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8,9‐Dihydroxyeicosatrienoic acid does not protect the glomerular filtration barrier
Author(s) -
Sharma Mukut,
McCarthy Ellen T,
Savin Virginia J,
Patel Paresh,
Shaw Sean,
Falck John R,
Imig John D
Publication year - 2009
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.23.1_supplement.lb370
Subject(s) - epoxide hydrolase 2 , chemistry , focal segmental glomerulosclerosis , endocrinology , metabolite , medicine , renal function , proteinuria , kidney , biochemistry , enzyme
Focal segmental glomerulosclerosis (FSGS) leads to end‐stage renal disease. A circulating factor is believed to cause the primary glomerular lesion in FSGS. We have shown that 8,9‐epoxyeicosatrienoic acid (8,9‐EET) protects the glomerular filtration barrier function against the FSGS factor. Presently, we hypothesized that 8,9‐dihydroxyeicosatrienoic acids (8,9‐DiHETrE), vic‐diol of 8,9‐EET produced by soluble (sEH) epoxide hydrolase, is responsible for the observed protective effect of 8,9‐EET. Methods We determined the change in glomerular albumin permeability (P alb ) in vitro following incubation of rat glomeruli with FSGS‐plasma, FSGS + 8,9‐EET, FSGS + 8,9‐DiHETrE, FSGS + sEH inhibitor AUDA (1‐10 microM) for 15 minutes at 37°C (n=15 in each group). Glomerular sEH protein expression was determined by immunoblotting. Results FSGS plasma‐induced increase in P alb (P<0.001 vs. vehicle control) was completely blocked by exogenous 100 nM 8,9‐EET (P<0.001 vs. FSGS) while its metabolite 8,9‐DiHETrE (200 nM) did not cause a significant decrease in P alb (P<0.1 vs. FSGS). AUDA at 1 microM showed a protective effect on Palb against FSGS plasma (P<0.001 vs. FSGS) but 10 microM AUDA did not. Immunoblot analysis showed a relatively weak protein expression of sEH in glomeruli. Summary and Conclusions 8,9‐EET and AUDA, but not 8,9‐DiHETrE, attenuated the FSGS‐induced increase in P alb . Results suggest that EET metabolism in the glomerulus may be cell‐type specific. We conclude that 8,9‐EET protects against FSGS‐induced glomerular injury and that its vicinal diol 8,9‐DiHETErE does not contribute to the protective effect.