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Activation of c‐Jun in the nuclei of neurons of the CA‐1 in thrombin preconditioning occurs via PAR‐1
Author(s) -
Price Melanie,
Badaut Jérôme,
Thevenet Jonathan,
Hirt Lorenz
Publication year - 2009
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22299
Subject(s) - thrombin , phosphorylation , c jun , agonist , kinase , chemistry , microbiology and biotechnology , hippocampal formation , in vivo , receptor , in vitro , transcription factor , biology , neuroscience , biochemistry , immunology , platelet , gene
Recently it has been shown that the c‐Jun N‐terminal kinase (JNK) plays a role in thrombin preconditioning (TPC) in vivo and in vitro. To investigate further the pathways involved in TPC, we performed an immunohistochemical study in hippocampal slice cultures. Here we show that the major target of JNK, the AP‐1 transcription factor c‐Jun, is activated by phosphorylation in the nuclei of neurons of the CA1 region by using phospho‐specific antibodies against the two JNK phosphorylation sites. The activation is early and transient, peaking at 90 min and not present by 3 hr after low‐dose thrombin administration. Treatment of cultures with a synthetic thrombin receptor agonist results in the same c‐Jun activation profile and protection against subsequent OGD, both of which are prevented by specific JNK inhibitors, showing that thrombin signals through PAR‐1 to JNK. By using an antibody against the Ser 73 phosphorylation site of c‐Jun, we identify possible additional TPC substrates. © 2009 Wiley‐Liss, Inc.