Cross Talking Calcium, IP3 and Buffer Dynamics Alters ATP and NADH Level in Obese and Normal Hepatocyte Cell.

The cross talk between calcium (Ca2+), IP3 and buffer dynamics regulate various mechanisms in hepatocyte cells. The study of independent systems of calcium, IP3, and buffer signaling provides limited information about cell dynamics. In the current study, coupled reaction-diffusion equations are used to design a cross-talk model for IP3, buffer, and calcium dynamics in a hepatocyte cell. The one-way feedback of calcium, buffer, and IP3 in ATP production, ATP degradation, and NADH production rate is incorporated into the model. Numerical simulation has been done using the Finite Element Method (FEM) along the spatial direction and the Crank-Nicolson (C-N) method along the temporal direction. The numerical results are analysed to determine the effects of alterations in processes of cross-talking dynamics of IP3, buffer, and calcium on ATP and NADH production and degradation rate of ATP in a hepatocyte cell under normal and obesity conditions. The comparative analysis of these findings unveils notable distinctions induced by obesity in calcium dynamics, ATP and NADH synthesis, and ATP degradation kinetics.

Numerical simulation of calcium dynamics dependent ATP degradation, IP3 and NADH production due to obesity in a hepatocyte cell.

Calcium (Ca[Formula: see text]) signals have a crucial role in regulating various processes of almost every cell to maintain its structure and function. Calcium dynamics has been studied in various cells including hepatocytes by many researchers, but the mechanisms of calcium signals involved in regulation and dysregulation of various processes like ATP degradation rate, IP[Formula: see text] and NADH production rate respectively in normal and obese cells are still poorly understood. In this paper, a reaction diffusion equation of calcium is employed to propose a model of calcium dynamics by coupling ATP degradation rate, IP[Formula: see text] and NADH production rate in hepatocyte cells under normal and obese conditions. The processes like source influx, buffer, endoplasmic reticulum (ER), mitochondrial calcium uniporters (MCU) and Na[Formula: see text]/Ca[Formula: see text] exchanger (NCX) have been incorporated in the model. Linear finite element method is used along spatial dimension, and Crank-Nicolson method is used along temporal dimension for numerical simulation. The results have been obtained for the normal hepatocyte cells and for cells due to obesity. The comparative study of these results reveal significant difference caused due to obesity in Ca[Formula: see text] dynamics as well as in ATP degradation rate, IP[Formula: see text] and NADH production rate.

Spatio temporal interdependent calcium and buffer dynamics regulating DAG in a hepatocyte cell due to obesity.

Calcium ions (Ca2+) serve as a crucial signaling mechanism in almost all cells. The buffers are proteins that bind free Ca2+ to reduce the cell's Ca2+ concentration. The most studies reported in the past on calcium signaling in various cells have considered the buffer concentration as constant in the cell. However, buffers also diffuse and their concentration varies dynamically in the cells. Almost no work has been reported on interdependent calcium and buffer dynamics in the cells. In the present study, a model is proposed for inter-dependent spatio-temporal dynamics of calcium and buffer by coupling reaction-diffusion equations of Ca2+ and buffer in a hepatocyte cell. Boundary and initial conditions are framed based on the physiological state of the cell. The effect of various parameters viz. inositol 1,4,5-triphosphate receptor (IP3R), diffusion coefficient, SERCA pump and ryanodine receptor (RyR) on spatio-temporal dynamics of calcium and buffer regulating diacylglycerol (DAG) in a normal and obese hepatocyte cell has been studied using finite element simulation. From the results, it is concluded that the dynamics of calcium and buffer impact each other significantly along the spatio-temporal dimensions, thereby affecting the regulation of all the processes including DAG in a hepatocyte cell. The proposed model is more realistic than the existing ones, as the interdependent system dynamics of calcium and buffer have different regulatory impacts as compared to the individual and independent dynamics of these signaling processes in a hepatocyte cell.