title: Human aquaporin adipose (AQPap) gene. Genomic structure, promoter analysis and functional mutation.
abstract: Aquaporin adipose (AQPap), which we identified from human adipose tissue, is a glycerol channel in adipocyte [Kishida et al. (2000) J. Biol. Chem. 275, 20896-20902]. In the current study, we determined the genomic structure of the human AQPap gene, and identified three AQPap-like genes that resembled (approximately 95%) AQPap, with little expression in human tissues. The AQPap promoter contained a putative peroxisome proliferator response element (PPRE) at -46 to -62, and a putative insulin response element (IRE) at -542/-536. Deletion of the PPRE abolished the pioglitazone-mediated induction of AQPap promoter activity in 3T3-L1 adipocytes. Deletion and single base pair substitution analysis of the IRE abolished the insulin-mediated suppression of the human AQPap gene. Analysis of AQPap sequence in human subjects revealed three missense mutations (R12C, V59L and G264V), and two silent mutations (A103A and G250G). The cRNA injection of the missense mutants into Xenopus oocytes revealed the absence of the activity to transport glycerol and water in the AQPap-G264V protein. In the subject homozygous for AQPap-G264V, exercise-induced increase in plasma glycerol was not observed in spite of the increased plasma noradrenaline. We suggest that AQPap is responsible for the increase of plasma glycerol during exercise in humans.
authors.affiliation: Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Yamadaoka, Suita, Japan.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Kondo
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.forename: Ken
authors.initials: K
authors.lastname: Kishida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kuriyama
authors.forename: Yasunaka
authors.initials: Y
authors.lastname: Makino
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nishizawa
authors.forename: Morihiro
authors.initials: M
authors.lastname: Matsuda
authors.forename: Norikazu
authors.initials: N
authors.lastname: Maeda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nagaretani
authors.forename: Shinji
authors.initials: S
authors.lastname: Kihara
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kurachi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D020346:Aquaporins / Q000235:genetics*; D001483:Base Sequence; D015139:Blotting, Southern; D015153:Blotting, Western; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D017931:DNA Primers; D005091:Exons; D006801:Humans; D006822:Hybrid Cells / Q000528:radiation effects; D007438:Introns; D009154:Mutation; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C114141:AQP7 protein, human; D020346:Aquaporins; D017931:DNA Primers