2-Aminopurine inhibits leptin receptor signal transduction
European Journal of Pharmacology 553 巻 1-3 号
61-66 頁
2006-12-28 発行
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| ファイル情報(添付) | |
| タイトル ( eng ) |
2-Aminopurine inhibits leptin receptor signal transduction
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| 作成者 |
Matsunami Naomi
Nagahama Tomoko
Okuma Yasunobu
Takizawa Tsuyoshi
Nomura Yasuyuki
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| 収録物名 |
European Journal of Pharmacology
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| 巻 | 553 |
| 号 | 1-3 |
| 開始ページ | 61 |
| 終了ページ | 66 |
| 抄録 |
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.
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| 著者キーワード |
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
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| NDC分類 |
医学 [ 490 ]
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| 言語 |
英語
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| 資源タイプ | 学術雑誌論文 |
| 出版者 |
Elsevier
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| 発行日 | 2006-12-28 |
| 権利情報 |
Copyright (c) 2006 Elsevier Ltd.
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| 出版タイプ | Author’s Original（十分な品質であるとして、著者から正式な査読に提出される版） |
| アクセス権 | オープンアクセス |
| 収録物識別子 |
[ISSN] 0014-2999
[DOI] 10.1016/j.ejphar.2006.09.044
[NCID] AA00639687
[PMID] 17070518
[DOI] http://dx.doi.org/10.1016/j.ejphar.2006.09.044
～の異版である
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