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肌醇1,4,5-三磷酸3-激酶和5-磷酸酶活性对Ca2+振荡影响的模拟

Simulations of the effects of inositol 1,4,5-trisphosphate 3-kinase and 5-phosphatase activities on Ca2+ oscillations.

作者信息

Dupont G, Erneux C

机构信息

Unité de Chronobiologie Théorique, Faculté des Sciences, Université Libre de Bruxelles, Belgium.

出版信息

Cell Calcium. 1997 Nov;22(5):321-31. doi: 10.1016/s0143-4160(97)90017-8.

DOI:10.1016/s0143-4160(97)90017-8
PMID:9448939
Abstract

Inositol 1,4,5-trisphosphate (Ins-1,4,5-P3) is responsible for Ca2+ mobilization in response to external stimulation in many cell types. The latter phenomenon often occurs as repetitive Ca2+ spikes. In this study, the effect of the two Ins-1,4,5-P3 metabolizing enzymes (Ins-1,4,5-P3 3-kinase and 5-phosphatase) on the temporal pattern of Ca2+ oscillations has been investigated. On the basis of the well-documented Ins-1,4,5-P3 3-kinase stimulation by the Ca2+/calmodulin complex and of the experimentally-determined kinetic characteristics of these enzymes, we predict that 5-phosphatase primarily controls the levels of Ins-1,4,5-P3 and, thereby, the occurrence and frequency of Ca2+ oscillations. Consequently, the model reproduces the experimental observation performed in Chinese hamster ovary cells that 5-phosphatase overexpression has a much more pronounced effect on the pattern of Ca2+ oscillations than 3-kinase overexpression. We also investigated, in more detail, under which conditions a similar effect could be observed in other cell types expressing various Ins-1,4,5-P3 3-kinase activities.

摘要

肌醇1,4,5 -三磷酸(Ins-1,4,5-P3)在许多细胞类型中负责响应外部刺激而动员Ca2+。后一种现象通常以重复性Ca2+尖峰的形式出现。在本研究中,研究了两种Ins-1,4,5-P3代谢酶(Ins-1,4,5-P3 3-激酶和5-磷酸酶)对Ca2+振荡时间模式的影响。基于Ca2+/钙调蛋白复合物对Ins-1,4,5-P3 3-激酶的充分记录的刺激以及这些酶的实验确定的动力学特征,我们预测5-磷酸酶主要控制Ins-1,4,5-P3的水平,从而控制Ca2+振荡的发生和频率。因此,该模型再现了在中国仓鼠卵巢细胞中进行的实验观察结果,即5-磷酸酶过表达对Ca2+振荡模式的影响比3-激酶过表达更为明显。我们还更详细地研究了在哪些条件下,在表达各种Ins-1,4,5-P3 3-激酶活性的其他细胞类型中可以观察到类似的效果。

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