title: Disorder of fatty acid metabolism in the kidney of PAN-induced nephrotic rats.
abstract: Proteinuria is considered to play an essential role in the progression of tubulointerstitial damage, which causes end-stage renal disease. Fatty acid-binding albumins are filtered through glomeruli and reabsorbed into proximal tubular epithelial cells (PTECs). However, the role of fatty acid metabolism associated with albuminuria in the development of tubulointerstitial damage remains unclear. Thus, the present study was designed to determine the changes of fatty acid metabolism in the nephrotic kidney. To induce nephrotic syndrome, Sprague-Dawley rats (SDRs) and Nagase analbuminemic rats (NARs) with inherited hypoalbuminemia were treated with a single injection of puromycin aminonucleoside (PAN). In SDRs, PAN treatment induced massive proteinuria and albuminuria and caused tubular damage, apoptosis, and lipid accumulation in PTECs. Among the enzymes of fatty acid metabolism, expressions of medium-chain acyl-CoA dehydrogenase (MCAD) and cytochrome P-450 (CYP)4A significantly decreased in PTECs of PAN-treated SDRs. Expressions of peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)-1α and estrogen-related receptor (ERR)α also significantly decreased, without changes in the expression of PPAR-α. In NARs, PAN treatment induced proteinuria but not albuminuria and did not cause tubular damage, apoptosis, or lipid accumulation. Expressions of MCAD, PGC-1α, or ERRα did not change in the kidney cortex of PAN-treated NARs, but the expression of CYP4A significantly decreased. These results indicate that massive albuminuria causes tubular damage and lipid accumulation with the reduction of MCAD, CYP4A, PGC-1α, and ERRα in PTECs.
authors.affiliation: Dept. of Internal Medicine and Rehabilitation Science, Tohoku Univ. Graduate School of Medicine, 1-1 Seiryo-chyo, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Muroya
authors.forename: Osamu
authors.initials: O
authors.lastname: Ito
authors.forename: Rong
authors.initials: R
authors.lastname: Rong
authors.forename: Kenta
authors.initials: K
authors.lastname: Takashima
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ito
authors.forename: Pengyu
authors.initials: P
authors.lastname: Cao
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Kensuke
authors.initials: K
authors.lastname: Joh
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kohzuki
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000378:metabolism; D000818:Animals; D042926:Cytochrome P-450 CYP4A / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism*; D011692:Puromycin Aminonucleoside; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D042964:Acyl-CoA Dehydrogenase; D042926:Cytochrome P-450 CYP4A; D005227:Fatty Acids; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011692:Puromycin Aminonucleoside; D016601:RNA-Binding Proteins; D011960:Receptors, Estrogen; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; C501429:Ppargc1a protein, rat