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Antibodies Against Potassium Channel Interacting Protein 2 Induce Necrosis in Isolated Rat Cardiomyocytes
Author(s) -
Choudhury Sangita,
Schnell Michael,
Bühler Thomas,
Reinke Yvonne,
Lüdemann Jan,
Nießner Felix,
Brinkmeier Heinrich,
Herda Lars R.,
Staudt Alexander,
Kroemer Heyo K.,
Völker Uwe,
Felix Stephan B.,
Landsberger Martin
Publication year - 2014
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24707
Subject(s) - apoptosis , programmed cell death , necrosis , antibody , chromosomal translocation , chemistry , caspase , microbiology and biotechnology , cell , caspase 3 , myocyte , medicine , endocrinology , biology , biochemistry , immunology , gene
Auto‐antibodies against cardiac proteins have been described in patients with dilated cardiomyopathy. Antibodies against the C‐terminal part of KChIP2 (anti‐KChIP2 [C‐12]) enhance cell death of rat cardiomyocytes. The underlying mechanisms are not fully understood. Therefore, we wanted to explore the mechanisms responsible for anti‐KChIP2‐mediated cell death. Rat cardiomyocytes were treated with anti‐KChIP2 (C‐12). KChIP2 RNA and protein expressions, nuclear NF‐κB, mitochondrial membrane potential Δψm, caspase‐3 and ‐9 activities, necrotic and apoptotic cells, total Ca 2+ and K + concentrations, and the effects on L‐type Ca 2+ channels were quantified. Anti‐KChIP2 (C‐12) induced nuclear translocation of NF‐κB. Anti‐KChIP2 (C‐12)‐treatment for 2 h significantly reduced KChIP2 mRNA and protein expression. Anti‐KChIP2 (C‐12) induced nuclear translocation of NF‐κB after 1 h. After 6 h, Δψm and caspase‐3 and ‐9 activities were not significantly changed. After 24 h, anti‐KChIP2 (C‐12)‐treated cells were 75 ± 3% necrotic, 2 ± 1% apoptotic, and 13 ± 2% viable. Eighty‐six ± 1% of experimental buffer‐treated cells were viable. Anti‐KChIP2 (C‐12) induced significant increases in total Ca 2+ (plus 11 ± 2%) and K + (plus 18 ± 2%) concentrations after 5 min. Anti‐KChIP2 (C‐12) resulted in an increased Ca 2+ influx through L‐type Ca 2+ channels. In conclusion, our results suggest that anti‐KChIP2 (C‐12) enhances cell death of rat cardiomyocytes probably due to necrosis. J. Cell. Biochem. 115: 678–689, 2014. © 2013 Wiley Periodicals, Inc.