGMP, calcium, protein kinase C and G as well as the guanylate cyclase could be excluded in this context. Additionally C6 cells were examined with regard to the existence of a zinc-binding, extracellular cell-surface receptor which is specifically activated by zinc ions and might influence the intracellular zinc homeostasis by releasing calcium ions from cytosolic stores. Studies with C6 cells showed, in contrast to A459 cells (human lung carcinoma cells), no evidence for the so-called zinc-sensing receptor . Methodical results of the present work showed that S-nitroso-compounds have the ability to extract zinc ions from the previously formed zinc/Zinquin-complex. Furthermore the results of chromatographic and spectrographic studies of the PLC-activator m-3M3FBS lead to an exclusion of this component from fluorimetric studies due to its emitted auto-fluorescence and decay induced by UV-light.