Posttranscriptional control of aquaporin-2 abundance by vasopressin in renal collecting duct principal cells

American Journal of Physiology - Renal Physiology - Tập 290 Số 1 - Trang F177-F187 - 2006
Udo Hasler1, Søren Nielsen2, Eric Féraille, Pierre‐Yves Martin
1Service de Néphrologie, Fondation pour Recherches Médicales, 64 Ave. de la Roseraie, CH-1211, Genève 4, Switzerland.
2Aarhus University

Tóm tắt

Prevailing expression levels of aquaporin-2 (AQP2) mRNA play a major role in regulating AQP2 protein abundance. Here, we investigated whether AQP2 protein abundance is regulated at a posttranscriptional level as well. The expression levels of both AQP2 mRNA and protein increase in response to arginine vasopressin (AVP) in a concentration- and time-dependent manner in cultured immortalized mouse collecting duct principal cells (mpkCCDcl4cells). AVP washout from the medium of AVP-pretreated cells revealed that AQP2 mRNA expression progressively decreased over time, whereas AQP2 protein abundance first increased immediately after AVP washout and then gradually decreased over time. Inversely, increasing AVP concentration led to a time-dependent increase of AQP2 mRNA, whereas AQP2 protein abundance first decreased immediately after AVP supplementation and then gradually increased over time. These transient effects arose from altered V2-receptor activity because they could be abolished by SR-121463B, a specific V2-receptor antagonist. Although cycloheximide administration had no effect on transient alterations of AQP2 protein content, these effects were attenuated by administration of chloroquine, a lysosomal inhibitor, or lactacystin, a proteasomal inhibitor. Short-term inhibition of PKA activity significantly increased AQP2 protein abundance and blunted the transient alterations of AQP2 protein content induced by AVP washout and supplementation. In addition, phosphorylated AQP2 abundance increased immediately after AVP supplementation. These results indicate that in response to AVP AQP2 protein abundance in collecting duct principal cells is principally influenced by AQP2 mRNA content but is additionally regulated by PKA-dependent negative feedback acting on AQP2 protein degradation.

Từ khóa


Tài liệu tham khảo

10.1152/ajprenal.2001.280.3.F513

10.1152/ajprenal.2000.279.4.F655

10.1002/hep.1840210128

Bens M, Vallet V, Cluzeaud F, Pascual-Letallec L, Kahn A, Rafestin-Oblin ME, Rossier BC, and Vandewalle A.Corticosteroid-dependent sodium transport in a novel immortalized mouse collecting duct principal cell line.J Am Soc Nephrol10: 923–934, 1999.

10.1152/ajprenal.00180.2004

10.1152/ajpcell.1996.271.1.C136

10.1074/jbc.271.32.19264

10.1097/01.ju.0000143882.52960.ee

10.1074/jbc.M005552200

10.1152/ajpheart.1998.275.1.H285

10.1172/JCI119352

10.1152/ajprenal.1997.273.2.F213

Harris RCand Breyer MD.Physiological regulation of cyclooxygenase-2 in the kidney.Am J Physiol Renal Physiol281: F1–F11, 2001.

10.1074/jbc.M111880200

10.1074/jbc.M212388200

10.1681/ASN.2004110930

10.1172/JCI117525

10.1172/JCI117525

10.1083/jcb.151.4.919

10.1074/jbc.270.18.10384

10.1159/000077593

10.1152/ajpcell.1994.266.1.C189

10.1152/ajpheart.1998.275.2.H400

10.1172/JCI117863

10.1172/JCI118628

Murillo-Carretero MI, Ilundain AA, and Echevarria M.Regulation of aquaporin mRNA expression in rat kidney by water intake.J Am Soc Nephrol10: 696–703, 1999.

10.1152/ajprenal.00291.2004

10.1073/pnas.92.4.1013

10.1073/pnas.90.24.11663

10.1152/physrev.00024.2001

Norregaard R, Jensen BL, Li C, Wang W, Knepper MA, Nielsen S, and Frokiaer J.COX-2 inhibition prevents downregulation of key renal water and sodium transport proteins in response to bilateral ureteral obstruction.Am J Physiol Renal Physiol289: F322–F333, 2005.

10.1128/MCB.21.15.4856-4867.2001

10.1172/JCI649

10.1128/MCB.25.1.389-402.2005

10.1152/ajprenal.2000.279.2.F370

10.1016/S0006-291X(03)00215-8

10.1074/jbc.273.6.3747

10.1152/ajprenal.1998.274.5.F978

10.1172/JCI119098

10.1152/ajprenal.0091.2001

10.1152/ajprenal.1996.271.2.F414

10.1111/j.1523-1755.2005.00071.x

10.1038/ki.1980.138

10.1172/JCI119312

10.1113/jphysiol.2001.012606

10.1152/ajprenal.2000.278.3.F388

10.1210/en.2003-0903

Thông tin
Thông tin xuất bản

American Journal of Physiology - Renal Physiology

Tập 290 Số 1

F177-F187

Thông tin tác giả