| Lipopolysaccharide induces autophagy through BIRC2 in human umbilical vein endothelial cells. | |
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MedLine Citation:
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PMID: 20458734 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Lipopolysaccharide (LPS), as an important proinflammatory agent, targets the endothelium. However, almost all in vitro experiments of the effect of LPS on vascular endothelial cells (VECs) were performed under an artificially decreased concentration of serum that was not enough to maintain the cell growth for a long time. The mechanism underlying LPS action on VECs cultured in a nutrient-rich condition is not clear. To address this question and mimic the in vivo condition, we investigated the effect of LPS on VEC autophagy, which is involved in numerous physiological processes. The effect of LPS on microtubule-associated protein 1 light chain 3 (LC3) distribution, LC3-II accumulation and p62 degradation showed that LPS effectively induced autophagy in VECs cultured in the presence of 20% serum. To understand the mechanism by which LPS triggers the cell autophagy, we first investigated the effects of LPS on the expression of BIRC2 (cIAP1), a well-known apoptosis inhibitor, and on the kinase activity of mammalian target of rapamycin (mTOR) and nuclear translocation of p53. LPS increased BIRC2 expression in a dose- and time-dependent manner and elevated the intranuclear level of p53 but had no effect on the mTOR pathway when it triggered VEC autophagy. Furthermore, knockdown of BIRC2 by RNA interference inhibited the autophagy and the translocation of p53 to nuclei induced by LPS. These data suggest a novel role for BIRC2 in LPS-induced autophagy in VECs. |
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Authors:
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Ning Meng; LingLing Wu; JiaNgang Gao; Jing Zhao; Le Su; Hua Su; ShangLi Zhang; JunYing Miao |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cellular physiology Volume: 225 ISSN: 1097-4652 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-07-21 Completed Date: 2010-09-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 174-9 Citation Subset: IM |
Copyright Information:
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(c) 2010 Wiley-Liss, Inc. |
Affiliation:
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Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Active Transport, Cell Nucleus
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drug effects Animals Autophagy / drug effects*, physiology Cell Line Cell Survival / drug effects Endothelial Cells / cytology, drug effects*, metabolism Fibroblast Growth Factor 2 / pharmacology Humans Inhibitor of Apoptosis Proteins / genetics, metabolism* Intracellular Signaling Peptides and Proteins / genetics, metabolism Lipopolysaccharides / pharmacology* Protein-Serine-Threonine Kinases / genetics, metabolism RNA Interference Tumor Suppressor Protein p53 / genetics, metabolism Umbilical Veins / cytology* |
| Chemical | |
Reg. No./Substance:
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0/BIRC2 protein, human; 0/Inhibitor of Apoptosis Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/Lipopolysaccharides; 0/Tumor Suppressor Protein p53; 103107-01-3/Fibroblast Growth Factor 2; EC 2.7.1.-/mTOR protein; EC 2.7.11.1/Protein-Serine-Threonine Kinases |
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