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Human aquaporin adipose (AQPap) gene. Genomic structure, promoter analysis and functional mutation

Human aquaporin adipose (AQPap) gene. Genomic structure, promoter analysis and functional mutation

Authors :
Shinji Kihara
Tadashi Nakamura
Hiroyuki Nagaretani
Hitoshi Nishizawa
Norikazu Maeda
Iichiro Shimomura
Yasunaka Makino
Hidehiko Kondo
Ken Kishida
Yuji Matsuzawa
Hiroshi Kuriyama
Tohru Funahashi
Yoshihisa Kurachi
Morihiro Matsuda
Source :
European journal of biochemistry. 269(7)
Publication Year :
2002

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.

Details

ISSN :
00142956
Volume :
269
Issue :
7
Database :
OpenAIRE
Journal :
European journal of biochemistry
Accession number :
edsair.doi.dedup.....59c339ac257aa4569c4f688f79396a5d