Document Detail


The nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide affects stress response and fate of lipopolysaccharide-primed RAW 264.7 macrophage cells.
MedLine Citation:
PMID:  23053730     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) is commonly used to study free radicals. Due to its free radical trapping properties, DMPO is thought to reduce free radial-mediated oxidative damage and other related cellular responses. The purpose of this study was to assess the effect of DMPO on lipopolysaccharide (LPS)-induced inflammation, endoplasmic reticulum (ER) stress, and apoptosis in RAW 264.7 cells. The results showed that DMPO at 50 mM inhibited inducible nitric oxide synthase expression when added shortly after LPS treatment (≤3 h). Interestingly, DMPO increased anti-inflammatory heme oxygenase-1 (HO-1) expression and reversed LPS-induced decrease in HO-1 expression. LPS could increase cellular ER stress as indicated by C/EBP homologous protein (CHOP) induction; DMPO reduced LPS effect on CHOP expression. Unexpectedly, DMPO had a synergistic effect with LPS on increased caspase-3 activity. Overall, DMPO harbors multiple modulating effects but may induce apoptosis in LPS-stressed cells when given at 50 mM, an effective dose for its anti-inflammatory activity in vitro. Our data provide clues for further understanding of the nitrone spin trap with therapeutic potential.
Authors:
Zili Zhai; Sandra E Gomez-Mejiba; Dario C Ramirez
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Inflammation     Volume:  36     ISSN:  1573-2576     ISO Abbreviation:  Inflammation     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-08     Completed Date:  2013-08-23     Revised Date:  2014-07-03    
Medline Journal Info:
Nlm Unique ID:  7600105     Medline TA:  Inflammation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  346-54     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
14-3-3 Proteins / metabolism
Animals
Apoptosis / drug effects*
Caspase 3 / metabolism
Cell Line
Cyclic N-Oxides / pharmacology*
Endoplasmic Reticulum / drug effects,  metabolism*
Free Radicals / metabolism
Heme Oxygenase-1 / biosynthesis,  drug effects
Inflammation / chemically induced
Lipopolysaccharides
Macrophages / immunology,  metabolism*
Membrane Proteins / biosynthesis,  drug effects
Mice
Nitric Oxide Synthase Type II / biosynthesis,  drug effects
Nitrogen Oxides / chemistry
Proto-Oncogene Proteins c-bcl-2 / metabolism
Spin Labels
Spin Trapping
Stress, Physiological
Transcription Factor CHOP / biosynthesis,  drug effects
Grant Support
ID/Acronym/Agency:
5R00ES015415-04/ES/NIEHS NIH HHS; R00 ES015415/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/14-3-3 Proteins; 0/Cyclic N-Oxides; 0/Ddit3 protein, mouse; 0/Free Radicals; 0/Lipopolysaccharides; 0/Membrane Proteins; 0/Nitrogen Oxides; 0/Proto-Oncogene Proteins c-bcl-2; 0/Spin Labels; 0/nitrones; 147336-12-7/Transcription Factor CHOP; 7170JZ1QF3/5,5-dimethyl-1-pyrroline-1-oxide; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.99.3/Heme Oxygenase-1; EC 1.14.99.3/Hmox1 protein, mouse; EC 3.4.22.-/Caspase 3
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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