NADPH oxidases: key modulators in aging and age-related cardiovascular diseases?

Sahoo, Sanghamitra; Meijles, Daniel N.; Pagano, Patrick J.

doi:10.1042/cs20150087

Cited by 126 publications

(90 citation statements)

References 274 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3B). NADPH oxidase is one of the most important ROS producers within the cell (Sahoo, Meijles & Pagano, 2016). In our study, we determined that FAC affects expression of Nox4, which mainly mediates the clinical phenotype in bone loss-related diseases (Manolagas, 2010; Schröder, 2015).…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, the over-production ROS was paralleled with the increase of intracellular labile iron and the cytotoxicity of osteoblasts. The generation of ROS is tightly regulated through various ways, including NADPH oxidases, phagocyte oxidase and mitochondrial electron transport chain (Sahoo, Meijles & Pagano, 2016; Dikalov, 2011; Zhou et al, 2013). Emerging evidence indicates that NADPH oxidases are the primary generator of ROS in the skeletal system and Nox-derived ROS are key players which mediates osteoblasts dysfunction with osteoporosis (Manolagas, 2010; Schröder, 2015).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Iron overload induced death of osteoblasts in vitro: involvement of the mitochondrial apoptotic pathway

Tian

Dai

et al. 2016

PeerJ

View full text Add to dashboard Cite

BackgroundIron overload is recognized as a new pathogenfor osteoporosis. Various studies demonstrated that iron overload could induce apoptosis in osteoblasts and osteoporosis in vivo. However, the exact molecular mechanisms involved in the iron overload-mediated induction of apoptosis in osteoblasts has not been explored.PurposeIn this study, we attempted to determine whether the mitochondrial apoptotic pathway is involved in iron-induced osteoblastic cell death and to investigate the beneficial effect of N-acetyl-cysteine (NAC) in iron-induced cytotoxicity.MethodsThe MC3T3-E1 osteoblastic cell line was treated with various concentrations of ferric ion in the absence or presence of NAC, and intracellular iron, cell viability, reactive oxygen species, functionand morphology changes of mitochondria and mitochondrial apoptosis related key indicators were detected by commercial kits. In addition, to further explain potential mechanisms underlying iron overload-related osteoporosis, we also assessed cell viability, apoptosis, and osteogenic differentiation potential in bone marrow-derived mesenchymal stemcells(MSCs) by commercial kits.ResultsFerric ion demonstrated concentration-dependent cytotoxic effects on osteoblasts. After incubation with iron, an elevation of intracelluar labile iron levels and a concomitant over-generation of reactive oxygen species (ROS) were detected by flow cytometry in osteoblasts. Nox4 (NADPH oxidase 4), an important ROS producer, was also evaluated by western blot. Apoptosis, which was evaluated by Annexin V/propidium iodide staining, Hoechst 33258 staining, and the activation of caspase-3, was detected after exposure to iron. Iron contributed to the permeabilizatio of mitochondria, leading to the release of cytochrome C (cyto C), which, in turn, induced mitochondrial apoptosis in osteoblasts via activation of Caspase-3, up-regulation of Bax, and down-regulation of Bcl-2. NAC could reverse iron-mediated mitochondrial dysfunction and blocked the apoptotic events through inhibit the generation of ROS. In addition, iron could significantly promote apoptosis and suppress osteogenic differentiation and mineralization in bone marrow-derived MSCs.ConclusionsThese findings firstly demonstrate that the mitochondrial apoptotic pathway involved in iron-induced osteoblast apoptosis. NAC could relieved the oxidative stress and shielded osteoblasts from apoptosis casused by iron-overload. We also reveal that iron overload in bone marrow-derived MSCs results in increased apoptosis and the impairment of osteogenesis and mineralization.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Iron overload induced death of osteoblasts in vitro: involvement of the mitochondrial apoptotic pathway

Tian

Dai

et al. 2016

PeerJ

View full text Add to dashboard Cite

show abstract

“…Hemorrhage volume was not calculated by adding the areas of bleeding in all coronal brain slices in our study. In addition, NOX-generated ROS play a role in the development of age-related vascular diseases and are involved in the regulation of endothelial function with sex differences attributed to the differential expression of NOX isoforms 27 28. Whether the protective effects of NOX inhibition last beyond 24 h in young and aging rats of both sexes requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

NADPH oxidase inhibitor improves outcome of mechanical reperfusion by suppressing hemorrhagic transformation

Tuo

Zhong

Chen

et al. 2016

J NeuroIntervent Surg

View full text Add to dashboard Cite

show abstract

“…NADPH oxidases (NOX) are the major source of vascular ROS, including NOX1, NOX2, NOX4 and NOX5 [38]. Thus, we next analyzed the gene expression of NOX isoforms in HAEC stimulated with HG.…”

Section: Ellagic Acid Reduces Expression Of Nox4mentioning

confidence: 99%

Ellagic Acid Reduces High Glucose-Induced Vascular Oxidative Stress Through ERK1/2/NOX4 Signaling Pathway

Rozentsvit

Vinokur

Samuel

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Elevated production of reactive oxygen species (ROS) is linked to endothelial dysfunction and is one of the key contributors to the pathogenesis of diabetic vascular complications. Emerging evidence has indicated that ellagic acid (EA), a polyphenol found in fruits and nuts, possesses numerous biological activities including radical scavenging. However, whether EA exerts a vasculo-protective effect via antioxidant mechanisms in blood vessels exposed to diabetic conditions remains unknown. Accordingly, the goal of this current study was to determine whether EA decreases vascular ROS production and thus ameliorates endothelial dysfunction in the diabetic milieu. Methods: Intact rat aortas and human aortic endothelial cells (HAEC) were stimulated with 30mM high glucose (HG) with and without EA co-treatment. Endothelium-dependent vasodilation was measured using a wire myograph. Gene and protein expression of non-phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 4 (NOX4) were detected using RT-PCR and western blotting, respectively. Oxidative stress was determined by measuring ROS levels using dihydroethidium (DHE) staining. Results: Intact aortas exposed to HG condition displayed exacerbated ROS production and impairment of endothelium-dependent vasodilation, characterizing endothelial dysfunction. These effects were markedly reduced with EA treatment. HG enhanced ROS production in HAEC, paralleled by increased ERK1/2 activation and NOX4 expression. EA treatment blunted the increase of ROS generation, ERK1/2 activation and decreased NOX4. Conclusions: EA significantly decreases endothelial ROS levels and ameliorates the impairment of vascular relaxation induced by HG. Our results suggest that EA exerts a vasculo-protective effect under diabetic conditions via an antioxidant effect that involves inhibition of ERK1/2 and downregulation of NOX4.

show abstract

NADPH oxidases: key modulators in aging and age-related cardiovascular diseases?

Cited by 126 publications

References 274 publications

Iron overload induced death of osteoblasts in vitro: involvement of the mitochondrial apoptotic pathway

Iron overload induced death of osteoblasts in vitro: involvement of the mitochondrial apoptotic pathway

NADPH oxidase inhibitor improves outcome of mechanical reperfusion by suppressing hemorrhagic transformation

Ellagic Acid Reduces High Glucose-Induced Vascular Oxidative Stress Through ERK1/2/NOX4 Signaling Pathway

Contact Info

Product

Resources

About