TAILIEUCHUNG - Báo cáo khoa học: Regulation of ERK1/2 phosphorylation by acute and chronic morphine – implications for the role of cAMP-responsive element binding factor (CREB)-dependent and Ets-like protein-1 (Elk-1)-dependent transcription; small interfering RNA-based strategy

Extracellular signal-regulated kinases (ERKs) have been shown to be acti-vated by opioids and functionally linked to addiction. Morphine-associated changes in ERK activity seem to be the characteristic features of opioid action. In this study, we observed a rapid and severe increase in ERK1⁄2 activity after a 5 min morphine treatment of HEK-MOR cells (transfected with the ratl-opioid receptor MOR1) expressing l-opioid receptor. | Regulation of ERK1 2 phosphorylation by acute and chronic morphine - implications for the role of cAMP-responsive element binding factor CREB -dependent and Ets-like protein-1 Elk-1 -dependent transcription small interfering RNA-based strategy Agnieszka Ligeza Agnieszka Wawrzczak-Bargiela Dorota Kaminska Michal Korostynski and Ryszard Przewlocki Department of Molecular Neuropharmacology Institute of Pharmacology Polish Academy of Sciences Krakow Poland Keywords ERK opioids protein kinases protein phosphatases RNA interference Correspondence R. Przewlocki Department of Molecular Neuropharmacology Institute of Pharmacology Polish Academy of Sciences 12 Smetna Street 31-343 Krakow Poland Fax 48 12 637 4500 Tel 48 12 662 3218 E-mail nfprzewl@ Received 11 March 2008 revised 23 May 2008 accepted 2 June 2008 doi Extracellular signal-regulated kinases ERKs have been shown to be activated by opioids and functionally linked to addiction. Morphine-associated changes in ERK activity seem to be the characteristic features of opioid action. In this study we observed a rapid and severe increase in ERK1 2 activity after a 5 min morphine treatment of HEK-MOR cells transfected with the rat p-opioid receptor MOR1 expressing p-opioid receptor. Cellular adaptations to chronic 72 h morphine treatment were manifested by a slight and sustained increase in ERK1 2 activity. Withdrawal caused by an opioid receptor antagonist - naloxone - attenuated phosphorylation of ERK1 2. Little information is available on the precise mechanism of ERK activity regulation. Using RNA interference technology we generated stably transfected cells with silenced expression of cAMP-responsive element binding factor CREB and Ets-like protein-1 Elk-1 transcription factors which are known targets for activated ERK1 2. In these cells ERK1 2 activity regulation was altered. Silencing of CREB or Elk-1 significantly increased ERK activation observed after 5 min of morphine

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