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In cardiomyocytes LPS‐induced activation of IκBα and COX‐2 expression are mediated in part by the hexosamine biosynthesis pathway
Author(s) -
Lu Xiaoyin Tina,
Zou Luyun,
Chatham John C
Publication year - 2012
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.26.1_supplement.1136.7
Subject(s) - biosynthesis , chemistry , inflammation , endocrinology , medicine , lipopolysaccharide , signal transduction , microbiology and biotechnology , biochemistry , enzyme , biology
We have previously reported that hyperglycemia (HG) augmented the induction iNOS by LPS and this was due at least in part by increased flux through the hexosamine biosynthesis pathway (HBP). COX2 is induced by a number of stresses such as ischemia, pro‐inflammation cytokines, and mitogenic responses and this is regulated in part by NF‐κB signaling. Therefore, the goal of this study was to determine if in neonatal rat ventricular cardiomyocytes (NRVM) COX2 expression was also regulated by the HBP. LPS treatment for 6hrs (2μg/ml) significantly increased both P‐IκBα and COX2 expression in NRVM and whereas HG augmented the LPS‐induced increase in P‐IκBα its effect on COX2 was less pronounced. Interestingly however, inhibition of GFAT with either DON (20 μM) or Azserine (40 μM) substantially decreased the LPS‐induced increased COX‐2 and P‐IκBα both under normal and HG conditions. These results suggest that activation of the HBP contributes to the pro‐inflammatory effects of LPS and that this is augmented at least in part under HG conditions.