Changes in Ca2+ concentration in phorbol ester and thapsigargin treated glioma C6 cells. The role of protein kinase C in regulation of Ca2+ entry.
Glioma C6 cells treated with 12-0-tetradecanoyl-phorbol-13-acetate, TPA (10 nM and 100 nM) manifested slow increase in intracellular calcium concentration ([Ca2+]i), dependent upon both Ca2+ release from intracellular stores and Ca2+ entry, and ranging from 50 to 500 nM in different cells. The effect of TPA was abolished by the down-regulation procedure and by protein kinase C inhibitors, such as staurosporine (100 nM), suramin (100 microM), and sphingosine (100 microM), pointing to a role of protein kinase C (PKC) in this process. On the other hand, thapsigargin (100 nM), a selective inhibitor of the endoplasmic reticulum Ca(2+)-ATPase, produced a rapid increase in [Ca2+]i (up to 800 nM). This increase consisted of a transient initial phase followed by sustained elevation in [Ca2+]i, typical of Ca2+ release from intracellular stores and of Ca2+ entry, respectively. However, when the cells were exposed to TPA (100 nM) prior to thapsigargin (100 nM), then thapsigargin produced only a transient rise in [Ca2+]i. We suggest that TPA, a PKC activator, affects thapsigargin-induced Ca2+ entry, probably by PKC-mediated changes in cytoskeleton structures.
Barańska
J
J
Nencki Institute of Experimental Biology, Department of Cellular Biochemistry, Warsaw, Poland.
Chaban
V
V
Czarny
M
M
Sabała
P
P
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D005910:Glioma / Q000473:pathology*; D051379:Mice; D009363:Neoplasm Proteins / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology*; D015398:Signal Transduction; D013729:Terpenes / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D019284:Thapsigargin; D014407:Tumor Cells, Cultured / Q000187:drug effects
D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D013729:Terpenes; D019284:Thapsigargin; D011493:Protein Kinase C; D000252:Calcium-Transporting ATPases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium