Mitochondrial respiratory chain complex I is inactivated by NADPH oxidase Nox4

2013 ◽  
Vol 452 (2) ◽  
pp. 231-239 ◽  
Author(s):  
Rafał Kozieł ◽  
Haymo Pircher ◽  
Manuela Kratochwil ◽  
Barbara Lener ◽  
Martin Hermann ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Nadph Oxidase ◽  
Complex I ◽  
Chain Complex ◽  
Mitochondrial Morphology ◽  
Human Endothelial Cells ◽  
Native Page ◽  
Mitochondrial Respiratory Chain Complex ◽  
Permeabilized Cells ◽  
Nadph Oxidase 4

ROS (reactive oxygen species) generated by NADPH oxidases play an important role in cellular signal transduction regulating cell proliferation, survival and differentiation. Nox4 (NADPH oxidase 4) induces cellular senescence in human endothelial cells; however, intracellular targets for Nox4 remained elusive. In the present study, we show that Nox4 induces mitochondrial dysfunction in human endothelial cells. Nox4 depletion induced alterations in mitochondrial morphology, stabilized mitochondrial membrane potential and decreased production of H2O2 in mitochondria. High-resolution respirometry in permeabilized cells combined with native PAGE demonstrated that Nox4 specifically inhibits the activity of mitochondrial electron transport chain complex I, and this was associated with a decreased concentration of complex I subunits. These data suggest a new pathway by which sustained Nox4 activity decreases mitochondrial function.

NADPH oxidase 4 mediates upregulation of type 4 phosphodiesterases in human endothelial cells

2012 ◽  
Vol 227 (5) ◽  
pp. 1941-1950 ◽  
Author(s):  
Saima Muzaffar ◽  
Jamie Y. Jeremy ◽  
Gianni D. Angelini ◽  
Nilima Shukla
Keyword(s):  
Endothelial Cells ◽  
Nadph Oxidase ◽  
Human Endothelial Cells ◽  
Nadph Oxidase 4

963 Prostacyclin regulates NADPH oxidase 4 in human endothelial CELLS THEREBY promoting Cytoprotection

2012 ◽  
Vol 30 ◽  
pp. e278
Author(s):  
Hitesh M. Peshavariya ◽  
Guei-Sheung Liu ◽  
Catherine W.T. Chang ◽  
Fan Jiang ◽  
Elsa C. Chan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Nadph Oxidase ◽  
Human Endothelial Cells ◽  
Nadph Oxidase 4

scholarly journals Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy

2012 ◽  
Vol 302 (12) ◽  
pp. F1595-F1605 ◽  
Author(s):  
Isabel Mercedes García ◽  
Liliana Altamirano ◽  
Luciana Mazzei ◽  
Miguel Fornés ◽  
Marisa Nile Molina ◽  
...  
Keyword(s):  
Vitamin D ◽  
Nadph Oxidase ◽  
Protective Effect ◽  
Renin Angiotensin System ◽  
Obstructive Nephropathy ◽  
Control Group ◽  
Mitochondrial Morphology ◽  
Vitamin D Receptors ◽  
Nadph Oxidase 4 ◽  
Mitochondrial Fractions

Vitamin D slows the progression of chronic kidney disease. Furthermore, activators of vitamin D receptors (VDR) have suppressant effects on the renin-angiotensin system, as well as anti-inflammatory and antifibrotic actions. This study aimed to evaluate the cytoprotective effects of paricalcitol, a VDR activator, at the mitochondrial level using an obstructive nephropathy model [unilateral ureteral obstruction (UUO)]. Rats subjected to UUO and controls were treated daily with vehicle or paricalcitol. The control group underwent a sham surgery. The treatment was done for 15 days (30 ng/kg). The following were determined: biochemical parameters; fibrosis; apoptosis; mitochondrial morphology; VDR, AT1 receptor, and NADPH oxidase 4 expression; and NADPH oxidase activity (in total and in mitochondrial fractions from the renal cortex). VDR activation prevented fibrosis (20 ± 5 vs. 60 ± 10%) and the number of TUNEL-positive apoptotic cells (10 ± 3 vs. 25 ± 4) in UUO. Biochemical, histological, and molecular studies suggest mitochondrial injury. Electron microscopy revealed in UUO electronically luminous material in the nucleus. Some mitochondria were increased in size and contained dilated crests and larger than normal spaces in their interiors. These changes were not present with paricalcitol treatment. Additionally, high AT1-receptor mRNA and NADPH activity was reverted in mitochondrial fractions from obstructed paricalcitol-treated animals (0.58 ± 0.06 vs. 0.95 ± 0.05 relative densitometry units and 9,000 ± 800 vs. 15,000 ± 1,000 relative fluorescence units·μg protein−1·min−1, respectively). These changes were consistent with an improvement in VDR expression (0.75 ± 0.05 vs. 0.35 ± 0.04 relative densitometry units). These results suggest that paricalcitol confers a protective effect and reveal, as well, a possible AT1 receptor-dependent protective effect that occurs at the mitochondrial level.

scholarly journals Annexin Peptide Ac2-26 Suppresses TNFα-Induced Inflammatory Responses via Inhibition of Rac1-Dependent NADPH Oxidase in Human Endothelial Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e60790 ◽  
Author(s):  
Hitesh M. Peshavariya ◽  
Caroline J. Taylor ◽  
Celeste Goh ◽  
Guei-Sheung Liu ◽  
Fan Jiang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Nadph Oxidase ◽  
Inflammatory Responses ◽  
Human Endothelial Cells
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