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心肌细胞中钙和肌醇1,4,5-三磷酸动力学的三维耦合反应-扩散建模

Three dimensional coupled reaction-diffusion modeling of calcium and inositol 1,4,5-trisphosphate dynamics in cardiomyocytes.

作者信息

Singh Nisha, Adlakha Neeru

机构信息

Applied Mathematics and Humanities Department, SVNIT Ichchhanath Surat Gujarat 395007 India

出版信息

RSC Adv. 2019 Dec 20;9(72):42459-42469. doi: 10.1039/c9ra06929a. eCollection 2019 Dec 18.

DOI:10.1039/c9ra06929a
PMID:35542883
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9076935/
Abstract

Nanoparticles have shown great promise in improving cancer treatment efficacy by changing the intracellular calcium level through activation of intracellular mechanisms. One of the mechanisms of the killing of the cancerous cell by a nanoparticle is through elevation of the intracellular calcium level. Evidence accumulated over the past decade indicates a pivotal role for the IP receptor mediated Ca release in the regulation of the cytosolic and the nuclear Ca signals. There have been various studies done suggesting the role of IP receptors (IPR) and IP production and degradation in cardiomyocytes. In the present work, we have proposed a three-dimensional unsteady-state mathematical model to describe the mechanism of cardiomyocytes which focuses on evaluation of various parameters that affect these coupled dynamics and elevate the cytosolic calcium concentration which can be helpful to search for novel therapies to cure these malignancies by targeting the complex calcium signaling process in cardiomyocytes. Our study suggests that there are other factors involved in this signaling which can increase the calcium level, which can help in finding treatment for cancer. The cytosolic calcium level may be controlled by IP signaling, , source influx of calcium () and maximum production of IP ( ). We believe that the proposed model suggests new insight into finding treatment for cancer in cardiomyocytes through elevation of the cytosolic Ca concentration by various parameters like , , and especially by other complex cell signaling dynamics, namely IP dynamics.

摘要

纳米颗粒已显示出通过激活细胞内机制改变细胞内钙水平来提高癌症治疗效果的巨大潜力。纳米颗粒杀死癌细胞的机制之一是通过提高细胞内钙水平。过去十年积累的证据表明,IP受体介导的钙释放 在调节细胞质和细胞核钙信号中起关键作用。已经有各种研究表明IP受体(IPR)以及IP在心肌细胞中的产生和降解的作用。在本工作中,我们提出了一个三维非稳态数学模型来描述心肌细胞的机制,该模型侧重于评估影响这些耦合动力学并提高细胞质钙浓度的各种参数,这有助于通过靶向心肌细胞中复杂的钙信号过程来寻找治疗这些恶性肿瘤的新疗法。我们的研究表明,该信号传导中还涉及其他可增加钙水平的因素,这有助于找到癌症治疗方法。细胞质钙水平可能受IP信号传导、钙的源流入( )和IP的最大产生量( )控制。我们相信,所提出的模型通过诸如 、 、 等各种参数,特别是通过其他复杂的细胞信号动力学,即IP动力学,提高细胞质钙浓度,为在心肌细胞中寻找癌症治疗方法提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/da3ab5a28084/c9ra06929a-f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/991396e87051/c9ra06929a-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/648b9cc8baa9/c9ra06929a-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/c689d53ce0c5/c9ra06929a-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/7dea9e172ca9/c9ra06929a-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/5318a4905ca3/c9ra06929a-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/3a2fd081761c/c9ra06929a-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/e48a660ca511/c9ra06929a-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/7195d0cd56ba/c9ra06929a-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/da3ab5a28084/c9ra06929a-f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/991396e87051/c9ra06929a-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/f81cfeba87b2/c9ra06929a-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/648b9cc8baa9/c9ra06929a-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/c689d53ce0c5/c9ra06929a-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/7dea9e172ca9/c9ra06929a-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/5318a4905ca3/c9ra06929a-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/3a2fd081761c/c9ra06929a-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/e48a660ca511/c9ra06929a-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/7195d0cd56ba/c9ra06929a-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcf/9076935/da3ab5a28084/c9ra06929a-f10.jpg

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