Mu-opioid receptor-mediated phosphorylation of IkappaB kinase in human neuroblastoma SH-SY5Y cells.
Opioid receptors are involved in regulating neuronal survival. Here we demonstrate that activation of the mu-opioid receptor in human neuroblastoma SH-SY5Y cells led to the phosphorylations of IkappaB kinase (IKK) and p65, denoting the stimulation of the nuclear factor-kappaB (NFkappaB) transcription factor. This response was mediated through pertussis toxin-sensitive G proteins. The mu-opioid-induced IKK phosphorylation required extracellular signal-regulated protein kinase, phosphatidylinositol 3-kinase and c-Src. Moreover, c-Jun N-terminal kinase and calmodulin-dependent kinase II also participated in the IKK activation, despite the lack of involvement of phospholipase Cbeta and protein kinase C. These data suggest that the mu-opioid receptor is capable of simulating NFkappaB signaling via the phosphorylation of IKK and p65 in human neuroblastoma SH-SY5Y cells.
Liu
Andrew M F
AM
Department of Biochemistry, Molecular Neuroscience Center, and Biotechnology Research Institute, Hong Kong University of Science and Technology, Kowloon, SAR, China.
Wong
Yung H
YH
D000701:Analgesics, Opioid / Q000494:pharmacology; D000704:Analysis of Variance; D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000502:physiology*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D019892:eIF-2 Kinase / Q000378:metabolism
D000701:Analgesics, Opioid; D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D009270:Naloxone; D013004:Somatostatin; D037342:Pertussis Toxin; D019892:eIF-2 Kinase; D020928:Mitogen-Activated Protein Kinases