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Restraint stress causes phosphorylation of STAT3 in liver of C57BL/6J mice through activation of adrenergic receptors.

Turner-JR; Benkovic-SA; O'Callaghan-JP; Miller-DB
Toxicologist 2007 Mar; 96(1):203
Psychological stress elicits two classical responses: 1) it activates the hypothalamicpituitary- adrenal axis, resulting in the release of glucocorticoids, and 2) it activates the sympathetic nervous system, which results in the release of norepinephrine and epinephrine. Although these two systems often work in tandem, our studies indicate that activation of the JAK-STAT signaling pathways in livers of mice subjected to restraint stress is solely controlled through the adrenergic stress response. Using a combination of focused-microwave irradiation to preserve protein phosphorylation state, and phospho-specific immunoblotting, we observed a 10-fold increase in PSTAT3tyr705 in the livers of mice restrained for two hours. This effect could be blocked by both alpha and beta adrenergic antagonists, but not by adrenalectomy. Additionally, alpha and beta adrenergic agonists (phenylephrine 10 mg/kg or isoproterenol 10 mg/kg s.c., respectively) mimic the stress response in vivo and trigger phosphorylation of liver STAT3. This activation appears to be controlled through the beta-adrenergic receptor, since blocking this receptor precludes PSTAT3 induction upon administration of phenylephrine, an alpha-adrenergic agonist. Histological analysis of livers from saline and phenylephrine treated mice showed a translocation of STAT3 from cytoplasm to the nucleus, respectively, and a blockade of translocation by propranolol pretreatment. Altogether, these data suggest that restraint stress triggers phosphorylation of liver STAT3 through a solely adrenergic pathway, which initially requires beta-adrenergic receptor activation. These findings support the idea the acute psychological stress can elicit STAT3 activation in the liver, and may therefore have ramifications on liver diseases or in modulating hepatotoxicity.
Biodynamics; Stress; Physical-stress; Psychological-stress; Psychological-reactions; Nervous-system-function; Liver-function; Animal-studies; Liver-disorders; Hepatic-microsomal-enzymes; Hepatotoxicity
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The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina