Zinc homeostasis in C6 glioma cells: phospholipase C activity regulates cellular zinc export.
Zinc homeostasis in mammalian cells is precisely regulated by cellular signal transduction mechanisms. The main result of this study is the finding that modulators of phospholipase C (PLC) activity affect cellular zinc export. Two different PLC inhibitors caused an increase of the total cellular zinc level whereas two different PLC activators caused a decrease. Furthermore, both the inhibition of cyclic nucleotide phosphodiesterases as well as the administration of 8-bromo-cAMP evoked a drop in the intracellular zinc level, indicating the involvement of cAMP in the control of cellular zinc export. It is concluded that the activity of PLC controls cellular zinc transport and that the effect of elevated zinc concentrations on PLC activity might be mediated by cAMP. However, modulation of other major signaling enzymes did not affect the cellular zinc homeostasis. These include activation and inhibition of guanylate cyclase, activation of protein kinase G, activation of protein kinase A, and activation or inhibition of protein kinase C. Furthermore there was no evidence for the existence of a zinc-sensing receptor in C6 glioma cells, which would stimulate PLC activity and evoke a mobilization of intracellular free-calcium levels.
Jansen
Sven
S
Center for Biomolecular Interactions, University of Bremen, Leobener Str. NW2, 28359 Bremen, Germany.
Arning
Jürgen
J
Beyersmann
Detmar
D
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000037:antagonists & inhibitors; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D005910:Glioma / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology
D009569:Nitric Oxide; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D017869:Cyclic GMP-Dependent Protein Kinases; D011493:Protein Kinase C; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D015032:Zinc; D002118:Calcium