Long chain polyunsaturated fatty acids alter oxytocin signaling and receptor density in cultured pregnant human myometrial smooth muscle cells.
Long chain polyunsaturated fatty acids alter oxytocin signaling and receptor density in cultured pregnant human myometrial smooth muscle cells.
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长链多不饱和脂肪酸会改变培养的孕妇肌层平滑肌细胞中的催产素信号和受体密度。
DOI：
10.1371/journal.pone.0041708
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Allen KG
中科院分区：
文献类型：
--
作者：
Kim PY;Zhong M;Kim YS;Sanborn BM;Allen KG
流行病学研究和干预性临床试验表明，摄入长链n-3多不饱和脂肪酸(LCn-3 PUFA)，如二十二碳六烯酸(DHA)，可延长妊娠时间。尽管其作用机制尚不清楚，但已知2系列前列腺素(PG)在产程的启动和进展中发挥作用。在动物研究中，适度的DHA供应已被证明可以降低胎盘和子宫中前列腺素E_2和前列腺素F_2的α，基质金属蛋白酶-2和基质金属蛋白酶-9的表达，以及胎盘胶原酶的活性。然而，对PG生物合成的调节可能不能解释LC n-3多不饱和脂肪酸在分娩中的所有影响。我们利用培养的人子宫肌层平滑肌细胞研究了LC PUFA作用的一种潜在的PG非依赖性机制。我们的目标是描述LC PUFA治疗对催产素信号的影响，催产素是一种与分娩相关的强大的子宫紧张素。在培养液中加入10~100µM的DHA或花生四烯酸(AA)48h后，这些脂肪酸在膜脂中的积累呈剂量依赖关系。与牛血清白蛋白对照和等摩尔油酸相比，DHA和AA显著抑制催产素刺激下的磷脂酰肌醇转换和[Ca+]i动员。DHA和AA显著降低催产素受体膜浓度，但不改变结合亲和力或受体内化率。这些发现证明了LC n-3多不饱和脂肪酸在催产素信号调节中的作用，并为有关食用鱼类和鱼油延长妊娠的报道提供了新的见解。
Epidemiological studies and interventional clinical trials indicate that consumption of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) such as docosahexaenoic acid (DHA) lengthen gestational duration. Although the mechanisms are not well understood, prostaglandins (PG) of the 2-series are known to play a role in the initiation and progress of labor. In animal studies, modest DHA provision has been shown to reduce placental and uterine PGE2 and PGF2α, matrix metalloproteinase (MMP)-2 and MMP-9 expression, and placental collagenase activity. However, modulation of PG biosynthesis may not account for all the effects of LC n-3 PUFAs in labor. We investigated one potential PG-independent mechanism of LC PUFA action using cultured pregnant human myometrial smooth muscle cells. Our goal was to characterize the effect of LC PUFA treatment on oxytocin signaling, a potent uterotonic hormone involved in labor. The addition of 10 µM–100 µM DHA or arachidonic acid (AA) to the culture media for 48 h resulted in dose dependent enrichment of these fatty acids in membrane lipid. DHA and AA significantly inhibited phosphatidylinositol turnover and [Ca2+]i mobilization with oxytocin stimulation compared to bovine serum albumin control and equimolar oleic acid. DHA and AA significantly reduced oxytocin receptor membrane concentration without altering binding affinity or rate of receptor internalization. These findings demonstrate a role for LC n-3 PUFAs in regulation of oxytocin signaling and provide new insight into additional mechanisms pertaining to reports of dietary fish and fish oil consumption prolonging gestation.
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影响因子：
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