Name
Title | ||
|---|---|---|
Development of a Novel Markov Chain Model for Oxidative-dependent CaMKIIδ Activation. |
Abstract | ||
|---|---|---|
Dysfunction in the Calcium (Ca2+)-calmodulin (CaM) dependent kinase II (CaMKII) signalling can lead to several pathologies, such as heart failure and arrhythmia. Especially, the role of CaMKII signalling in oxidative stress-induced arrhythmias remains unclear. In this study, we aimed to develop a new Markov chain model of CaMKII δ-isoform (CaMKIId) that involves both of the autophosphorylation and oxidation pathways to better simulate CaMKII signalling under oxidative stress in cardiomyocytes. Based on the four-state model developed by Chiba et al., we implemented two oxidized states including a Ca2+/CaM-bound state and a Ca2+/CaM-dissociated state, representing the new pathway of oxidation-dependent activation. Using the model, we reproduced the CaM affinity to CaMKIId, the dependence of autophosphorylation on CaM. The frequency-dependent activation of CaMKII was simulated for both CaMKII ΰ- and δ-isoforms. For the oxidation pathway, our simulation suggested that H2O2 increased the kinase activity in a dose-dependent manner, which also fitted to experimental data. Finally this model was incorporated in a human atrial cell model to simulate the effects of CaMKII activation on cellular action potentials. |
Year | Venue | Field |
|---|---|---|
2015 | CinC | Signalling,Oxidative phosphorylation,Calcium,Internal medicine,Markov chain,Ca2+/calmodulin-dependent protein kinase,Kinase,Cell biology,Chemistry,Autophosphorylation,Oxidative stress,Endocrinology |
DocType | Citations | PageRank |
Conference | 0 | 0.34 |
References | Authors | |
0 | 5 | |
Name | Order | Citations | PageRank |
|---|---|---|---|
| Shanzhuo Zhang | 1 | 7 | 2.45 |
| Qince Li | 2 | 7 | 9.91 |
| Lufang Zhou | 3 | 0 | 0.34 |
| Kuanquan Wang | 4 | 1617 | 141.11 |
| Henggui Zhang | 5 | 105 | 51.88 |