Morphine promotes Jurkat cell apoptosis through pro-apoptotic FADD/P53 and anti-apoptotic PI3K/Akt/NF-kappaB pathways.
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.
Yin
Deling
D
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
Woodruff
Michael
M
Zhang
Ying
Y
Whaley
Sarah
S
Miao
Junying
J
Ferslew
Kenneth
K
Zhao
Jing
J
Stuart
Charles
C
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
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