TY - JOUR
T1 - 8,9-Epoxyeicosatrienoic acid protects the glomerular filtration barrier
AU - Sharma, Mukut
AU - McCarthy, Ellen T.
AU - Reddy, D. Sudarshan
AU - Patel, Paresh K.
AU - Savin, Virginia J.
AU - Medhora, Meetha
AU - Falck, John R.
N1 - Funding Information:
Financial support for these studies was provided in part by NIH/NIDDK 061588 (ETM), NIH/NIDDK 064969 (ETM), NIH HL 69996 (MM), GM31278 (JRF), the Robert A. Welch Foundation (JRF) and the Department of Medicine, Medical College of Wisconsin, Milwaukee (MS).
PY - 2009/6
Y1 - 2009/6
N2 - 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.
AB - 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.
KW - 8,9-EET
KW - Albumin permeability
KW - Chronic kidney disease
KW - Epoxyeicosatrienoic acids
KW - FSGS
KW - Glomerular filtration barrier
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U2 - 10.1016/j.prostaglandins.2009.04.004
DO - 10.1016/j.prostaglandins.2009.04.004
M3 - Article
C2 - 19480064
AN - SCOPUS:65649089846
SN - 1098-8823
VL - 89
SP - 43
EP - 51
JO - Prostaglandins and Other Lipid Mediators
JF - Prostaglandins and Other Lipid Mediators
IS - 1-2
ER -