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| Autor: | My Vu Diem, Hiep Nguyen Minh, Nam Nguyen Huy, Yen Pham Thi Bach, Bao Bui Chi, Duy Pham Ngoc, Nga Nguyen Thi Huynh |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Pathology
medicine.medical_specialty biology business.industry Desmoplakin Cardiac muscle Cancer Connexin medicine.disease Cell junction General Biochemistry Genetics and Molecular Biology Sudden cardiac death medicine.anatomical_structure Desmosome biology.protein Cancer research Medicine business Intermediate filament |
| Zdroj: | Biomedical Research and Therapy. 4:128 |
| ISSN: | 2198-4093 |
| Popis: | Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary disorder of the cardiac muscle characterised by ventricular arrhythmias, cardiac failure and sudden cardiac death. Desmosomes - the intercellular junctions of both epithelial and cardiovascular tissues that connect intermediate filaments of adjacent cells, generating a large and mechanically resilient network - are disordered in ARVC. Here, we exploit new insights into desmoplakin (DP), a critical component of desmosome structures. Indeed, both patient skin and keratinocytes expressing DP mutant construct showed large intercellular aggregates and a decrease in the amount of junctional proteins at areas of cell-cell contact. Moreover, experiments with DP knockout mice indicated that mislocalization of another junctional protein, connexin 43 was ameliorated by b-blocker (beta-blocker), or b-adrenergic receptor blocker - known to interfere with the binding to the receptor of epinephrine and other stress hormones to weaken the effects of stress hormones. Thus, these novel findings fortify the genetic and cellular mechanisms behind the marked heterogeneity of the disease and provide new therapeutic interventions that target intercellular junctions. |
| Databáze: | OpenAIRE |
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