Redox signalling involving NADPH oxidase-derived reactive oxygen species

Increased oxidative stress plays an important role in the pathophysiology of many diseases such as atherosclerosis, diabetes mellitus, myocardial infarction and heart failure. In addition to the well-known damaging effects of oxygen-free radicals, ROS (reactive oxygen species) also have signalling roles, acting as second messengers that modulate the activity of diverse intracellular signalling pathways and transcription factors, thereby inducing changes in cell phenotype. NADPH oxidases appear to be especially important sources of ROS involved in redox signalling. Seven NADPH oxidase isoforms, known as Noxs (NAPDH oxidases), are expressed in a cell- and tissue-specific fashion. These oxidases are thought to subserve distinct functions as a result of their tightly regulated activation (e.g. by neurohormonal and growth factors and mechanical stimuli) and their specific coupling with distinct downstream signalling pathways. In the present paper, we review the structure and mechanisms of activation of NADPH oxidases and consider their involvement in redox signalling, focusing mainly on the cardiovascular system.

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Faculty Opinions recommendation of Nox4 is a protective reactive oxygen species generating vascular NADPH oxidase.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.716297801.791652853 ◽

2012 ◽

Author(s):

Martin A Schwartz

Keyword(s):

Reactive Oxygen Species ◽

Nadph Oxidase ◽

Reactive Oxygen ◽

Oxygen Species

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Reactive Oxygen Species: Beyond Their Reactive Behavior

Neurochemical Research ◽

10.1007/s11064-020-03208-7 ◽

2021 ◽

Vol 46 (1) ◽

pp. 77-87

Author(s):

Arnaud Tauffenberger ◽

Pierre J. Magistretti

Keyword(s):

Reactive Oxygen Species ◽

Second Messengers ◽

Critical Role ◽

Complex Function ◽

Reactive Oxygen ◽

High Reactivity ◽

Oxygen Species ◽

Health And Disease ◽

Cellular Dysfunction ◽

The Brain

AbstractCellular homeostasis plays a critical role in how an organism will develop and age. Disruption of this fragile equilibrium is often associated with health degradation and ultimately, death. Reactive oxygen species (ROS) have been closely associated with health decline and neurological disorders, such as Alzheimer’s disease or Parkinson’s disease. ROS were first identified as by-products of the cellular activity, mainly mitochondrial respiration, and their high reactivity is linked to a disruption of macromolecules such as proteins, lipids and DNA. More recent research suggests more complex function of ROS, reaching far beyond the cellular dysfunction. ROS are active actors in most of the signaling cascades involved in cell development, proliferation and survival, constituting important second messengers. In the brain, their impact on neurons and astrocytes has been associated with synaptic plasticity and neuron survival. This review provides an overview of ROS function in cell signaling in the context of aging and degeneration in the brain and guarding the fragile balance between health and disease.

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Thioredoxin-interacting Protein Mediates High Glucose-induced Reactive Oxygen Species Generation by Mitochondria and the NADPH Oxidase, Nox4, in Mesangial Cells

Journal of Biological Chemistry ◽

10.1074/jbc.m112.419101 ◽

2013 ◽

Vol 288 (10) ◽

pp. 6835-6848 ◽

Cited By ~ 95

Author(s):

Anu Shah ◽

Ling Xia ◽

Howard Goldberg ◽

Ken W. Lee ◽

Susan E. Quaggin ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Nadph Oxidase ◽

High Glucose ◽

Mesangial Cells ◽

Reactive Oxygen Species Generation ◽

Reactive Oxygen ◽

Oxygen Species ◽

Interacting Protein ◽

Thioredoxin Interacting Protein

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Role of NADPH Oxidase-Mediated Reactive Oxygen Species in Podocyte Injury

BioMed Research International ◽

10.1155/2013/839761 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 47

Author(s):

Shan Chen ◽

Xian-Fang Meng ◽

Chun Zhang

Keyword(s):

Reactive Oxygen Species ◽

Nadph Oxidase ◽

Epithelial To Mesenchymal Transition ◽

Kidney Diseases ◽

Treatment Strategies ◽

Reactive Oxygen ◽

Glomerular Sclerosis ◽

Oxygen Species ◽

Podocyte Injury ◽

Mesenchymal Transition

Proteinuria is an independent risk factor for end-stage renal disease (ESRD) (Shankland, 2006). Recent studies highlighted the mechanisms of podocyte injury and implications for potential treatment strategies in proteinuric kidney diseases (Zhang et al., 2012). Reactive oxygen species (ROS) are cellular signals which are closely associated with the development and progression of glomerular sclerosis. NADPH oxidase is a district enzymatic source of cellular ROS production and prominently expressed in podocytes (Zhang et al., 2010). In the last decade, it has become evident that NADPH oxidase-derived ROS overproduction is a key trigger of podocyte injury, such as renin-angiotensin-aldosterone system activation (Whaley-Connell et al., 2006), epithelial-to-mesenchymal transition (Zhang et al., 2011), and inflammatory priming (Abais et al., 2013). This review focuses on the mechanism of NADPH oxidase-mediated ROS in podocyte injury under different pathophysiological conditions. In addition, we also reviewed the therapeutic perspectives of NADPH oxidase in kidney diseases related to podocyte injury.

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