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人成骨细胞中的环核苷酸磷酸二酯酶(PDEs);PDE抑制对环磷酸腺苷(cAMP)积累的影响。

Cyclic nucleotide phosphodiesterases (PDEs) in human osteoblastic cells; the effect of PDE inhibition on cAMP accumulation.

作者信息

Ahlström Mikael, Pekkinen Minna, Huttunen Minna, Lamberg-Allardt Christel

机构信息

Department of Applied Chemistry and Microbiology, University of Helsinki, P.O. Box 66, 00014 University of Helsinki, Finland.

出版信息

Cell Mol Biol Lett. 2005;10(2):305-19.

Abstract

The regulation of the secondary messengers, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), is crucial in the hormonal regulation of bone metabolism. Both cAMP and cGMP are inactivated by cyclic nucleotide phosphodiesterases (PDEs), a superfamily of enzymes divided into 11 families (PDE1-11). We compared the PDEs of cultured human osteoblasts (NHOst) and SaOS-2 osteosarcoma cells. The PDE activity of NHOst cells consisted of PDE1, PDE3 and PDE7, whereas PDE1, PDE7 and PDE4, but no PDE3 activity was detected in SaOS-2 cells. In line with the difference in the PDE profiles, rolipram, a PDE4 inhibitor, increased the accumulation of cAMP in SaOS-2, but not in NHOst cells. Expression of PDE subtypes PDE1C, PDE3A, PDE4A, PDE4B, PDE7A and PDE7B was detected in both cell types. NHOst cells additionally expressed PDE1A.

摘要

第二信使环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP)的调节在骨代谢的激素调节中至关重要。cAMP和cGMP均被环核苷酸磷酸二酯酶(PDEs)灭活,PDEs是一个分为11个家族(PDE1 - 11)的酶超家族。我们比较了培养的人成骨细胞(NHOst)和SaOS - 2骨肉瘤细胞的PDEs。NHOst细胞的PDE活性由PDE1、PDE3和PDE7组成,而在SaOS - 2细胞中检测到PDE1、PDE7和PDE4,但未检测到PDE3活性。与PDE谱的差异一致,PDE4抑制剂咯利普兰增加了SaOS - 2细胞中cAMP的积累,但在NHOst细胞中未增加。在两种细胞类型中均检测到PDE亚型PDE1C、PDE3A、PDE4A、PDE4B、PDE7A和PDE7B的表达。NHOst细胞还额外表达PDE1A。

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