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

Neurosurgery. 2002 Oct;51(4):997-1002; discussion 1002-4. doi: 10.1097/00006123-200210000-00027.


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.

MeSH terms

  • Adult
  • Aged
  • Apoptosis / physiology
  • Blood Vessels / physiology
  • Cerebrovascular Circulation / physiology
  • DNA, Single-Stranded / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Intracranial Aneurysm / metabolism*
  • JNK Mitogen-Activated Protein Kinases
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinases / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-jun / metabolism


  • DNA, Single-Stranded
  • Proto-Oncogene Proteins c-jun
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases