Inhibition of ERK and JNK decreases both osmosensitive taurine release and cell proliferation in glioma cells.
Cell swelling is associated with the activation of an increase in the osmosensitive taurine release (OTR) rate, which serves to decrease cell volume as part of a process known as regulatory volume decrease. OTR, which is sensitive to many pharmacological agents including anion channel blockers and signalling pathway modulators, has also been suggested to play a role in cell cycle progression. At non-cytotoxic concentrations, the anion channel blocker NPPB (25 microM), the extra-cellular signal-regulated kinase inhibitor PD98059 (50 microM), and the c-Jun NH2-terminal kinase inhibitor SP 600125 (5 microM) each decreased the OTR rate by > or =50%, decreased cell proliferation, and increased G0/G1 cell cycle arrest.
Belsey
Mark J
MJ
Department of Pharmacology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK. mjbelsey@bristolalumni.org.uk
Davies
Andrew R L
AR
Witchel
Harry J
HJ
Kozlowski
Roland Z
RZ
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001254:Astrocytoma / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D001728:Dicumarol / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D005419:Flavonoids / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D007473:Ion Channels / Q000037:antagonists & inhibitors; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D009336:Necrosis / Q000209:etiology; D009544:Niflumic Acid / Q000494:pharmacology; D009579:Nitrobenzoates / Q000494:pharmacology; D009994:Osmolar Concentration; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D013654:Taurine / Q000378:metabolism*
D000873:Anthracenes; D005419:Flavonoids; D007093:Imidazoles; D007473:Ion Channels; D009579:Nitrobenzoates; D011725:Pyridines; D013654:Taurine; C432165:pyrazolanthrone; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D009544:Niflumic Acid; D001728:Dicumarol; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C093642:SB 203580; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one