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Mast Cell Chymase Induces Cardiomyocyte Anoikis by a Mechanism Involving Laminin Degradation and Disruption of Focal Adhesion
Author(s) -
Zheng Junying,
Powell Pamela C.,
Pat Betty,
Dell’Italia Louis A.,
Killingsworth Cheryl R.,
Dell’Italia Louis J.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1179.2
Subject(s) - chymase , anoikis , laminin , extracellular matrix , chemistry , fibronectin , microbiology and biotechnology , focal adhesion , mast cell , apoptosis , proteases , cell , programmed cell death , immunology , biology , biochemistry , enzyme
Loss of cardiomyocytes plays a causal role in the development of heart failure. Adhesion to glycoproteins of the extracellular matrix (ECM) is necessary for survival of the cardiomyocytes in the heart. Proteases are able to degrade glycoproteins and induce anoikis of adherent cells. Mast cells contain various proteases such as chymase. In mitral regurgitation (MR) dogs, there is an increase of mast cell infiltration and degranulation. In addition, chymase activity is elevated in early MR and remains elevated throughout the course of MR. In this experiment, dog myocytes were treated with various doses of chymase (0.1, 1.0, and 10 <μ>g/ml), each at a time course of 1, 4, 12, and 24 hours. After treatment, cells showed decreased attachment to laminin with a progressive increase in chymase concentration of 0.1 to 10 <μ>g/ml. At 24 hours, 70% of cells were detached after treatment with 10 <μ>g/ml of chymase, while > 90% of untreated cardiomyocytes remained. Detection of cleaved caspase‐3 indicated that detached cells were undergoing apoptosis. Focal adhesion kinase, one of the key mediators of integrin–ECM interactions was rapidly degraded in the presence of chymase. Separate experiments demonstrated that chymase concentration dependently degraded laminin. These results suggest that chymase can mediate anoikis of dog cardiomyocytes through a mechanism involving degradation of laminin and cell/matrix interactions.