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Modified LDL activates JNK‐2 phosphorylation and colocalization with mitochondria
Author(s) -
Hamilton Ryan T,
Asatryan Liana,
Zhou Qiongqiong,
Cadenas Enrique,
Hsiai Tzung
Publication year - 2007
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.21.6.a853-c
Subject(s) - colocalization , phosphorylation , mitochondrion , peroxynitrite , kinase , chemistry , western blot , microbiology and biotechnology , oxidative phosphorylation , biochemistry , biology , superoxide , enzyme , gene
Modified LDL initiates the pathogenesis of atherosclerosis. JNK‐2 protein kinase knockout mice harbor a decrease in macrophage foam cell formation, and our laboratory has shown that p‐JNK‐1 regulates pyruvate dehydrogenase activity in neuron mitochondria. We assessed whether modified LDL activates JNK‐2 phosphorylation and mitochondrial colocalization. Methods and Results: Modified LDL particles (10μg/ml), including peroxynitrite‐, copper‐ and PLA2‐treated LDL, were incubated with bovine aortic endothelial cells in the presence or absence of JNK inhibitor. Western blot analyses showed a 1.50±0.24‐fold increase in p‐JNK‐2 in response to copper‐treated LDL (n=3, P <0.05), 1.39±0.18‐fold increase in response to peroxynitrite‐treated LDL (n=3, P <0.05), and a 1.32±0.11‐fold increase in response to PLA2‐treated LDL (n=3, P < 0.05). Modified LDL induced p‐JNK‐2 localization to the mitochondria and treatment with JNK inhibitor blocked p‐JNK‐2 localization to the mitochondria. Conclusion: Our findings demonstrate that modified LDL particles induce JNK‐2 phosphorylation and p‐JNK‐2 localization to the mitochondria, suggesting that p‐JNK‐2 may be involved in mitochondrial activities.