title: Effect of c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (p38 MAPK) in morphine-induced tau protein hyperphosphorylation.
abstract: Opioids have been widely used in clinical practice as potent pain relievers for centuries. However, opioids have many deleterious effects. It has been reported that opioid increases tau protein phosphorylation. Hyperphosphorylation of tau is also a pathological feature of Alzheimer's disease and other chronic neurodegenerative disorders. However, the underlying mechanism by which opioids enhance tau phosphorylation is not yet known. In this study, we treated rat embryo cortical neurons with morphine and observed its effect on tau phosphorylation. We found that morphine induced tau hyperphosphorylation and increased levels of phospho-JNK and phospho-p38; these effects were blocked by pretreatment with naloxone. Inhibition of JNK by SP600125 significantly reduced tau hyperphosphorylation in neurons treated with morphine. Similarly, SB203580, an antagonist of p38 MAPK, abolished tau hyperphosphorylation in neurons treated with morphine. Our data suggest that JNK/p38 MAPK, activated by morphine in an opioid receptor-dependent manner, may lead to tau hyperphosphorylation.
authors.affiliation: Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Cao
authors.forename: Funing
authors.initials: F
authors.lastname: Liu
authors.forename: Fengtao
authors.initials: F
authors.lastname: Ji
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liang
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.forename: Tinghuai
authors.initials: T
authors.lastname: Wang
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D000873:Anthracenes; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D016875:tau Proteins; C432165:pyrazolanthrone; D009020:Morphine; D048031:JNK Mitogen-Activated Protein Kinases; D048055:Mitogen-Activated Protein Kinase 8; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580