Angiotensin II Reduces Transport-Dependent Oxygen Consumption but Increases Transport-Independent Oxygen Consumption in Immortalized Mouse Proximal Tubular Cells

  • Malou Friederich-Persson
  • William J. Welch
  • Zaiming Luo
  • Fredrik Palm
  • Lina Nordquist
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 812)

Abstract

Oxidative stress is closely associated with renal dysfunction following diabetes and hypertension. Angiotensin II (Ang II) can activate the NADPH-oxidase, increasing oxidative stress that is thought to blunt proximal tubular electrolyte transport and thereby oxygen consumption (QO2). We investigated the effect of Ang II on QO2 in immortalized mouse proximal tubular cells over-expressing the NADPH oxidase subunit p22phox; a model of increased oxidative stress. Cultured cells were exposed to either Ang II or H2O2 for 48 h. QO2 was determined during baseline (113 mmol/l NaCl; transport-dependent QO2) and during sodium-free conditions (transport-independent QO2). Ang II reduced transport-dependent QO2 in wild-types, but not in p22phox which also displayed increased QO2 at baseline. Transport-independent QO2 was increased in p22phox and Ang II had no additional effect, whereas it increased QO2 in wild-type. Addition of H2O2 reduced transport-dependent QO2 in wild-types, but not in p22phox. Transport-independent QO2 was unaffected by H2O2. The similar effects of Ang II and H2O2 to reduce transport-dependent QO2 suggest a direct regulatory role of oxidative stress. In accordance, the transport-dependent QO2 was reduced in p22phox already during baseline. The effects of Ang II on transport-independent QO2 was not replicated by H2O2, indicating direct regulation via Ang II-receptors independently of oxidative stress. However, the Ang II effect was absent in p22phox, suggesting that oxidative stress also modulates normal Ang II signaling. In conclusion, Ang II affects both transport-dependent and transport-independent QO2 in proximal tubular cells and may be an important pathway modulating renal QO2.

Keywords

Proximal tubule cell Oxidative stress Angiotensin-II Oxygen consumption Electrolyte transport 

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Copyright information

© Springer Science+Business Media, LLC 2014

Authors and Affiliations

  • Malou Friederich-Persson
    • 1
  • William J. Welch
    • 2
  • Zaiming Luo
    • 2
  • Fredrik Palm
    • 1
    • 3
    • 4
  • Lina Nordquist
    • 5
  1. 1.Department of Medical Cell BiologyUppsala University, Biomedical CenterUppsalaSweden
  2. 2.Department of MedicineGeorgetown University Medical CenterWashington DCUSA
  3. 3.Department of Medical and Health SciencesLinköping UniversityLinköpingSweden
  4. 4.Center for Medical Image Science and VisualizationLinköping UniversityLinköpingSweden
  5. 5.Department of Medical Cell BiologyUppsala UniversityUppsalaSweden

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