title: A novel nuclear factor κB inhibitor, dehydroxymethylepoxyquinomicin, ameliorates puromycin aminonucleoside-induced nephrosis in mice.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Pediatrics, Kansai Medical University, Osaka, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Shimo
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Adachi
authors.forename: Sohsaku
authors.initials: S
authors.lastname: Yamanouchi
authors.forename: Shoji
authors.initials: S
authors.lastname: Tsuji
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kimata
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Okigaki
authors.forename: Junji
authors.initials: J
authors.lastname: Takaya
authors.forename: Susumu
authors.initials: S
authors.lastname: Ikehara
authors.forename: Kazunari
authors.initials: K
authors.lastname: Kaneko
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism; D000419:Albuminuria / Q000652:urine; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage*; D001798:Blood Proteins / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D003512:Cyclohexanones / Q000008:administration & dosage*; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009401:Nephrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011507:Proteinuria / Q000652:urine; D011692:Puromycin Aminonucleoside / Q000633:toxicity*; D051381:Rats; D012709:Serum Albumin / Q000032:analysis
chemical_list: D001549:Benzamides; D001798:Blood Proteins; D003512:Cyclohexanones; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016328:NF-kappa B; C407223:NPHS2 protein; D012709:Serum Albumin; C464444:dehydroxymethylepoxyquinomicin; C113267:nephrin; D011692:Puromycin Aminonucleoside; D002784:Cholesterol; D005993:Glycerolphosphate Dehydrogenase; D000243:Adenosine Deaminase