Friederich-Persson 2014 Adv Exp Med Biol
|Friederich-Persson M, Welch WJ, Luo Z, Palm F, Nordquist L (2014) Angiotensin II reduces transport-dependent oxygen consumption but increases transport-independent oxygen consumption in immortalized mouse proximal tubular cells. Adv Exp Med Biol 812:157-63.|
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 p22(phox); 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 p22(phox) which also displayed increased QO₂ at baseline. Transport-independent QO₂ was increased in p22(phox) 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 p22(phox). 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 p22(phox) 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 p22(phox), 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.
Labels: MiParea: Respiration, Genetic knockout;overexpression
Stress:Oxidative stress;RONS Organism: Mouse Tissue;cell: Kidney, Other cell lines