RRC ID 44367
Author Shimo T, Adachi Y, Yamanouchi S, Tsuji S, Kimata T, Umezawa K, Okigaki M, Takaya J, Ikehara S, Kaneko K.
Title A novel nuclear factor κB inhibitor, dehydroxymethylepoxyquinomicin, ameliorates puromycin aminonucleoside-induced nephrosis in mice.
Journal Am J Nephrol
Abstract BACKGROUND/AIMS:Minimal-change nephrotic syndrome (MCNS) is a kidney disease defined by selective proteinuria and hypoalbuminemia occurring in the absence of cellular glomerular infiltrates or immunoglobulin deposits. Recent observations suggest that nuclear factor κB (NF-κB) of podocyte is strongly associated with the development of proteinuria in MCNS. Dehydroxymethylepoxyquinomicin (DHMEQ) is a novel NF-κB inhibitor that potently inhibits DNA-binding activity of NF-κB, resulting in several therapeutic effects in various pathological conditions. We conducted this study to ask whether DHMEQ may ameliorate the nephrosis in mice induced by puromycin aminonucleoside (PAN), which is considered to be an animal model for MCNS.
METHODS/RESULTS:Pretreatment with DHMEQ alleviated the proteinuria and reversed the serum abnormalities in mice nephrosis induced by 450 mg/kg of PAN. Increased serum interleukin-6 level in PAN-induced nephrosis was also completely suppressed by DHMEQ. Electron microscopic analyses of glo-meruli indicated that DHMEQ can inhibit the podocyte foot process effacement via blocking the translocation of podocyte NF-κB from cytoplasm to nucleus.
CONCLUSIONS:These results suggest that DHMEQ can be a potential therapeutic agent for MCNS.
Volume 37(4)
Pages 302-9
Published 2013-1-1
DOI 10.1159/000348803
PII 000348803
PMID 23548793
MeSH Adenosine Deaminase / metabolism Albuminuria / urine Animals Benzamides / administration & dosage* Blood Proteins / analysis Cholesterol / blood Cyclohexanones / administration & dosage* Glycerolphosphate Dehydrogenase / metabolism Interleukin-6 / blood Intracellular Signaling Peptides and Proteins / metabolism Kidney / pathology Male Membrane Proteins / metabolism Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Inbred C57BL NF-kappa B / antagonists & inhibitors* NF-kappa B / metabolism Nephrosis / chemically induced Nephrosis / metabolism Nephrosis / pathology Nephrosis / prevention & control* Proteinuria / urine Puromycin Aminonucleoside / toxicity* Rats Serum Albumin / analysis
IF 3.411
Times Cited 13
Human and Animal Cells TKD2(RCB0752)