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首页> 外文期刊>The Biochemical Journal >A metabolic reaction-diffusion model for PKC alpha translocation via PIP2 hydrolysis in an endothelial cell
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A metabolic reaction-diffusion model for PKC alpha translocation via PIP2 hydrolysis in an endothelial cell

机译：A metabolic reaction-diffusion model for PKC alpha translocation via PIP2 hydrolysis in an endothelial cell

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摘要

Hydrolysis of the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) at the cell membrane induces the release of inositol 1,4,5-trisphosphate (IP3) into the cytoplasm and diffusion of diacylglycerol (DAG) through the membrane, respectively. Release of IP3 subsequently increases Ca2+ levels in the cytoplasm, which results in activation of protein kinase C alpha (PKC alpha) by Ca2+ and DAG, and finally the translocation of PKC alpha from the cytoplasm to the membrane. In this study, we developed a metabolic reaction-diffusion framework to simulate PKC alpha translocation via PIP2 hydrolysis in an endothelial cell. A three-dimensional cell model, divided into membrane and cytoplasm domains, was reconstructed from confocal microscopy images. The associated metabolic reactions were divided into their corresponding domain; PIP2 hydrolysis at the membrane domain resulted in DAG diffusion at the membrane domain and IP3 release into the cytoplasm domain. In the cytoplasm domain, Ca2+ was released from the endoplasmic reticulum, and IP3, Ca2+, and PKCa diffused through the cytoplasm. PKC alpha bound Ca2+ at, and diffused through, the cytoplasm, and was finally activated by binding with DAG at the membrane. Using our model, we analyzed IP3 and DAG dynamics, Ca2+ waves, and PKC alpha translocation in response to a microscopic stimulus. We found a qualitative agreement between our simulation results and our experimental results obtained by live-cell imaging. Interestingly, our results suggest that PKC alpha translocation is dominated by DAG dynamics. This three-dimensional reaction-diffusion mathematical framework could be used to investigate the link between PKC alpha activation in a cell and cell function.

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