Morphine promotes Jurkat cell apoptosis through pro-apoptotic FADD/P53 and anti-apoptotic PI3K/Akt/NF-κB pathways

Deling Yin, Michael Woodruff, Ying Zhang, Sarah Whaley, Junying Miao, Kenneth Ferslew, Jing Zhao, Charles Stuart

Research output: Contribution to journalArticle

Abstract

Opiates have been shown to inhibit cell growth and trigger apoptosis, but the underlying molecular mechanisms remain unclear. We have previously shown that morphine induces Fas expression and promotes Fas-mediated apoptosis. Here, we investigated the mechanisms by which morphine modulates apoptosis in human Jurkat cells. Morphine-induced apoptosis was inhibited by transfection with a dominant negative Fas-associated death domain (FADD) plasmid, revealing that morphine-induced apoptosis is dependent on FADD. Furthermore, suppression of endogenous p53 expression by RNA interference technology considerably attenuated the morphine-induced apoptosis. In addition, morphine-induced apoptosis seems to be dependent on the activation of phosphatidylinositol 3-kinase (PI3K), as PI3K inhibition by the PI3K inhibitor LY294002 significantly enhanced morphine-induced apoptosis. Moreover, inhibition of Akt or nuclear factor-kappaB (NF-κB) expression by RNA interference technology also dramatically increased morphine-induced apoptosis. Our study thus demonstrates that morphine induces Jurkat cell apoptosis through FADD/p53, anti-apoptotic PI3K/Akt and NF-κB pathways.

Original languageEnglish (US)
Pages (from-to)101-107
Number of pages7
JournalJournal of Neuroimmunology
Volume174
Issue number1-2
DOIs
StatePublished - May 1 2006

Keywords

  • Akt
  • Apoptosis
  • FADD
  • Jurkat
  • Morphine
  • NF-κB
  • PI3K
  • p53

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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