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Ursolic Acid Protects Monocytes Against Priming and Dysfunction Induced by Metabolic Stress by Preventing Induction of Nox4
Author(s) -
Ullevig Sarah Lynn,
Kim Hong Seok,
Hambright William Sealy,
Tavakoli Sina,
Asmis Reto
Publication year - 2013
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.27.1_supplement.637.17
Subject(s) - nox4 , oxidative stress , chemistry , monocyte , ursolic acid , nadph oxidase , microbiology and biotechnology , biochemistry , pharmacology , biology , immunology , chromatography
We showed that mice fed at high‐fat diet (HFD) supplemented with ursolic acid (UA), an anti‐inflammatory phytochemical, were protected against atherosclerosis and monocyte dysfunction. Here we determine the molecular mechanism by which UA prevents metabolic stress‐induced monocyte priming and dysfunction. UA (0.3. 1, 3, 10 μM) protected THP‐1 monocytes against the sensitizing effect of metabolic stress on MCP‐1‐induced chemotaxis. Metabolically stressed monocytes treated with UA showed a decrease in total protein‐ and actin‐ S ‐glutathionylation, measures of thiol oxidative stress. MAPK phosphatase‐1 protein expression and phosphatase activity, reduced by metabolic stress, were rescued if UA was present during metabolic priming. UA treatment did not change protein and mRNA expression of glutaredoxin‐1, an enzyme that reduces glutathionylated proteins. However, UA blocked metabolic stress induction of Nox4. We therefore propose that UA prevents monocyte priming and dysfunction by suppressing Nox‐4 induction, thereby, preventing Nox4‐dependent dysregulation of redox‐sensitive processes, including actin turnover and MAPK‐signaling. These studies provide a novel mechanism of action for the anti‐inflammatory properties of UA. Funded by NIH RO1 HL070963 & HL115858 (RA). Grant Funding Source : NIH RO1 HL070963 & HL115858