國家衛生研究院 NHRI:Item 3990099045/8334

NHRI > Institute of Biotechnology and Pharmaceutical Research > Shiu-Hwa Yeh > Periodical Articles > Item 3990099045/8334

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/8334

Title:	Morphine drives internal ribosome entry site-mediated hnRNP K translation in neurons through opioid receptor-dependent signaling
Authors:	Lee, PT;Chao, PK;Ou, LC;Chuang, JY;Lin, YC;Chen, SC;Chang, HF;Law, PY;Loh, HH;Chao, YS;Su, TP;Yeh, SH
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	Heterogeneous nuclear ribonucleoprotein K (hnRNP K) binds to the promoter region of mu-opioid receptor (MOR) to regulate its transcriptional activity. How hnRNP K contributes to the analgesic effects of morphine, however, is largely unknown. We provide evidence that morphine increases hnRNP K protein expression via MOR activation in rat primary cortical neurons and HEK-293 cells expressing MORs, without increasing mRNA levels. Using the bicistronic reporter assay, we examined whether morphine-mediated accumulation of hnRNP K resulted from translational control. We identified potential internal ribosome entry site elements located in the 5' untranslated regions of hnRNP K transcripts that were regulated by morphine. This finding suggests that internal translation contributes to the morphine-induced accumulation of hnRNP K protein in regions of the central nervous system correlated with nociceptive and antinociceptive modulatory systems in mice. Finally, we found that down-regulation of hnRNP K mediated by siRNA attenuated morphine-induced hyperpolarization of membrane potential in AtT20 cells. Silencing hnRNP K expression in the spinal cord increased nociceptive sensitivity in wild-type mice, but not in MOR-knockout mice. Thus, our findings identify the role of translational control of hnRNP K in morphine-induced analgesia through activation of MOR.
Date:	2014-12-01
Relation:	Nucleic Acids Research. 2014 Dec 1;42(21):13012-13025.
Link to:	http://dx.doi.org/10.1093/nar/gku1016
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0305-1048&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000347914600012
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84945236727
Appears in Collections:	[Shiu-Hwa Yeh] Periodical Articles [Yu-Sheng Chao(2002-2013)] Periodical Articles

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