title: Induction of manganese-superoxide dismutase by YS 51, a synthetic 1-(beta-naphtylmethyl)6,7-dihydroxy- 1,2,3,4-tetrahydroisoquinoline alkaloid: implication for anti-inflammatory actions.
abstract: The effect of YS 51, a synthetic 1-(beta-naphtylmethyl)6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline alkaloid, on the expression of manganese-superoxide dismutase (Mn-SOD), an antioxidant enzyme, was examined in sheep pulmonary artery endothelial cells (SPAEC) and a human cervical carcinoma cell line (Hela). YS 51 alone or in combination with cytokines enhanced the expression of Mn-SOD mRNA in SPAEC and Hela cells. YS 51 also showed synergistic effects on the induction of Mn-SOD mRNA with phorbol-12-myristate-13-acetate (TPA) and/or tumor necrosis factor-alpha (TNF-alpha). In Hela cells, the induction of Mn-SOD mRNA by YS 51 was in a time- and dose-dependent manner and the expression of Mn-SOD mRNA was increased to a maximum of 4-fold in 9 h. Enhancement of Mn-SOD mRNA by YS 51 was completely abolished by actinomycin D but not cycloheximide, suggesting that the induction of Mn-SOD mRNA byYS 51 is independent of new protein synthesis. Pretreatment of curcumin, an inhibitor of c-jun N-terminal kinase (JNK), dose-dependently suppressed the induction of Mn-SOD mRNA by YS 51, but not by 2'-amino-3'-methoxyflavone (PD98059) and 4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)imidazol (SB203580), inhibitors of mitogen-activated protein kinase. Also, YS 51 induced the phosphorylation activity of JNK in a time-dependent manner without affecting the phosphorylation activity of the extracellular signal-regulated kinase 1 (ERK1) and p38 MAP kinase. These results implicated that the JNK pathway appears to play a crucial role in mediating the YS 51-induced Mn-SOD gene expression, and that up-regulation of Mn-SOD would contribute to the anti-inflammatory actions mediated by YS 51.
authors.affiliation: Department of Pharmacology, Gyeongsang Institute of Health Science, College of Medicine, Gyeongsang National University, Chinju, Korea.
authors.forename: Han Geuk
authors.initials: HG
authors.lastname: Seo
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Young Shin
authors.initials: YS
authors.lastname: Ko
authors.forename: Hyang Sam
authors.initials: HS
authors.lastname: Pyo
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Kang
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Lee
authors.forename: Min Kyu
authors.initials: MK
authors.lastname: Park
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Yun-Choi
authors.forename: Ki Churl
authors.initials: KC
authors.lastname: Chang
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D003474:Curcumin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004790:Enzyme Induction / Q000187:drug effects* / Q000941:ethics / Q000235:genetics; D005419:Flavonoids / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D008301:Maleimides / Q000494:pharmacology; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012756:Sheep; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism
chemical_list: C495109:1-(beta-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetra-hydroisoquinoline; D005419:Flavonoids; D007093:Imidazoles; D007211:Indoles; D008301:Maleimides; D010703:Phorbol Esters; D011725:Pyridines; D012333:RNA, Messenger; D044005:Tetrahydroisoquinolines; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; C016658:phorbolol myristate acetate; C032974:12-O-retinoylphorbol-13-acetate; D003513:Cycloheximide; D013482:Superoxide Dismutase; D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D003474:Curcumin; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one