In vivo stress activates JAK-STAT in liver but not brain.
Miller-DB; Benkovic-SA; O'Callaghan-JP
Toxicologist 2002 Mar; 66(1-S):218-219
The Janus kinase-signal transducers and activators of transciption (JAK-STAT) signaling pathways are believed to be crucial signalling pathways in the physiological changes induced by stress. Various stressors (e.g., UV) have been shown to activate the JAK-STAT pathway, in vitro, but only a few reports have examined the JAK-STAT pathway using stress models, in vivo. Here C57BL6/J female mice were exposed to restraint, vibration or cold stress. To preserve steady-state phosphorylation, the mice were killed by focused microwave irradiation. The activation state of STAT 3, 5 and 6 was assessed from blots of tissue homogenates probed with phospho state-specific antibodies as well as antibodies directed against the context-independent state of the various STATs to assess their total tissue levels. Quantification was achieved by densitometry of bands generated by enhanced chemiluminescence. No changes in the activation (phosphorylation) state of any of the STATs were evident in brain; however, large increases in phosphoSTAT3 were evident in liver, with restraint and cold providing the largest magnitude changes (approximately 300%). STAT3 levels did not change with any of the stressors. Restraint of adrenalectomized mice caused an even larger increase in phosphoSTAT3 (approximately 500%). Immunohistochemical examination of STAT3 confirmed that restraint resulted in the nuclear location (i.e. activation) of STAT3, which was substantially greater in adrenalectomized mice. These data suggest that effects of physiological stressors are mediated through a STAT3 pathway that may involve the HPA axis and/or sympathetic nervous system.
Stress; In-vivo-study; Animal-studies; Vibration; Tissue-culture; Brain-function; Liver-function; Laboratory-animals; Physical-stress; Physiological-stress; Physiology
The Toxicologist. Society of Toxicology 41st Annual Meeting and ToxExpo, March 17-21, 2002, Nashville, Tennessee