title: c-Jun N-terminal kinase (JNK) and JNK interacting protein response in rat brain after transient middle cerebral artery occlusion.
abstract: c-Jun response is involved in the development of ischemic brain injury, which is activated by c-Jun N-terminal kinase-1 (JNK-1). The activity of JNK-1 is strictly regulated, and only the phosphorylated form of JNK (phospho-JNK) which is translocated to the nucleus has an ability to activate c-Jun response. There is a protein which inhibits JNK-1 activation, and known as JNK interacting protein-1 (JIP-1). In this study, we investigated change in JNK-1, phospho-JNK, and JIP-1 immunoreactivity in rat brain after transient middle cerebral artery (MCA) occlusion. Immunoreactive JNK-1 was scant in the sham-control brain, but it was induced at 1 h after reperfusion, which was slightly increased at 3 h of reperfusion. By contrast, phospho-JNK remained negative till 3 h. At 8 h, JNK-1 and phospho-JNK became distinctly positive, and nuclei as well as cytoplasm were stained. Thereafter, immunoreactivity for JNK-1 and phospho-JNK became furthermore dense, and most neurons revealed positively stained nuclei. Immunoreactivity for JIP-1 remained negative till 8 h of reperfusion, but at 24 and 72 h, cytoplasm of cortical neurons at the MCA boundary area was positively stained. This JIP-1 induction got behind the JNK-1 activation, and therefore, may be a vain effort for neurons to survive. Inhibition of JNK-1 activation might become an innovative means of therapy for stroke treatment in the future.
authors.affiliation: Department of Neurology, Okayama University Medical School, 2-5-1 Shikata-machi, 700-8558, Okayama, Japan. thayashi@cc.okayama-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Sakai
authors.forename: C
authors.initials: C
authors.lastname: Sasaki
authors.forename: W R
authors.initials: WR
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Warita
authors.forename: K
authors.initials: K
authors.lastname: Abe
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002536:Cerebral Arteries / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D004790:Enzyme Induction; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D013997:Time Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C110528:Mapk8ip1 protein, rat; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases