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妊娠对人子宫肌层中磷酸二酯酶4(PDE4)环磷酸腺苷特异性磷酸二酯酶信使核糖核酸表达的影响。

Effect of pregnancy on PDE4 cAMP-specific phosphodiesterase messenger ribonucleic acid expression in human myometrium.

作者信息

Leroy M J, Méhats C, Duc-Goiran P, Tanguy G, Robert B, Dallot E, Mignot T M, Grangé G, Ferré F

机构信息

Institut National de la Santé et de la Recherche Médicale, Unité U361, Maternité Port-Royal-Cochin, Université René Descartes, Paris, France.

出版信息

Cell Signal. 1999 Jan;11(1):31-7. doi: 10.1016/s0898-6568(98)00028-x.

DOI:10.1016/s0898-6568(98)00028-x
PMID:10206342
Abstract

In light of the important role of the second messengers cAMP and cGMP in the mechanism of relaxation in the human myometrium, specific regulation of the phosphodiesterase (PDE) enzymatic system responsible for cyclic nucleotide inactivation is essential. We previously identified in the human myometrium PDE4 cAMP-specific PDE as by far the most abundant isoform. Here we have studied the expression patterns of mRNAs for the four cloned human PDE4 genes in the myometria of pregnant and non-pregnant women. Concurrent expression of the PDE4A, 4B, 4C and 4D genes is demonstrated. We found that the PDE4D transcripts are the most prominently expressed. PDE4A and PDE4B mRNAs also are markedly abundant, whereas lower expression is observed for PDE4C mRNAs. Interestingly, we showed that transcripts of PDE4B2 are more abundant in the myometria of pregnant women than in non-pregnant women, whereas no difference between the two tissues was detected for PDE4A, 4C and 4D mRNAs. Cultured human myometrial cells, which present a high level of PDE4 activity and express the four PDE4 mRNA subtypes, provide us with an appropriate model to further evaluate whether the level of expression of the PDE 4B2 mRNA subtype is under hormonal regulation.

摘要

鉴于第二信使环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP)在人类子宫肌层舒张机制中发挥的重要作用,对负责环核苷酸失活的磷酸二酯酶(PDE)酶系统进行特异性调节至关重要。我们之前在人类子宫肌层中鉴定出,PDE4(cAMP特异性PDE)是迄今为止最丰富的亚型。在此,我们研究了4种克隆的人类PDE4基因的mRNA在孕妇和非孕妇子宫肌层中的表达模式。结果表明,PDE4A、4B、4C和4D基因同时表达。我们发现,PDE4D转录本表达最为显著。PDE4A和PDE4B的mRNA也明显丰富,而PDE4C的mRNA表达较低。有趣的是,我们发现PDE4B2的转录本在孕妇子宫肌层中比在非孕妇子宫肌层中更丰富,而PDE4A、4C和4D的mRNA在这两种组织中未检测到差异。培养的人类子宫肌层细胞具有高水平的PDE4活性并表达4种PDE4 mRNA亚型,这为我们提供了一个合适的模型,以进一步评估PDE 4B2 mRNA亚型的表达水平是否受激素调节。

相似文献

1
Effect of pregnancy on PDE4 cAMP-specific phosphodiesterase messenger ribonucleic acid expression in human myometrium.妊娠对人子宫肌层中磷酸二酯酶4(PDE4)环磷酸腺苷特异性磷酸二酯酶信使核糖核酸表达的影响。
Cell Signal. 1999 Jan;11(1):31-7. doi: 10.1016/s0898-6568(98)00028-x.
2
Selective up-regulation of phosphodiesterase-4 cyclic adenosine 3',5'-monophosphate (cAMP)-specific phosphodiesterase variants by elevated cAMP content in human myometrial cells in culture.培养的人子宫肌层细胞中,环磷酸腺苷(cAMP)含量升高导致磷酸二酯酶4环腺苷3',5'-单磷酸(cAMP)特异性磷酸二酯酶变体的选择性上调。
Endocrinology. 1999 Jul;140(7):3228-37. doi: 10.1210/endo.140.7.6847.
3
Challenge of human Jurkat T-cells with the adenylate cyclase activator forskolin elicits major changes in cAMP phosphodiesterase (PDE) expression by up-regulating PDE3 and inducing PDE4D1 and PDE4D2 splice variants as well as down-regulating a novel PDE4A splice variant.用腺苷酸环化酶激活剂福斯高林刺激人Jurkat T细胞,通过上调磷酸二酯酶3(PDE3)、诱导磷酸二酯酶4D1(PDE4D1)和磷酸二酯酶4D2(PDE4D2)剪接变体以及下调一种新型磷酸二酯酶4A(PDE4A)剪接变体,引发环磷酸腺苷(cAMP)磷酸二酯酶(PDE)表达的重大变化。
Biochem J. 1997 Jan 1;321 ( Pt 1)(Pt 1):165-75. doi: 10.1042/bj3210165.
4
Pregnancy induces a modulation of the cAMP phosphodiesterase 4-conformers ratio in human myometrium: consequences for the utero-relaxant effect of PDE4-selective inhibitors.妊娠可诱导人子宫肌层中环磷酸腺苷磷酸二酯酶4构象异构体比例的调节:对PDE4选择性抑制剂子宫舒张作用的影响。
J Pharmacol Exp Ther. 2000 Feb;292(2):817-23.
5
Comparison of recombinant human PDE4 isoforms: interaction with substrate and inhibitors.重组人磷酸二酯酶4(PDE4)同工型的比较:与底物和抑制剂的相互作用
Cell Signal. 1998 Jun;10(6):427-40. doi: 10.1016/s0898-6568(97)00169-1.
6
Anti-inflammatory and utero-relaxant effects in human myometrium of new generation phosphodiesterase 4 inhibitors.新一代磷酸二酯酶4抑制剂对人子宫肌层的抗炎及子宫舒张作用
Biol Reprod. 2004 Feb;70(2):458-64. doi: 10.1095/biolreprod.103.023051. Epub 2003 Oct 15.
7
Prolonged beta adrenoceptor stimulation up-regulates cAMP phosphodiesterase activity in human monocytes by increasing mRNA and protein for phosphodiesterases 4A and 4B.长期的β肾上腺素能受体刺激通过增加磷酸二酯酶4A和4B的mRNA和蛋白质,上调人单核细胞中的cAMP磷酸二酯酶活性。
J Pharmacol Exp Ther. 1996 Feb;276(2):810-8.
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Regulation of cAMP-specific phosphodiesterases type 4B and 4D (PDE4) splice variants by cAMP signaling in primary cortical neurons.原代皮层神经元中cAMP信号对4B型和4D型cAMP特异性磷酸二酯酶(PDE4)剪接变体的调控
J Neurochem. 2002 May;81(4):745-57. doi: 10.1046/j.1471-4159.2002.00878.x.
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Splice variants of the cyclic nucleotide phosphodiesterase PDE4D are differentially expressed and regulated in rat tissue.环核苷酸磷酸二酯酶PDE4D的剪接变体在大鼠组织中差异表达并受到调控。
Biochem J. 2005 Jun 15;388(Pt 3):803-11. doi: 10.1042/BJ20050030.
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Differential expression and function of phosphodiesterase 4 (PDE4) subtypes in human primary CD4+ T cells: predominant role of PDE4D.磷酸二酯酶4(PDE4)亚型在人原代CD4 + T细胞中的差异表达及功能:PDE4D的主要作用
J Immunol. 2007 Apr 15;178(8):4820-31. doi: 10.4049/jimmunol.178.8.4820.

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