| Long term metabolic arrest and recovery of HEK293 spheroids involves NF-kappaB signaling and sustained JNK activation. | |
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MedLine Citation:
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PMID: 16155929 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Understanding how cells withstand a depletion of intracellular water is relevant to the study of longevity, aging, and quiescence because one consequence of air-drying is metabolic arrest. After removal of medium, HEK293 spheroids with intracellular water content of approximately 65% survived partial vacuum, with antistatic control, for weeks in the dark at 25 degrees C. In contrast, only a limited exposure of monolayers to air was lethal; the mitochondrion being a target of this stress. The pathways activated during the long-term arrest and recovery of spheroids depended on both NF-kappaB signaling and sustained JNK activation. A cyclical cascade, presumably originating from an intercellular stress signal, led to endogenous cytokine production (TNF-alpha, IL-1b, and IL-8) and propagation of the cellular stress signal through the co-activation of NF-kappaB and JNK. Increased levels of downstream pathway signaling members, specifically Gadd45beta, c-jun, and ATF3 were observed, as was activation of c-jun (phosphorylation). Activation of these pathways permit cells to survive long-term storage and recovery because chemical inhibition of both NF-kappaB nuclear translocation and JNK phosphorylation led to cell death. The capacity of an immortalized cell to enter, and then exit, a state of long-term quiescence, without genetic or chemical intervention, has implications for the study of cell transformation. In addition, the ability to monitor the relevant signaling pathways at endogenous levels, from effector to transcriptional regulator, emphasizes the utility of multicellular aggregate models in delineating stress response pathways. |
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Authors:
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Graham D Jack; E Andrew Mead; James F Garst; M Carla Cabrera; Andrea M DeSantis; Stephen M Slaughter; Jody Jervis; Andrew I Brooks; Malcolm Potts; Richard F Helm |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Journal of cellular physiology Volume: 206 ISSN: 0021-9541 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2006 Feb |
Date Detail:
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Created Date: 2005-12-05 Completed Date: 2006-03-10 Revised Date: 2009-11-19 |
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: 526-36 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2005 Wiley-Liss, Inc. |
Affiliation:
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Department of Biochemistry, Virginia Tech Center for Genomics, Virginia Tech, Blacksburg, Virginia, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line Desiccation Down-Regulation Humans MAP Kinase Kinase 4 / metabolism*, physiology Microscopy, Confocal NF-kappa B / metabolism* Polysaccharides / pharmacology* Signal Transduction Spheroids, Cellular / cytology, drug effects, physiology* Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/NF-kappa B; 0/Polysaccharides; EC 2.7.12.2/MAP Kinase Kinase 4 |
| Comments/Corrections | |
Erratum In:
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J Cell Physiol. 2006 Dec;209(3):1055 Note: Mead, E Andrew [removed] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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