Aldosterone increases kidney tubule cell oxidants through calcium-mediated activation of NADPH oxidase and nitric oxide synthase

Nina Queisser, Nicole Schupp, Helga Stopper, Reinhard Schinzel, Patricia I. Oteiza

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Chronic hyperaldosteronism has been associated with an increased cancer risk. We recently showed that aldosterone causes an increase in cell oxidants, DNA damage, and NF-κB activation. This study investigated the mechanisms underlying aldosterone-induced increase in cell oxidants in kidney tubule cells. Aldosterone caused an increase in both reactive oxygen and reactive nitrogen (RNS) species. The involvement of the activation of NADPH oxidase in the increase in cellular oxidants was demonstrated by the inhibitory action of the NADPH oxidase inhibitors DPI, apocynin, and VAS2870 and by the migration of the p47 subunit to the membrane. NADPH oxidase activation occurred as a consequence of an increase in cellular calcium levels and was mediated by protein kinase C. The prevention of RNS increase by BAPTA-AM, W-7, and L-NAME indicates a calcium-calmodulin activation of NOS. A similar pattern of effects of the NADPH oxidase and NOS inhibitors was observed for aldosterone-induced DNA damage and NF-κB activation, both central to the pathogenesis of chronic aldosteronism. In summary, this paper demonstrates that aldosterone, via the mineralocorticoid receptor, causes an increase in kidney cell oxidants, DNA damage, and NF-κB activation through a calcium-mediated activation of NADPH oxidase and NOS. Therapies targeting calcium, NOS, and NADPH oxidase could prevent the adverse effects of hyperaldosteronism on kidney function as well as its potential oncogenic action.

Original languageEnglish (US)
Pages (from-to)1996-2006
Number of pages11
JournalFree Radical Biology and Medicine
Volume51
Issue number11
DOIs
StatePublished - Dec 1 2011

Fingerprint

Kidney Tubules
NADPH Oxidase
Aldosterone
Oxidants
Nitric Oxide Synthase
Chemical activation
Calcium
Hyperaldosteronism
DNA Damage
DNA
Kidney
Reactive Nitrogen Species
Mineralocorticoid Receptors
NG-Nitroarginine Methyl Ester
Calmodulin
Protein Kinase C
Action Potentials
Oxygen
Membranes
Neoplasms

Keywords

  • Aldosterone
  • Calcium
  • DNA damage
  • Free radicals
  • Kidney
  • NADPH oxidase
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Aldosterone increases kidney tubule cell oxidants through calcium-mediated activation of NADPH oxidase and nitric oxide synthase. / Queisser, Nina; Schupp, Nicole; Stopper, Helga; Schinzel, Reinhard; Oteiza, Patricia I.

In: Free Radical Biology and Medicine, Vol. 51, No. 11, 01.12.2011, p. 1996-2006.

Research output: Contribution to journalArticle

Queisser, Nina ; Schupp, Nicole ; Stopper, Helga ; Schinzel, Reinhard ; Oteiza, Patricia I. / Aldosterone increases kidney tubule cell oxidants through calcium-mediated activation of NADPH oxidase and nitric oxide synthase. In: Free Radical Biology and Medicine. 2011 ; Vol. 51, No. 11. pp. 1996-2006.
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