Dual mechanisms of Bcl-2 regulation in IP_(3)-receptor-mediated Ca^(2+)release:A computational study  

作　　者：Hong Qi Zhi-Qiang Shi Zhi-Chao Li Chang-Jun Sun Shi-Miao Wang Xiang Li Jian-Wei Shuai 祁宏;史志强);李智超;孙长君;王世苗;李翔;帅建伟(Complex Systems Research Center,Shanxi University,Taiyuan 030006,China;Shanxi Key Laboratory of Mathematical Techniques and Big Data Analysis on Disease Control and Prevention,Shanxi University,Taiyuan 030006,China;School of Mathematical Sciences,Shanxi University,Taiyuan 030006,China;Department of Physics and Fujian Provincial Key Laboratory for Soft Functional Materials Research,Xiamen University,Xiamen 361005,China;State Key Laboratory of Cellular Stress Biology,Innovation Center for Cell Signaling Network,and National Institute for Data Science in Health and Medicine,Xiamen University,Xiamen 361005,China)

机构地区：[1]Complex Systems Research Center,Shanxi University,Taiyuan 030006,China [2]Shanxi Key Laboratory of Mathematical Techniques and Big Data Analysis on Disease Control and Prevention,Shanxi University,Taiyuan 030006,China [3]School of Mathematical Sciences,Shanxi University,Taiyuan 030006,China [4]Department of Physics and Fujian Provincial Key Laboratory for Soft Functional Materials Research,Xiamen University,Xiamen 361005,China [5]State Key Laboratory of Cellular Stress Biology,Innovation Center for Cell Signaling Network,and National Institute for Data Science in Health and Medicine,Xiamen University,Xiamen 361005,China

出　　处：《Chinese Physics B》2021年第10期689-697,共9页中国物理B（英文版）

基　　金：supported by Shanxi Province Science Foundation for Youths(Grant No.201901D211159);the National Natural Science Foundation of China(Grant Nos.11504214,11874310,and 12090052).

摘　　要：Inositol 1,4,5-trisphosphate receptors(IP_(3)R)-mediated calcium ion(Ca^(2+))release plays a central role in the regulation of cell survival and death.Bcl-2 limits the Ca^(2+)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 mechanisms into a set of ordinary differential equations.We firstly simulate the time evolution of Ca^(2+)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 Ca^(2+)signal from a global point of view both in the direct and indirect mechanism models.We then use mathematical analysis to clarify that the indirect mechanism is more efficient than the direct mechanism in repressing Ca^(2+)signal.Lastly,we predict that the two mechanisms restrict Ca^(2+)signal synergistically.Together,our study provides theoretical insights into Bcl-2 regulation in IP_(3)R-mediated Ca^(2+)release,which may be instrumental for the successful development of therapies to target Bcl-2 for cancer treatment.

关 键 词：CA^(2+) BCL-2 bifurcation analysis OSCILLATIONS 

分 类 号：R730.5[医药卫生—肿瘤]