Reactive oxygen species regulate swelling-induced taurine efflux in NIH3T3 mouse fibroblasts.
NIH3T3 mouse fibroblasts generate reactive oxygen species (ROS) and release taurine following exposure to hypotonic medium and to isotonic medium containing the lipase activator melittin. The swelling-induced taurine release is potentiated by H2O2, the calmodulin antagonist W7, and ATP, but inhibited by the antioxidant butulated hydroxytoluene (BHT), the NAD(P)H oxidase inhibitor diphenylene iodonium (DI), and the iPLA2 inhibitor bromoenol lactone (BEL). The swelling-induced ROS production is also inhibited by BHT and BEL. H2O2 does not affect the volume set point for activation of the volume-sensitive taurine efflux. The 5-lipoxygenase (5-LO) inhibitor ETH 615-139 impairs the swelling-induced taurine efflux in the absence as well as in the presence of H2O2. The melittin-induced taurine release is, in analogy with the swelling-induced taurine release, potentiated by H2O2 and inhibited by BHT, DI, BEL, ETH 615-139 and anion channel blockers. Thus, swelling- and melittin-induced cell signalling and taurine release involve joint elements. The swelling-induced taurine efflux is potentiated by the protein tyrosine phosphatase inhibitor vanadate, and the potentiating effect of H2O2 and vanadate is impaired in the presence of protein tyrosine kinase inhibitor genistein. It is suggested that (i) iPLA2 and 5-LO activity is required for the swelling-induced activation of taurine efflux from NIH3T3 cells, (ii) ROS are produced subsequent to the PLA2 activation by the NAD(P)H oxidase complex, and (iii) ROS inhibit a protein tyrosine phosphatase (PTP1B) causing a potentiation of the swelling-induced taurine release.
Lambert
I H
IH
The August Krogh Institute, Biochemical Department, Universitetsparken 13, DK-2100, Copenhagen O, Denmark. ihlambert@aki.ku.dk
D016475:3T3 Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D054522:Group VI Phospholipases A2; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006861:Hydrogen Peroxide; D008555:Melitten / Q000494:pharmacology; D051379:Mice; D009995:Osmosis / Q000187:drug effects / Q000502:physiology; D009997:Osmotic Pressure / Q000187:drug effects; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013654:Taurine / Q000493:pharmacokinetics*
D000975:Antioxidants; D017382:Reactive Oxygen Species; D013654:Taurine; D008555:Melitten; D006861:Hydrogen Peroxide; D001094:Arachidonate 5-Lipoxygenase; D010741:Phospholipases A; D054522:Group VI Phospholipases A2; D054467:Phospholipases A2; C516476:Pla2g6 protein, mouse