BACKGROUND: Modulation of the inflammatory stress response by anesthesia may be responsible for an increased susceptibility to infectious complications, such as wound infection or pneumonia. Sevoflurane, a specific inhibitor of activator protein-1, an immediate early transcription factor, induces apoptosis in T-cells. Because p38 can be involved either in pro- or antiapoptotic processes, we examined whether the sevoflurane-induced apoptosis is mediated by p38 activation in Jurkat T-cells. METHODS: Jurkat T-cells were exposed to different concentrations of sevoflurane, isoflurane, or desflurane in vitro. Phosphorylation of mitogen-activated protein (MAP) kinases, upstream kinases, downstream activating transcription factor 2 ATF-2, and caspase-3 processing were evaluated by Western blot. p38 kinase activity was evaluated after immunoprecipitation and phosphorylation of the substrate ATF-2 using Western blot. Apoptosis was assessed using flow cytometry after staining with green fluorescent protein-annexin V. RESULTS: While desflurane had no effect, sevoflurane and isoflurane induced p38 phosphorylation with sevoflurane inducing p38 kinase activity. Sevoflurane did not affect the MAP kinases ERK and JNK. Sevoflurane exposure also induced phosphorylation of apoptosis signal-regulating kinase-1 (ASK1), MAP kinase kinases 3 and 6 (MKK3/MKK6), and ATF-2. Pretreatment of cells with the general caspase inhibitor Z-VAD.fmk did not prevent the sevoflurane-induced phosphorylation of p38. Isoflurane- and sevoflurane-mediated caspase-3 processing and apoptosis could not be abolished by pretreatment with the specific p38 inhibitors SB202190 and SB203580. CONCLUSIONS: Sevoflurane is a specific activator of the apoptosis signal-regulating kinase-1-, MKK3/MKK6-p38 MAP kinase cascade in Jurkat T-cells. Our data suggest that sevoflurane-induced p38 activation is not affected by caspase activation. Furthermore, sevoflurane-induced apoptosis is not dependent on p38 MAP kinase activation.
BACKGROUND: Modulation of the inflammatory stress response by anesthesia may be responsible for an increased susceptibility to infectious complications, such as wound infection or pneumonia. Sevoflurane, a specific inhibitor of activator protein-1, an immediate early transcription factor, induces apoptosis in T-cells. Because p38 can be involved either in pro- or antiapoptotic processes, we examined whether the sevoflurane-induced apoptosis is mediated by p38 activation in Jurkat T-cells. METHODS: Jurkat T-cells were exposed to different concentrations of sevoflurane, isoflurane, or desflurane in vitro. Phosphorylation of mitogen-activated protein (MAP) kinases, upstream kinases, downstream activating transcription factor 2 ATF-2, and caspase-3 processing were evaluated by Western blot. p38 kinase activity was evaluated after immunoprecipitation and phosphorylation of the substrate ATF-2 using Western blot. Apoptosis was assessed using flow cytometry after staining with green fluorescent protein-annexin V. RESULTS: While desflurane had no effect, sevoflurane and isoflurane induced p38 phosphorylation with sevoflurane inducing p38 kinase activity. Sevoflurane did not affect the MAP kinases ERK and JNK. Sevoflurane exposure also induced phosphorylation of apoptosis signal-regulating kinase-1 (ASK1), MAP kinase kinases 3 and 6 (MKK3/MKK6), and ATF-2. Pretreatment of cells with the general caspase inhibitor Z-VAD.fmk did not prevent the sevoflurane-induced phosphorylation of p38. Isoflurane- and sevoflurane-mediated caspase-3 processing and apoptosis could not be abolished by pretreatment with the specific p38 inhibitors SB202190 and SB203580. CONCLUSIONS:Sevoflurane is a specific activator of the apoptosis signal-regulating kinase-1-, MKK3/MKK6-p38 MAP kinase cascade in Jurkat T-cells. Our data suggest that sevoflurane-induced p38 activation is not affected by caspase activation. Furthermore, sevoflurane-induced apoptosis is not dependent on p38 MAP kinase activation.
Authors: Yuanlin Dong; Guohua Zhang; Bin Zhang; Robert D Moir; Weiming Xia; Edward R Marcantonio; Deborah J Culley; Gregory Crosby; Rudolph E Tanzi; Zhongcong Xie Journal: Arch Neurol Date: 2009-05
Authors: Paul E Polak; Randall O Dull; Sergey Kalinin; Anthony J Sharp; Richard Ripper; Guy Weinberg; David E Schwartz; Israel Rubinstein; Douglas L Feinstein Journal: J Neuroinflammation Date: 2012-12-19 Impact factor: 8.322