Adiponectin activates endothelial nitric oxide synthase through AMPK signaling after subarachnoid hemorrhage.
Adiponectin is produced from fatty tissue and has been reported to be involved with metabolic syndrome. Recently, adiponectin has been demonstrated to play a neuroprotective role against cerebral ischemia. In this study, we explored the time-course serial expression changes of adiponectin in cerebrospinal fluid (CSF) after subarachnoid hemorrhage (SAH) and the effects of adiponectin on cerebral arteries. The concentrations of adiponectin were measured serially until day 14 in CSF of 8 patients with SAH. The CSF samples obtained from 6 patients suffering from an unruptured aneurysm were used as controls. Serum samples were collected from 6 healthy adult volunteers. Rat cerebral arteries were incubated with adiponectin (2μg/ml). Western blot analysis using AMP-activated protein kinase α (AMPKα), phosphorylated (p)-AMPKα at Thr(172), endothelial nitric oxide synthase (eNOS), p-eNOS at Ser(1177) and actin antibodies was then performed. The adiponectin concentrations in serum and control CSF were 17,670±3748ng/ml and 9.2±3.0ng/ml, respectively. After SAH, the concentration of adiponectin in the CSF significantly increased on the first post-SAH day and gradually decreased thereafter. Adiponectin significantly phosphorylated both the AMPKα and eNOS of the cerebral arteries. Our findings suggest that adiponectin is significantly increased in the CSF after SAH, resulting in the activation of AMPKα and eNOS. Adiponectin plays an important role against cerebral vasospasm via the AMPK/eNOS signaling pathway.
Department of Neurological Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, gun 480-1195, Japan.
Koji
K
Osuka
Yasuo
Y
Watanabe
Muneyoshi
M
Yasuda
Masakazu
M
Takayasu
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D052242:Adiponectin / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid / Q000378:metabolism*
D052242:Adiponectin; D052250:Nitric Oxide Synthase Type III; D055372:AMP-Activated Protein Kinases