8,9-Epoxyeicosatrienoic acid protects the glomerular filtration barrier. Prostaglandins Other Lipid Mediat 2009 Jun;89(1-2):43-51
Date
05/30/2009Pubmed ID
19480064Pubmed Central ID
PMC2835413DOI
10.1016/j.prostaglandins.2009.04.004Scopus ID
2-s2.0-65649089846 (requires institutional sign-in at Scopus site) 41 CitationsAbstract
Glomerular dysfunction and proteinuria characterize focal segmental glomerulosclerosis (FSGS) associated with chronic kidney disease. FSGS is resistant to treatment and a circulating permeability factor (FSPF) frequently causes post-renal transplantation recurrence. In order to explore the role of 5,6-, 8,9-, 11,12- and 14,15-epoxyeicosatrienoic acids (EETs), we determined their effect on FSPF-induced increase in glomerular albumin permeability (P alb) using an in vitro assay. Exogenous 8,9-EET (1-1000 nM) dose-dependently prevented the FSPF-induced increase in P alb. The other three EET regioisomers, 8,9-EET metabolite, 8,9-dihydroxyeicosatrienoic acid and unrelated 11,14-eicosadienoic acid (100 nM each) were not effective suggesting specificity of the observed glomerular protection by 8,9-EET. Synthetic analogs of 8,9-EET containing one double bond antagonized the effect of 8,9-EET on the FSPF-induced increase in P alb. Analogs containing two double bonds did not antagonize the effect of 8,9-EET and significantly blocked the FSPF-induced increase in P alb. These novel findings suggest a unique protective role for 8,9-EET in the glomerulus. Stable analogs of 8,9-EET may be valuable in developing effective management/treatment of glomerular dysfunction.
Author List
Sharma M, McCarthy ET, Reddy DS, Patel PK, Savin VJ, Medhora M, Falck JRAuthor
Meetha Medhora Professor in the Radiation Oncology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
8,11,14-Eicosatrienoic AcidAnimals
Cattle
Dose-Response Relationship, Drug
Drug Discovery
Glomerulosclerosis, Focal Segmental
Humans
In Vitro Techniques
Kidney Glomerulus
Male
Permeability
Rats
Rats, Sprague-Dawley
Serum Albumin
Stereoisomerism
Structure-Activity Relationship
Vasodilator Agents
