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Increase toll‐like receptor 4 expression after ischemia/reperfusion contributes to myocardial apoptosis: role of PI3Kγ/NFκB pathway
Author(s) -
Xu Hu,
Xu Xuemei,
Zhang Jingchao,
Su Zhaoliang,
Martin Claudio M.,
Rui Tao
Publication year - 2010
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.24.1_supplement.110.5
Subject(s) - tlr4 , apoptosis , pi3k/akt/mtor pathway , myocyte , phosphorylation , cardiac myocyte , signal transduction , receptor , microbiology and biotechnology , chemistry , medicine , endocrinology , biology , biochemistry
This study is to explore increase toll‐like receptor 4 (TLR4) expression and its regulation pathway in the ischemia/reperfusion (I/R) ‐induced myocardial apoptosis. Methods TLR4 expression, PI3Kγ, NFκB and apoptosis were assessed in cardiac myocytes challenged with an anoxia/reoxygenation (A/R). In vivo, mice were subjected to coronary artery occlusion followed by releasing for myocardial I/R. Myocardial TLR4 expression, apoptosis were evaluated. Results A/R challenge resulted in increased TLR4 expression and myocyte apoptosis. Myocytes deficient in TLR4 did not show increase in myocyte apoptosis after A/R. PI3Kγ and p65 (a subunit of NFκB were phosphorylated in cardiomyocytes with A/R. The phosphorylation of p65 occurred after PI3Kγ. A/R‐induced p65 phosphorylation did not occur in myocytes deficient in PI3Kγ. Pretreatment of myocytes with MG132, an inhibitor of NFκB, prevented the A/R‐induced increase in TLR4 expression. I/R resulted in increase myocardial TLR4 expression and apoptosis. I/R‐induced myocardial apoptosis was attenuated in mice deficient in TLR4 and PI3Kγ. Conclusion Our results indicate increase in TLR4 expression contributes to I/R‐induced myocardial apoptosis. PI3Kγ/NFκB signaling pathway is pivotal in regulating TLR4 expression. (HSFO NA 6316)