Identification and functional analysis of a new putative caveolin-3 variant found in a patient with sudden unexplained death

Journal of Biomedical Science

Salvatore Amoroso¹  Adriano Tagliabracci¹  Santo Gratteri²  Mauro Pesaresi¹  Federica Alessandrini¹  Annamaria Assunta Nasti¹  Vincenzo Lariccia¹ 

[1] Department of Biomedical Sciences and Public Health, School of Medicine, University “Politecnica delle Marche”, Ancona, Italy;Department of Health Sciences, University “Magna Graecia”, Catanzaro, Italy

关键词: ERKs;    Sudden cardiac death;    Caveolin-3;   

Others  :  1137630
DOI  :  10.1186/1423-0127-21-58

 received in 2014-01-10, accepted in 2014-06-03,  发布年份 2014

【 摘 要 】

Background

Sudden cardiac death (SCD) is the clinical outcome of a lethal arrhythmia that can develop on the background of unrecognized channelopathies or cardiomyopathies. Several susceptibility genes have been identified for the congenital forms of these cardiac diseases, including caveolin-3 (Cav-3) gene. In the heart Cav-3 is the main component of caveolae, plasma membrane domains that regulate multiple cellular processes highly relevant for cardiac excitability, such as trafficking, calcium homeostasis, signal transduction and cellular response to injury. Here we characterized a new putative Cav-3 variant, Cav-3 V82I, found in a patient with SCD.

Results

In heterologous systems Cav-3 V82I was expressed at significantly higher level than Cav-3 WT and accumulated within the cells. Cells expressing Cav-3 V82I exhibited a decreased activation of extracellular-signal-regulated kinases (ERKs) and were more vulnerable to sub-lethal osmotic stress.

Conclusion

Considering that abnormal loss of myocytes can play a mechanistic role in lethal cardiac diseases, we suggest that the detrimental effect of Cav-3 V82I variant on cell viability may participate in determining the susceptibility to cardiac death.

【 授权许可】

   
2014 Lariccia et al.; licensee BioMed Central Ltd.

【 图 表 】

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