Publication Date:
2013-10-30
Description:
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- κ B, 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- κ B. Anti-KChIP2 (C-12)-treatment for two hours significantly reduced KChIP2 mRNA and protein expression. Anti-KChIP2 (C-12) induced nuclear translocation of NF- κ B after one hour. After six hours, Δψm and caspase-3 and -9 activities were not significantly changed. After 24 hours, 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 five minutes. 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. © 2013 Wiley Periodicals, Inc.
Electronic ISSN:
0091-7419
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
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