Karube-Harada A, Sugino N, Kashida S, Takiguchi S, Takayama H, Yamagata Y, Nakamura Y, Kato H
Department of Obstetrics and Gynecology, Yamaguchi University School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan.
Mol Hum Reprod. 2001 Nov;7(11):1065-72. doi: 10.1093/molehr/7.11.1065.
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.
本研究旨在探讨肿瘤坏死因子-α（TNFα）对人子宫内膜基质细胞（ESC）中超氧化物歧化酶（SOD）表达的影响，并确定ESC与蜕膜化ESC对TNFα的反应性是否存在差异。TNFα以剂量依赖的方式增加ESC中锰超氧化物歧化酶（Mn-SOD）的mRNA水平和Mn-SOD活性。蜕膜化ESC产生效应所需的TNFα浓度低于未蜕膜化的ESC。TNFα对两种类型细胞中的铜锌超氧化物歧化酶（Cu,Zn-SOD）表达均无影响。用RNA合成抑制剂放线菌素D孵育ESC可阻断TNFα诱导的Mn-SOD mRNA表达，但蛋白质合成抑制剂环己酰亚胺则无此作用。蛋白激酶C（PKC）抑制剂H7也抑制两种类型细胞中TNFα刺激的Mn-SOD mRNA表达。这些发现表明，TNFα诱导的Mn-SOD表达在转录水平受到调控，并由PKC依赖性磷酸化介导，且TNFα发挥作用不需要新的蛋白质合成。总之，TNFα诱导人ESC中Mn-SOD表达。这种现象可能对保护ESC免受细胞因子介导的氧化应激很重要。
