The Role of Gp91phox NADPH Oxidase during the Gestational Period of Mice

58 Recent studies suggest a crucial role of reactive oxygen species (ROS) for the signaling of Angiotensin II (Ang II) through type 1 Ang II receptor (AT1-R). However, the role of ROS in the regulation of AT1-R expression has not been explored. In this study, we examined the effect of an antioxidant on the homologous downregulation of AT1-R by Ang II. Ang II (10 -6 mol/L) decreased AT1-R mRNA with a peak suppression at 6 hours of stimulation in rat aortic vascular smooth muscle cells (VSMC). Ang II dose-dependently (10 -8 -10 -6 ) suppressed AT1-R mRNA at 6 hours of stimulation. Preincubation of VSMC with N-acetylcysteine (NAC), a potent antioxidant, almost completely inhibited the Ang II-induced downregulation of AT1-R mRNA. The effect of NAC was due to stabilization of the AT1-R mRNA that was destabilized by Ang II. Ang II did not affect the promoter activity of AT1-R gene. Diphenylene iodonium (DPI), an inhibitor of NADH/NADPH oxidase failed to inhibit the Ang II-induced AT1-R mRNA downregulation. The Ang II-induced AT1-R mRNA downregulation was also blocked by PD98059, an extracellular signal-regulated protein kinase (ERK) kinase inhibitor. Ang II-induced ERK activation was inhibited by NAC as well as PD98059 whereas DPI did not inhibit it. To confirm the role of ROS in the regulation of AT1-R mRNA expression, VSMC were stimulated with H 2 O 2 . H 2 O 2 suppressed the AT1-R mRNA expression and activated ERK. These results suggest that production of ROS and activation of ERK are critical for downregulation of AT1-R mRNA. The differential effect of NAC and DPI on the downregulation of AT1-R mRNA may suggest the presence of other sources than NADH/NADPH oxidase pathway for ROS in Ang II signaling. Generation of ROS through stimulation of AT1-R not only mediates signaling of Ang II but may play a crucial role in the adaptation process of AT1-R to the sustained stimulation of Ang II.

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NADPH Oxidase 4 Regulates Inflammation in Ischemic Heart Failure: Role of Soluble Epoxide Hydrolase

Antioxidants and Redox Signaling ◽

10.1089/ars.2018.7548 ◽

2019 ◽

Vol 31 (1) ◽

pp. 39-58 ◽

Cited By ~ 4

Author(s):

Mark D. Stevenson ◽

Chandrika Canugovi ◽

Aleksandr E. Vendrov ◽

Takayuki Hayami ◽

Dawn E. Bowles ◽

...

Keyword(s):

Heart Failure ◽

Nadph Oxidase ◽

Epoxide Hydrolase ◽

Soluble Epoxide Hydrolase ◽

Ischemic Heart ◽

Ischemic Heart Failure ◽

Nadph Oxidase 4

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Studying neuroprotective effect of Atorvastatin as a small molecule drug on high glucose-induced neurotoxicity in undifferentiated PC12 cells: role of NADPH oxidase

Metabolic Brain Disease ◽

10.1007/s11011-016-9883-1 ◽

2016 ◽

Vol 32 (1) ◽

pp. 41-49 ◽

Cited By ~ 2

Author(s):

Samira Rayegan ◽

Ahmad Reza Dehpour ◽

Ali Mohammad Sharifi

Keyword(s):

Nadph Oxidase ◽

Pc12 Cells ◽

Small Molecule ◽

High Glucose ◽

Neuroprotective Effect ◽

Small Molecule Drug

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NADPH Oxidase as a Therapeutic Target for Oxalate Induced Injury in Kidneys

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/462361 ◽

2013 ◽

Vol 2013 ◽

pp. 1-18 ◽

Cited By ~ 34

Author(s):

Sunil Joshi ◽

Ammon B. Peck ◽

Saeed R. Khan

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Nadph Oxidase ◽

Tissue Injury ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Reactive Oxygen ◽

Renal Tissue ◽

Oxygen Species ◽

Gene Expressions

A major role of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes is to catalyze the production of superoxides and other reactive oxygen species (ROS). These ROS, in turn, play a key role as messengers in cell signal transduction and cell cycling, but when they are produced in excess they can lead to oxidative stress (OS). Oxidative stress in the kidneys is now considered a major cause of renal injury and inflammation, giving rise to a variety of pathological disorders. In this review, we discuss the putative role of oxalate in producing oxidative stress via the production of reactive oxygen species by isoforms of NADPH oxidases expressed in different cellular locations of the kidneys. Most renal cells produce ROS, and recent data indicate a direct correlation between upregulated gene expressions of NADPH oxidase, ROS, and inflammation. Renal tissue expression of multiple NADPH oxidase isoforms most likely will impact the future use of different antioxidants and NADPH oxidase inhibitors to minimize OS and renal tissue injury in hyperoxaluria-induced kidney stone disease.

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