title: Morphine promotes Jurkat cell apoptosis through pro-apoptotic FADD/P53 and anti-apoptotic PI3K/Akt/NF-kappaB pathways.
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-kappaB) 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-kappaB pathways.
authors.affiliation: Department of Internal Medicine, James Quillen College of Medicine, East Tennessee State University, P.O. Box 70622, Johnson City, TN 37614, United States. yin@mail.etsu.edu
authors.forename: Deling
authors.initials: D
authors.lastname: Yin
authors.forename: Michael
authors.initials: M
authors.lastname: Woodruff
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Sarah
authors.initials: S
authors.lastname: Whaley
authors.forename: Junying
authors.initials: J
authors.lastname: Miao
authors.forename: Kenneth
authors.initials: K
authors.lastname: Ferslew
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Charles
authors.initials: C
authors.lastname: Stuart
mesh_terms: D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D029681:Arabidopsis Proteins / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count / Q000379:methods; D002867:Chromones / Q000494:pharmacology; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D009020:Morphine / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D009294:Narcotics / Q000494:pharmacology*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D034622:RNA Interference / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014162:Transfection / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D029681:Arabidopsis Proteins; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D016328:NF-kappa B; D009294:Narcotics; D016159:Tumor Suppressor Protein p53; D049452:Green Fluorescent Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D009020:Morphine; D044943:Fatty Acid Desaturases; C084083:Fad7 protein, Arabidopsis; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt