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The Role of TLRs in Cardiac Myocyte Apoptosis
Author(s) -
Heiserman James P.,
Chen Le,
Kim BumSoo,
Kim SeChan,
Tran Alice,
Siebenborn Nina,
Knowlton Anne A.
Publication year - 2013
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.27.1_supplement.652.11
Subject(s) - myocyte , apoptosis , tlr2 , chemistry , receptor , nadph oxidase , medicine , tlr4 , endocrinology , antibody , hypoxia (environmental) , cardiac myocyte , microbiology and biotechnology , biology , reactive oxygen species , immunology , oxygen , biochemistry , organic chemistry
Recently, Toll‐like receptors(TLRs) have been investigated for their role in apoptosis. Previously we have shown that low endotoxin extracellular(ex) HSP60 causes cardiac myocyte apoptosis, and we hypothesized that this would be blocked in cardiomyocytes that have nonfunctioning TLR4. Methods We studied adult cardiac myocytes from C3H/HeJ mice, which have a mutant, nonfunctional TLR4, and compared the results with parallel studies in adult cardiac myocytes from wild type (WT) mice. We also looked at the response of WT mouse cardiomyocytes to hypoxia/reoxygenation(H/R) in the presence of TLR2 and TLR4 blocking antibodies. LDH release and NADPH Oxidase 2 (NOX2) activity were endpoints. Results We found exHSP60 caused apoptosis in WT, but not TLR4 mutant cardiomyocytes, based on increased DNA fragmentation and caspase3 activation. In experiments with WT myocytes treated with TLR2 and 4 blocking antibodies with H/R, LDH release was decreased by either blocking antibody. NOX2 activity increased in control cells with H/R and was decrease in WT cardiomyocytes treated with TLR2 and 4 blocking antibodies, suggesting TLR2/4 mediate increased NOX2 activity in H/R injury.