- 作者：Hongjun Zhu ; Hegui Wang ; Xiwen Zhang ; Xiaofeng Hou ; Kejiang Cao ; Jiangang Zou ; jgzou@njmu.edu.cn
- 关键词：adherence junction ; N-cadherin ; gap junction ; ventricular tachyarrhythmia ; recombinant mouse ami-nopeptidase N
- 刊名：Journal of Biomedical Research
- 出版年：2010
- 出版时间：July 2010
- 年：2010
- 卷：24
- 期：4
- 页码：292-300
- 全文大小：1154 K
Objective
To evaluate the arrhythmogenic effects of dismantling cadherin-mediated adhesion by recombinant mouse aminopeptidase N (rmAPN) in murine hearts.Methods
rmAPN was incubated with cultured neonatal rat cardiomyocytes as well as being infused in adult mice. The cell-cell connections were immunolabelled and observed by laser confocal microscopy. Disruption of the N-terminal of N-cadherin (N-cad) was detected by western blot and quantitative immunofluorescence. The risk of inducible ventricular tachyarrhythmia was evaluated in mice by an electrophysiological study.
Results
Disrupted cell-cell contact was observed in cultured neonatal rat cardiomyocytes in response to 30-40 ng/¦ÌL rmAPN. Loss of the N-terminal in N-cad and altered distribution of connexin 43 (Cx43) were observed in hearts from rmAPN-infused mice. In addition, a reduction of phosphorylated Cx43 was also detected concomitant with redistribution of Cx43. Electrophysiological studies of rmAPN-infused mice showed prolonged QRS duration and increased inducibility of ventricular tachycardias.
Conclusion
Disruption of N-cad by rmAPN contributes to gap junction remodeling and may elicit arrhythmogenic effects. The disorder of adherent junctions by proteolytic enzymes may play an important role in arrhythmogenic mechanisms in correlated diseases.