title: Identification of functions of peroxisome proliferator-activated receptor alpha in proximal tubules.
abstract: Peroxisome proliferator-activated receptor alpha(PPARalpha) is a member of the steroid/nuclear receptor superfamily that is intensively expressed in the kidney, but its physiologic function is unknown. In this study, PPARalpha-null mice were used to help clarify the function. Starved PPARalpha-null mice were found to secrete significantly more quantities of urine albumin than starved wild-type mice. Furthermore, the appearance of giant lysosomes, marked accumulation of albumin, and an impaired ability concerning albumin digestion were found only in proximal tubules of the starved PPARalpha-null mice. These abnormalities were probably derived from ATP insufficiency as a result of the starvation-induced decline of carbohydrate metabolism and a lack of PPARalpha-dependent fatty acid metabolism. It is interesting that these abnormalities disappeared when glucose was administered. Taken together, these findings demonstrate important functions of PPARalpha in the proximal tubules, the dynamic regulation of the protein-degradation system through maintenance of ATP homeostasis, and emphasize the importance of the fatty acid metabolism in renal physiology.
authors.affiliation: Department of Aging Biochemistry, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Nagano, Japan. yujibeat@hsp.md
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kamijo
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hora
authors.forename: Naoki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Nobuteru
authors.initials: N
authors.lastname: Usuda
authors.forename: Kendo
authors.initials: K
authors.lastname: Kiyosawa
authors.forename: Tamie
authors.initials: T
authors.lastname: Nakajima
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Aoyama
mesh_terms: D000255:Adenosine Triphosphate / Q000172:deficiency; D000419:Albuminuria / Q000209:etiology; D000818:Animals; D007687:Kidney Tubules, Proximal / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D013217:Starvation / Q000473:pathology / Q000503:physiopathology* / Q000652:urine; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000255:Adenosine Triphosphate