Tumor necrosis factor alpha stimulates adenylyl cyclase activity in human myometrial cells.
Tumor necrosis factor alpha stimulates adenylyl cyclase activity in human myometrial cells.
复制标题
肿瘤坏死因子 α 刺激人子宫肌细胞中的腺苷酸环化酶活性。
DOI：
10.1095/biolreprod.102.004168
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发表时间：
2003
影响因子：
3.6
通讯作者：
Emala,CharlesW
中科院分区：
文献类型：
--
作者：
Gogarten,Wiebke;Lindeman,KarenS;Hirshman,CarolA;Emala,CharlesW
肿瘤坏死因子 α (TNFα) 等细胞因子与羊水感染以及早产和足月分娩有关。根本机制尚不完全清楚。在一些平滑肌细胞中，TNFα 影响 β-肾上腺素能/腺苷酸环化酶途径的功能。本研究旨在检查慢性 TNFα 暴露对人子宫肌层细胞培养物中腺苷酸环化酶活性的影响。慢性 TNFα 暴露导致基础、GTP、NaF 和毛喉素刺激的腺苷酸环化酶 (AC) 活性呈剂量和时间依赖性增加。通过免疫印迹测定，AC 活性的增加不是由异源三聚体 G 蛋白 Gsα 或 Giα 表达的变化介导的。此外，在吲哚美辛存在的情况下，AC 活性增加，表明这些变化不是由 TNFα 诱导的前列腺素产生变化引起的。目前的结果表明，从子宫下段获得的人子宫肌细胞中，TNFα诱导的AC活性增加发生在G蛋白/AC相互作用水平或AC酶本身水平。
Cytokines such as tumor necrosis factor α (TNFα) have been implicated in amniotic fluid infections and preterm and term labor. The underlying mechanisms are incompletely understood. In some smooth muscle cells, TNFα affects function of the β-adrenergic/adenylyl cyclase pathway. The present study was performed to examine the effects of chronic TNFα exposure on adenylyl cyclase activity in cell cultures of human myometrium. Chronic TNFα exposure led to a dose- and time-dependent increase in basal-, GTP-, NaF-, and forskolin-stimulated adenylyl cyclase (AC) activity. The increase in AC activity was not mediated by changes in the expression of the heterotrimeric G proteins Gsα or Giα as determined by immunoblotting. In addition, increases in AC activity occurred in the presence of indomethacin, indicating that these changes were not provoked by TNFα-induced changes in prostaglandin production. The present results suggest that TNFα-induced increases in AC activity in human myometrial cells obtained from the lower uterine segment occur at the level of G-protein/AC interaction or at the level of the AC enzyme itself.