Submitted to: Keystone Symposia
Publication Type: Abstract Only
Publication Acceptance Date: November 18, 2005
Publication Date: January 30, 2006
Citation: Li, C., Elsasser, T.H. 2006. Growth hormone effects in immune stress: AKT/ENOS signaling module in the cellular response [abstract]. Keystone Symposia, Signaling Networks. Abstract Book p.43.
The activation of the constitutive endothelial nitric-oxide synthase (eNOS) and expression of inducible NOS (iNOS) and subsequent nitric oxide production are among the early cellular responses following exposure of animals (bovine) to lipopolysaccharide (LPS). On the other hand, growth hormone (GH) exerts many effects in addition to its ability to stimulate growth. It has been observed in our laboratory the effects of GH administration on components of the NO generating cascade to account for increases in NO production and protein nitration following an immune challenge indicating the cross-talking between multiple signaling pathways. However, the critical signal transduction affecting the cell response to immune stress remains unclear in vivo. In the present study, we have employed animal models (calves) challenged with low-level endotoxin (LPS) to examine the role of eNOS in the immune stress. Moreover, we have used established bovine cell lines (MDBK) to dissect the mechanisms underlying GH/LPS-stimulated eNOS activity and the pro-inflammatory role for eNOS. Phosphorylation of eNOS appeared 15 to 30 min after GH treatment of GH and was saturated at about 75 min and secondary administration of GH had no effects on the level of phosphyrylation of eNOS. Inhibiting the AKT activity reduced/eliminated the activation (phosphorylation) of eNOS. Using specific AKT inhibitor and functional proteomic approach, we were able to detect the activities of multiple potential signal transduction pathway elements, the downstream targets of AKT pathway and the modification of those responses by treatment of GH. Combining the data from the animal model, in vitro experiments, as well as the functional proteomic analysis, we propose that AKT/eNOS signaling module may function as a potential feedback loop in GH signal pathway.