期刊
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
卷 76, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2019.108286
关键词
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资金
- United States Department of Agriculture National Institute of Food and Agriculture [2016-67017-24423]
- National Institutes of Health/National Institute of Environmental Health Sciences of United States [R00 ES024806]
- National Science Foundation/National Institute of General Medical Sciences of United States [DMS-1761320]
- Studienstiftung des Deutschen Volkes
Peroxidation of polyunsaturated fatty acids leads to the formation of a large array of lipid-derived electrophiles (LDEs), many of which are important signaling molecules involved in the pathogenesis of human diseases. Previous research has shown that one of such LDEs, trans, trans-2,4-decadienal (tt-DDE), increases inflammation, however, the underlying mechanisms are not well understood. Here we used click chemistry-based proteomics to identify the cellular targets which are required for the pro-inflammatory effects of tt-DDE. We found that treatment with tt-DDE increased cytokine production, JNK phosphorylation, and activation of NF-kappa B signaling in macrophage cells, and increased severity of dextran sulfate sodium (DSS)-induced colonic inflammation in mice, demonstrating its pro-inflammatory effects in vitro and in vivo. Using click chemistry-based proteomics, we found that tt-DDE directly interacts with Hsp90 and 14-3-3 zeta, which are two important proteins involved in inflammation and tumorigenesis. Furthermore, siRNA knockdown of Hsp90 or 14-3-3 zeta abolished the proinflammatory effects of tt-DDE in macrophage cells. Together, our results support that tt-DDE increases inflammatory responses via Hsp90- and 14-3-3 zeta-dependent mechanisms. (C) 2020 Elsevier Inc. All rights reserved.
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