Identification of Protein Targets of 12/15-Lipoxygenase-Derived Lipid Electrophiles in Mouse Peritoneal Macrophages Using Omega-Alkynyl Fatty Acid

The 12/15-lipoxygenase (12/15-LOX) enzyme introduces peroxyl groups, in a position-specific manner, into polyunsaturated fatty acids to form various kinds of bioactive lipid metabolites, including lipid-derived electrophiles (LDE). The resident peritoneal macrophage is the site of highest 12/15-LOX expression in the mouse. However, the role of the enzyme in the regulation of resident macrophages is not fully understood. Here, we describe a chemoproteomic method to identify the targets of enzymatically generated LDE. By treating mouse peritoneal macrophages with omega-alkynyl arachidonic acid (aAA), we identified a series of proteins adducted by LDE generated through a 12/15-LOX catalyzed reaction. Pathway analysis revealed a dramatic enrichment of proteins involved in energy metabolism and found that glycolytic flux and mitochondrial respiration were significantly affected by the expression of 12/15-LOX. Our findings thus highlight the utility of chemoproteomics using aAA for identifying intracellular targets of enzymatically generated LDE

Synthesis and Biological Evaluation of Derivatives of 2-{2-Fluoro-4-[(2-oxocyclopentyl)methyl]phenyl}propanoic Acid: Nonsteroidal Anti-Inflammatory Drugs with Low Gastric Ulcerogenic Activity

We previously reported that 2-fluoroloxoprofen has lower gastric ulcerogenic activity than loxoprofen, a nonsteroidal anti-inflammatory drug (NSAID) without selectivity for COX-2. We synthesized derivatives of 2-fluoroloxoprofen and studied their properties. Compared to 2-fluoroloxoprofen, one derivative, <b>11a</b>, exhibited higher anti-inflammatory activity and an equivalent ulcerogenic effect. These results suggest that <b>11a</b> could be therapeutically beneficial for use as an NSAID

Factors associated with premature termination of CART sessions (univariate analysis).

<p>Factors associated with premature termination of CART sessions (univariate analysis).</p

Amount of reinfused protein and change in urine volume.

<p>There was a significant positive correlation between the amount of reinfused protein and change in the urine volume.</p

Factors influencing the recovery rate of total protein by multivariate analyses.

<p>Factors influencing the recovery rate of total protein by multivariate analyses.</p

Relationship between the filtration-concentration speed and the increase in body temperature.

<p>The increase in body temperature tended to be high when the filtration-concentration speed was high only among the patients with cirrhotic ascites and without concomitant use of steroids/NSAIDs (A). However, no relationship between them was found in malignant ascites regardless of concomitant use of steroids/NSAIDs (B). Circle: with concomitant steroids/NSAIDs. Open triangles: without concomitant steroids/NSAIDs. NSAIDs: non-steroidal anti-inflammatory drugs.</p

Factors associated with fever by multivariate analysis.

<p>Factors associated with fever by multivariate analysis.</p

Changes of clinical indices between pre- and post-CART.

<p>Changes of clinical indices between pre- and post-CART.</p

Filtration-concentration conditions.

<p>Filtration-concentration conditions.</p

Changes in blood test results between pre-and post-CART.

<p>Changes in blood test results between pre-and post-CART.</p