Novel Nox homologues in the vasculature: focusing on Nox4 and Nox5

2010 ◽  
Vol 120 (4) ◽  
pp. 131-141 ◽  
Author(s):  
Augusto C. Montezano ◽  
Dylan Burger ◽  
Graziela S. Ceravolo ◽  
Hiba Yusuf ◽  
Maria Montero ◽  
...  

The Noxes (NADPH oxidases) are a family of ROS (reactive oxygen species)-generating enzymes. Of the seven family members, four have been identified as important sources of ROS in the vasculature: Nox1, Nox2, Nox4 and Nox5. Although Nox isoforms can be influenced by the same stimulus and co-localize in cellular compartments, their tissue distribution, subcellular regulation, requirement for cofactors and NADPH oxidase subunits and ability to generate specific ROS differ, which may help to understand the multiplicity of biological functions of these oxidases. Nox4 and Nox5 are the newest isoforms identified in the vasculature. Nox4 is the major isoform expressed in renal cells and appear to produce primarily H2O2. The Nox5 isoform produces ROS in response to increased levels of intracellular Ca2+ and does not require the other NADPH oxidase subunits for its activation. The present review focuses on these unique Noxes, Nox4 and Nox5, and provides novel concepts related to the regulation and interaction in the vasculature, and discusses new potential roles for these isoforms in vascular biology.

2006 ◽  
Vol 34 (5) ◽  
pp. 960-964 ◽  
Author(s):  
R. Dworakowski ◽  
N. Anilkumar ◽  
M. Zhang ◽  
A.M. Shah

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.


2004 ◽  
Vol 71 ◽  
pp. 85-96 ◽  
Author(s):  
Darren R. Ritsick ◽  
William A. Edens ◽  
James W. McCoy ◽  
J. David Lambeth

ROS (reactive oxygen species; including superoxide and H2O2) are conventionally thought of as being broadly reactive and cytotoxic. Phagocytes utilize an NADPH oxidase to generate large amounts of ROS, and exploit their toxic properties as a host-defence mechanism to kill invading microbes. However, the recent discovery of the Nox and Duox enzymes that are expressed in many non-phagocytic cells implies that the 'deliberate' generation of ROS has additional cellular roles, which are currently incompletely understood. Functions of ROS in mammals have been inferred primarily from cell-culture experiments, and include signalling for mitogenic growth, apoptosis and angiogenesis. Nox/Duox enzymes may also provide H2O2 as a substrate for peroxidase enzymes (or, in the case of Duox, for its own peroxidase domain), thereby supporting peroxidative reactions. A broad comparison of biological functions of ROS and Nox enzymes across species and kingdoms provides insights into possible functions in mammals. To further understand novel biological roles for Nox/Duox enzymes, we are manipulating the expression of Nox/Duox enzymes in model organisms including Caenorhabditis elegans, Drosophila melanogaster and mouse. This chapter focuses on new insights into the roles of Nox enzymes gained from these approaches.


2021 ◽  
Vol 22 (13) ◽  
pp. 7077
Author(s):  
Katarína Valachová ◽  
Ladislav Šoltés

Hyaluronan (HA) is a natural glycosaminoglycan present in many tissues of all vertebrates. HA has various biological functions, which are dependent on its molar mass. High-molar-mass HA has anti-angiogenic, immunosuppressive and anti-inflammatory properties, while low-molar-mass HA has opposite effects. HA has also antioxidative properties, however on the other hand it can be readily degraded by reactive oxygen species. For many years it has been used in treatment of osteoarthritis, cosmetics and in ophthalmology. In the last years there has been a growing interest of HA to also be applied in other fields of medicine such as skin wound healing, tissue engineering, dentistry and gene delivery. In this review we summarize information on modes of HA administration, properties and effects of HA in various fields of medicine including recent progress in the investigation of HA.


2021 ◽  
Vol 22 (12) ◽  
pp. 6320
Author(s):  
Monia Lenzi ◽  
Veronica Cocchi ◽  
Sofia Gasperini ◽  
Raffaella Arfè ◽  
Matteo Marti ◽  
...  

Mexedrone, α-PVP and α-PHP are synthetic cathinones. They can be considered amphetamine-like substances with a stimulating effect. Actually, studies showing their impact on DNA are totally absent. Therefore, in order to fill this gap, aim of the present work was to evaluate their mutagenicity on TK6 cells. On the basis of cytotoxicity and cytostasis results, we selected the concentrations (35–100 µM) to be used in the further analysis. We used the micronucleus (MN) as indicator of genetic damage and analyzed the MNi frequency fold increase by flow cytometry. Mexedrone demonstrated its mutagenic potential contrary to the other two compounds; we then proceeded by repeating the analyzes in the presence of extrinsic metabolic activation in order to check if it was possible to totally exclude the mutagenic capacity for α-PVP and α-PHP. The results demonstrated instead the mutagenicity of their metabolites. We then evaluated reactive oxygen species (ROS) induction as a possible mechanism at the basis of the highlighted effects but the results did not show a statistically significant increase in ROS levels for any of the tested substances. Anyway, our outcomes emphasize the importance of mutagenicity evaluation for a complete assessment of the risk associated with synthetic cathinones exposure.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Shan Chen ◽  
Xian-Fang Meng ◽  
Chun Zhang

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.


Planta ◽  
2014 ◽  
Vol 240 (5) ◽  
pp. 1023-1035 ◽  
Author(s):  
Jiangli Zhang ◽  
Changsheng Chen ◽  
Di Zhang ◽  
Houhua Li ◽  
Pengmin Li ◽  
...  

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