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ID 17066
file
creator
Matsunami, Naomi
Nagahama, Tomoko
Okuma, Yasunobu
Takizawa, Tsuyoshi
Nomura, Yasuyuki
subject
leptin
2-aminopurine
signal transducer and activator of transcription 3 (STAT3)
extracellular signal-regulated kinase (ERK)
double-strand RNA-activated protein kinase (PKR)
Ob-Rb leptin receptor
NDC
Medical sciences
abstract
Leptin is an important circulating signal for regulation of food intake and body weight. In the present study, we investigated the effect of 2-aminopurine (2-AP), an inhibitor of double-strand RNA-activated protein kinase (PKR), on leptin signal transduction. 2-AP dose-dependently inhibited leptin-induced phosporylation of signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) in HEK293 cells stably transfected with the Ob-Rb leptin receptor. On the other hand, we observed only slight inhibition of leptin-induced STAT3 activation by purine treatment, indicating that the inhibitory effect will be dramatically enhanced in the presence of an amino group. 2-AP did not inhibit PMA-induced ERK activation, indicating that the effect may be leptin-signal specific. The inhibitory effect of 2-AP was not mediated by newly synthesized protein because the inhibitory effect of 2-AP on leptin-induced STAT3 activation was not abrogated in the presence of the protein synthesis inhibitor cycloheximide. Interestingly, leptin did not induce PKR activation, suggesting that the effect of 2-AP on leptin signal may be independent of PKR. Finally, 2-AP inhibited leptin-induced phosphorylation of the Ob-Rb leptin receptor. These results provide evidence of a novel action of 2-AP, i.e., inhibition of activation of leptin signal transduction at the level of the Ob-Rb leptin receptor.
journal title
European Journal of Pharmacology
volume
Volume 553
issue
Issue 1-3
start page
61
end page
66
date of issued
2006-12-28
publisher
Elsevier
issn
0014-2999
ncid
publisher doi
pubmed id
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
author
rights
Copyright (c) 2006 Elsevier Ltd.
relation is version of URL
http://dx.doi.org/10.1016/j.ejphar.2006.09.044
department
Graduate School of Biomedical Science