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: Han Geuk Seo, Hyo Jung Kim, Young Shin Ko, Hyang Sam Pyo, Young Jin Kang, Young Soo Lee, Min Kyu Park, Hye Sook Yun-Choi, Ki Churl Chang
• Journal: Pharmacology (Pharmacology) Vol. 71 Issue 2 Pg. 57-65 (Jun 2004) ISSN: 0031-7012 [Print] Switzerland
• PMID: 15118344 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2004 S. Karger AG, Basel

Chemical References

• 1-(beta-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetra-hydroisoquinoline
• Flavonoids
• Imidazoles
• Indoles
• Maleimides
• Phorbol Esters
• Pyridines
• RNA, Messenger
• Tetrahydroisoquinolines
• Tumor Necrosis Factor-alpha
• Dactinomycin
• phorbolol myristate acetate
• 12-O-retinoylphorbol-13-acetate
• Cycloheximide
• Superoxide Dismutase
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinase 3
• p38 Mitogen-Activated Protein Kinases
• Curcumin
• bisindolylmaleimide I
• Tetradecanoylphorbol Acetate
• SB 203580
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Animals
• Blotting, Northern
• Curcumin (pharmacology)
• Cycloheximide (pharmacology)
• Dactinomycin (pharmacology)
• Dose-Response Relationship, Drug
• Drug Synergism
• Drug Therapy, Combination
• Endothelial Cells (drug effects, physiology)
• Endothelium, Vascular (cytology, drug effects, physiology)
• Enzyme Induction (drug effects, ethics, genetics)
• Flavonoids (pharmacology)
• Gene Expression Regulation, Enzymologic (drug effects, genetics)
• HeLa Cells
• Humans
• Imidazoles (pharmacology)
• Indoles (pharmacology)
• JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors, drug effects, metabolism)
• Maleimides (pharmacology)
• Mitogen-Activated Protein Kinase 3 (drug effects, metabolism)
• Phorbol Esters (pharmacology)
• Phosphorylation (drug effects)
• Pulmonary Artery (cytology, drug effects, physiology)
• Pyridines (pharmacology)
• RNA, Messenger (genetics, metabolism)
• Sheep
• Superoxide Dismutase (antagonists & inhibitors, genetics, metabolism)
• Tetradecanoylphorbol Acetate (analogs & derivatives, pharmacology)
• Tetrahydroisoquinolines (pharmacology)
• Tumor Necrosis Factor-alpha (pharmacology)
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, drug effects, metabolism)