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NADPH oxidase 1 deficiency alters caveolin phosphorylation and angiotensin II-receptor localization in vascular smooth muscle

Deffert-Delbouille, Christine
Ogier-Denis, Eric
Published in Antioxidants & Redox Signaling. 2009, vol. 11, no. 10, p. 2371-84
Abstract The superoxide-generating NADPH oxidase NOX1 is thought to be involved in signaling by the angiotensin II-receptor AT1R. However, underlying signaling steps are poorly understood. In this study, we investigated the effect of AngII on aortic smooth muscle from wild-type and NOX1-deficient mice. NOX1-deficient cells showed decreased basal ROS generation and did not produce ROS in response to AngII. Unexpectedly, AngII-dependent Ca(2+) signaling was markedly decreased in NOX1-deficient cells. Immunostaining demonstrated that AT1R was localized on the plasma membrane in wild-type, but intracellularly in NOX1-deficient cells. Immunohistochemistry and immunoblotting showed a decreased expression of AT1R in the aorta of NOX1-deficient mice. To investigate the basis of the abnormal AT1R targeting, we studied caveolin expression and phosphorylation. The amounts of total caveolin and of caveolae were not different in NOX1-deficient mice, but a marked decrease occurred in the phosphorylated form of caveolin. Exogenous H(2)O(2) or transfection of a NOX1 plasmid restored AngII responses in NOX1-deficient cells. Based on these findings, we propose that NOX1-derived reactive oxygen species regulate cell-surface expression of AT1R through mechanisms including caveolin phosphorylation. The lack cell-surface AT1R expression in smooth muscle could be involved in the decreased blood pressure in NOX1-deficient mice.
Keywords Angiotensin II/genetics/metabolismAnimalsAorta/anatomy & histologyCalcium/metabolismCaveolins/metabolismCells, CulturedMiceMice, Inbred C57BLMice, KnockoutMuscle, Smooth, Vascular/cytology/metabolismMyocytes, Smooth Muscle/cytology/metabolismNADH, NADPH Oxidoreductases/deficiency/geneticsPhosphorylationReactive Oxygen Species/metabolismReceptor, Angiotensin, Type 1/genetics/metabolismSignal Transduction/physiology
PMID: 19309260
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Research groups Groupe Schaller Karl Lothard (neurochirurgie) (851)
Obésité et syndrome métabolique (803)
Radicaux libres et cellules souches embryonnaires (60)
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BASSET, Olivier et al. NADPH oxidase 1 deficiency alters caveolin phosphorylation and angiotensin II-receptor localization in vascular smooth muscle. In: Antioxidants & redox signaling, 2009, vol. 11, n° 10, p. 2371-84. doi: 10.1089/ARS.2009.2584 https://archive-ouverte.unige.ch/unige:5405

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Deposited on : 2010-03-12

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