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.
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.


CONCLUSIONS
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.
Takagi
Yasushi
Y
Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Japan. ytakagi@kuhp.kyoto-u.ac.jp
Ishikawa
Masatsune
M
Nozaki
Kazuhiko
K
Yoshimura
Shinichi
S
Hashimoto
Nobuo
N
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D001808:Blood Vessels / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology; D004277:DNA, Single-Stranded / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002532:Intracranial Aneurysm / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism
D004277:DNA, Single-Stranded; D016755:Proto-Oncogene Proteins c-jun; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases