Increased expression of phosphorylated c-Jun amino-terminal kinase and phosphorylated c-Jun in human cerebral aneurysms: Role of the c-Jun amino-terminal kinase/c-Jun pathway in apoptosis of vascular walls

Yasushi Takagi*, Masatsune Ishikawa, Kazuhiko Nozaki, Shinichi Yoshimura, Nobuo Hashimoto, J. Paul Elliott, Issam A. Awad, Gary K. Steinberg, R. Loch Macdonald, Maciej S. Lesniak, Daniele Rigamonti

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

OBJECTIVE: Vascular remodeling via apoptotic mechanisms is an important factor in vascular diseases. c-Jun amino-terminal kinase (JNK) is a member of the mitogen-activated protein kinase family and initiates apoptosis mainly via phosphorylation of the c-Jun transcription factor. We performed this study to clarify the roles of the JNK/c-Jun pathway and apoptosis in the pathogenesis of cerebral aneurysms. METHODS: Cerebral aneurysms from 12 patients and control vessels from 5 patients were studied. We analyzed the expression of phosphorylated JNK and phosphorylated c-Jun in cerebral aneurysms by using immunohistochemical methods. RESULTS: Immunoreactivity for phosphorylated JNK and phosphorylated c-Jun was increased in the vascular walls of the cerebral aneurysms studied. Immunoreactivity for single-stranded deoxyribonucleic acid (a marker of deoxyribonucleic acid damage) was also increased in aneurysmal tissue, compared with control vessels, and was colocalized with that for phosphorylated JNK and phosphorylated c-Jun in smooth muscle cells. CONCLUSION: These observations may lead to better understanding of the role of the JNK/c-Jun pathway in the development of cerebral aneurysms and to new strategies for treatment.

Original languageEnglish (US)
Pages (from-to)997-1004
Number of pages8
JournalNeurosurgery
Volume51
Issue number4
DOIs
StatePublished - Oct 1 2002

Keywords

  • Apoptosis
  • c-Jun
  • c-Jun amino-terminal kinase
  • Cerebral aneurysm
  • Deoxyribonucleic acid fragmentation
  • Vascular remodeling

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

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