【摘 要】
:
Inositol 1,4,5-trisphosphate receptors(IP3R)-mediated calcium ion(Ca2+)release plays a central role in the regula-tion of cell survival and death.Bcl-2 limits the Ca2+release function of the IP3R through a direct or indirect mechanism.However,the two mech
【机 构】
:
Complex Systems Research Center,Shanxi University,Taiyuan 030006,China;Shanxi Key Laboratory of Math
论文部分内容阅读
Inositol 1,4,5-trisphosphate receptors(IP3R)-mediated calcium ion(Ca2+)release plays a central role in the regula-tion of cell survival and death.Bcl-2 limits the Ca2+release function of the IP3R through a direct or indirect mechanism.However,the two mechanisms are overwhelmingly complex and not completely understood.Here,we convert the mecha-nisms into a set of ordinary differential equations.We firstly simulate the time evolution of Ca2+concentration under two different levels of Bcl-2 for the direct and indirect mechanism models and compare them with experimental results available in the literature.Secondly,we employ one-and two-parameter bifurcation analysis to demonstrate that Bcl-2 can suppress Ca2+signal from a global point of view both in the direct and indirect mechanism models.We then use mathematical anal-ysis to clarify that the indirect mechanism is more efficient than the direct mechanism in repressing Ca2+signal.Lastly,we predict that the two mechanisms restrict Ca2+signal synergistically.Together,our study provides theoretical insights into Bcl-2 regulation in IP3R-mediated Ca2+release,which may be instrumental for the successful development of therapies to target Bcl-2 for cancer treatment.
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