Induction of manganese superoxide dismutase by tumour necrosis factor-alpha in human endometrial stromal cells.
The present study was undertaken to investigate the effect of tumour necrosis factor-alpha (TNFalpha) on superoxide dismutase (SOD) expression in human endometrial stromal cells (ESC) and to determine whether there is a difference in responsiveness to TNFalpha between ESC and decidualized ESC. TNFalpha increased manganese-SOD (Mn-SOD) mRNA level and Mn-SOD activity in a dose-dependent manner in ESC. The concentration of TNFalpha required for an effect was lower for decidualized ESC than for non-decidualized ESC. TNFalpha had no effect on copper-zinc-SOD (Cu,Zn-SOD) expression in either type of cell. Incubation of ESC with actinomycin D, an RNA synthesis inhibitor, blocked TNFalpha-induced Mn-SOD mRNA expression, but cycloheximide, a protein synthesis inhibitor, had no effect. H7, an inhibitor of protein kinase C (PKC), also inhibited TNFalpha-stimulated Mn-SOD mRNA expression in both types of cells. These findings suggest that TNFalpha-induced Mn-SOD expression is regulated at the transcription level and mediated by PKC-dependent phosphorylation and that de-novo protein synthesis is not required for the TNFalpha effect. In summary, TNFalpha induces Mn-SOD expression in human ESC. This phenomenon may be important for protection of ESC from cytokine-mediated oxidative stress.
Karube-Harada
A
A
Department of Obstetrics and Gynecology, Yamaguchi University School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan.
Sugino
N
N
Kashida
S
S
Takiguchi
S
S
Takayama
H
H
Yamagata
Y
Y
Nakamura
Y
Y
Kato
H
H
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000328:Adult; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation; D004717:Endometrium / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008875:Middle Aged; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D003513:Cycloheximide; D013482:Superoxide Dismutase; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate