TY - JOUR

T1 - A mathematical model linking Ca2+-dependent signaling pathway and gene expression regulation in Human Skeletal Muscle

AU - Akberdin, I. R.

AU - Vertyshev, A. Yu

AU - Pintus, S. S.

AU - Popov, D. V.

AU - Kolpakov, F. A.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - The physiological adaptation to aerobic endurance exercises is provided by activation of signaling pathways in skeletal muscle cells. Training-induced activation of specific signaling pathways results in significant transcriptional responses. Despite the ongoing endeavours to experimentally investigate regulatory mechanisms and signal transduction pathways involved in the contraction-induced adaptation, quantitative contribution of certain signal molecules in expression regulation of genes responsible for intracellular response has not been studied comprehensively yet. The paper presents novel developed model linking Ca2+-dependent signaling pathway and downstream transcription regulation of early and late response genes in human skeletal muscle during exercise. Numerical analysis of the model enabled to reveal crucial steps in this signal transduction pathway for the adaptation and demonstrated the necessity of consideration of additional transcription factors regulating transcription of late response genes in order to adequately reproduce gene expression data that were taken in human vastus lateralis muscle during and after acute cycling exercise.

AB - The physiological adaptation to aerobic endurance exercises is provided by activation of signaling pathways in skeletal muscle cells. Training-induced activation of specific signaling pathways results in significant transcriptional responses. Despite the ongoing endeavours to experimentally investigate regulatory mechanisms and signal transduction pathways involved in the contraction-induced adaptation, quantitative contribution of certain signal molecules in expression regulation of genes responsible for intracellular response has not been studied comprehensively yet. The paper presents novel developed model linking Ca2+-dependent signaling pathway and downstream transcription regulation of early and late response genes in human skeletal muscle during exercise. Numerical analysis of the model enabled to reveal crucial steps in this signal transduction pathway for the adaptation and demonstrated the necessity of consideration of additional transcription factors regulating transcription of late response genes in order to adequately reproduce gene expression data that were taken in human vastus lateralis muscle during and after acute cycling exercise.

KW - BioUML

KW - Ca-dependent signaling pathway

KW - Mathematical model

KW - Physical exercise

KW - Regulation of expression

KW - RNA sequencing

KW - Skeletal muscle

KW - Transcriptome

UR - http://www.scopus.com/inward/record.url?scp=85081684383&partnerID=8YFLogxK

U2 - 10.17537/2020.15.20

DO - 10.17537/2020.15.20

M3 - Article

AN - SCOPUS:85081684383

VL - 15

SP - 20

EP - 39

JO - Mathematical Biology and Bioinformatics

JF - Mathematical Biology and Bioinformatics

SN - 1994-6538

IS - 1

ER -