title: Aquaporin-2 promoter is synergistically regulated by nitric oxide and nuclear factor of activated T cells.
abstract: OBJECTIVE
  We have previously shown that aquaporin-2 (AQP2) is down-regulated in the renal medulla of rats made hypertensive by chronic inhibition of nitric oxide synthase. It has been shown that AQP2 expression is regulated by the calcineurin/nuclear factor of activated T cells (NFATc). Nitric oxide (NO) regulates the activity of NFATc via c-Jun-N-terminal kinase 2 (JNK2). Therefore, we hypothesized that increases in NO enhance NFATc-mediated up-regulation of AQP2 promoter activity.
  
  
  METHODS
  AQP2 mRNA and protein expression were detected in mouse renal papilla. AQP2 promoter luciferase reporter- and NFAT luciferase reporter-transfected MDCK cells were used to determine AQP2 promoter activity and NFATc activity, respectively. Cells were incubated with classic activators and inhibitors of NFATc and the NO pathway.
  
  
  RESULTS
  Our results demonstrate that both Ca(2+) and NO have a synergistic effect resulting in an increase in AQP2 mRNA and protein in mouse papilla and activation of the AQP2 promoter in kidney-derived cells. In addition, NO enhances Ca(2+)-induced NFATc activation. The underlying mechanism involves increased NFATc nuclear import and decreased export via protein kinase G-mediated inhibition of JNK1/2.
  
  
  CONCLUSIONS
  This is the first study defining novel regulatory roles for NO and NFATc in the control of AQP2, which is an important renal protein.
authors.affiliation: Biología Celular y Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: María F
authors.initials: MF
authors.lastname: Albertoni Borghese
authors.forename: Layne M
authors.initials: LM
authors.lastname: Bettini
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Nitta
authors.forename: Sergio
authors.initials: S
authors.lastname: de Frutos
authors.forename: Mónica
authors.initials: M
authors.lastname: Majowicz
authors.forename: Laura V
authors.initials: LV
authors.lastname: Gonzalez Bosc