8,9-Epoxyeicosatrienoic acid protects the glomerular filtration barrier

Mukut Sharma, Ellen T. McCarthy, D. Sudarshan Reddy, Paresh K. Patel, Virginia J. Savin, Meetha Medhora, John R. Falck

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

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 (Palb) using an in vitro assay. Exogenous 8,9-EET (1-1000 nM) dose-dependently prevented the FSPF-induced increase in Palb. 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 Palb. Analogs containing two double bonds did not antagonize the effect of 8,9-EET and significantly blocked the FSPF-induced increase in Palb. 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.

Original languageEnglish (US)
Pages (from-to)43-51
Number of pages9
JournalProstaglandins and Other Lipid Mediators
Volume89
Issue number1-2
DOIs
StatePublished - Jun 2009

Keywords

  • 8,9-EET
  • Albumin permeability
  • Chronic kidney disease
  • Epoxyeicosatrienoic acids
  • FSGS
  • Glomerular filtration barrier

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

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