Crucial role of c-Jun NH2-terminal kinase 1 (JNK1) in cold-restraint stress-induced gastric lesions in mice.
c-Jun NH2-terminal kinase 1 /JNK1, is activated in response to a broad array of cellular stresses. We investigated the role of JNK1 in the pathophysiology of cold-restraint stress-induced gastric lesions in mice. B6/129, wild type (WT) mice, or mutant mice deficient in Jnk1 (Jnk1-/- mice) were exposed to cold-restraint stress for different time periods. Gastric lesions were identified and quantitated by morphometric analysis. JNK1 activity in mucosal homogenates was quantitated by immunoprecipitation and in-vitro kinase assays. JNK1 expression and Akt activation were assessed by Western blots with anti-JNK1 and anti-phospho Akt antibodies, respectively. Gastric mucosal homogenates from Jnk1-/- mice exhibited no significant expression of JNK1 and no detectable level of JNK1 activation. Exposure of WT mice to cold-restraint stress led to the development of significant gastric lesions and to a greater than three-fold induction in JNK1 activity, while no lesions were detected in the gastric mucosa of Jnk1-/- mice. Since cold-restraint stress-induced gastric lesions involve the activation of cholinergic pathways, we tested the effect of atropine on both the development of gastric lesions and JNK1 activation. Pretreatment of WT mice with atropine completely inhibited both cold-restraint stress-induced lesions and JNK1 activation. Cold-restraint stress induced protein kinase B/Akt to a similar level in the gastric mucosa of both WT and Jnk1-/- mice indicating the integrity of other signaling pathways. JNK1 plays a key role in the development of cold-restraint stress-induced gastric lesions in mice through the activation of cholinergic, atropine sensitive pathways.
Kasugai
K
K
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0682, USA.
Watson
S J
SJ
A Flavell
R
R
J Davis
R
R
Todisco
A
A
D000818:Animals; D003080:Cold Temperature / Q000009:adverse effects*; D005753:Gastric Mucosa / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D048055:Mitogen-Activated Protein Kinase 8 / Q000502:physiology*; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000503:physiopathology*; D013315:Stress, Psychological / Q000503:physiopathology*
D048055:Mitogen-Activated Protein Kinase 8