Nox5 and the Regulation of Cellular Function

Fulton, David

doi:10.1089/ars.2009.2587

Cited by 134 publications

(145 citation statements)

References 78 publications

Supporting

Mentioning

142

Contrasting

Unclassified

Order By: Relevance

“…In blood vessels from individuals without coronary artery disease, NOX5 expression is very low, but it is substantially increased in blood vessels of individuals with the disease (24). In this study, we found that NOX5 promoter hypermethylation occurred more often in VSD myocardial tissue by methylationspecific PCR.…”

Section: Discussionsupporting

confidence: 47%

DNA hypermethylation of the NOX5 gene in fetal ventricular septal defect

Zhu

Chen

et al. 2011

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Ventricular septal defect (VSD) is the most comon form of congenital heart disease (CHD). DNA hypermethylation analysis may provide an insight into the molecular features and pathogenesis of this heart disease. Although aberrant DNA hypermethylation is implicated in the pathophysiology of this heart disease, only a limited number of genes are known to be epigenetically altered in VSD. We previously identified regulation of the NOX5 gene by hypermethylation in VSD fetuses by promoter methylation microarrays. This study was designed to detect the expression of NOX5 mRNA in VSD and normal fetuses. We also verified the results of promoter methylation microarrays by methylation-specific PCR. DNA extraction and nested methylation-specific PCR were performed on myocardial tissue samples from 21 VSD and 15 normal fetuses. The primers specific for methylated vs. unmethylated DNA were designed and amplified by nested PCR. The products were visualized on agarose gel. Hypermethylation of the NOX5 promoter was more frequent in VSD fetuses (66.67%) than in normal fetuses (20%). There was a significant concordance between NOX5 methylation and a decrease in its mRNA expression. Taken together, our results demonstrate that hypermethylation of the NOX5 gene may be involved in the pathogenesis of VSD.

show abstract

Section: Discussionsupporting

confidence: 47%

DNA hypermethylation of the NOX5 gene in fetal ventricular septal defect

Zhu

Chen

et al. 2011

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…We verified that ET-1 increased ROS levels and activated ERK1/2 in PASMCs and that increased [Ca 2ϩ ] i was necessary for both responses. Ca 2ϩ -dependent ROS generation may be due to the action of NADPH oxidase (Nox) (18,28), since ROS generation was inhibited by the Nox inhibitor DPI; however, DPI binds nonspecifically to flavins and also inhibits other oxidases. The activation of ERK1/2 depended on increased ROS levels, since antioxidants blocked ET-1-dependent ERK1/2 activation.…”

Section: Discussionmentioning

confidence: 99%

Activation of hypoxia-inducible factor-1 in pulmonary arterial smooth muscle cells by endothelin-1

Pisarcik

Maylor

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Pisarcik S, Maylor J, Lu W, Yun X, Undem C, Sylvester JT, Semenza GL, Shimoda LA. Activation of hypoxia-inducible factor-1 in pulmonary arterial smooth muscle cells by endothelin-1. Am J Physiol Lung Cell Mol Physiol 304: L549 -L561, 2013. First published February 15, 2013 doi:10.1152/ajplung.00081.2012.-Numerous cellular responses to hypoxia are mediated by the transcription factor hypoxia-inducible factor-1 (HIF-1). HIF-1 plays a central role in the pathogenesis of hypoxic pulmonary hypertension. Under certain conditions, HIF-1 may utilize feedforward mechanisms to amplify its activity. Since hypoxia increases endothelin-1 (ET-1) levels in the lung, we hypothesized that during moderate, prolonged hypoxia ET-1 might contribute to HIF-1 signaling in pulmonary arterial smooth muscle cells (PASMCs). Primary cultures of rat PASMCs were treated with ET-1 or exposed to moderate, prolonged hypoxia (4% O2 for 60 h). Levels of the oxygen-sensitive HIF-1␣ subunit and expression of HIF target genes were increased in both hypoxic cells and cells treated with ET-1. Both hypoxia and ET-1 also increased HIF-1␣ mRNA expression and decreased mRNA and protein expression of prolyl hydroxylase 2 (PHD2), which is the protein responsible for targeting HIF-1␣ for O2-dependent degradation. The induction of HIF-1␣ by moderate, prolonged hypoxia was blocked by BQ-123, an antagonist of ET-1 receptor subtype A. The effects of ET-1 were mediated by increased intracellular calcium, generation of reactive oxygen species, and ERK1/2 activation. Neither ET-1 nor moderate hypoxia induced the expression of HIF-1␣ or HIF target genes in aortic smooth muscle cells. These results suggest that ET-1 induces a PASMC-specific increase in HIF-1␣ levels by upregulation of HIF-1␣ synthesis and downregulation of PHD2-mediated degradation, thereby amplifying the induction of HIF-1␣ in PASMCs during moderate, prolonged hypoxia. calcium; prolyl hydroxylase; pulmonary hypertension IN A VARIETY OF CHRONIC lung diseases, the pulmonary circulation is exposed to prolonged periods of hypoxia, often resulting in the development of pulmonary hypertension. Numerous studies have described the structural and functional changes that occur in the pulmonary circulation in response to chronic hypoxia (60). Structural remodeling, characterized by pulmonary arterial smooth muscle cell (PASMC) proliferation, intimal thickening, and extension of muscle into previously nonmuscular arterioles, is commonly observed with pulmonary hypertension (23,40). Changes in the vascular wall are accompanied by active contraction of vessels, evidenced by acute reduction in pulmonary arterial pressure in response to vasodilatory agents (42, 44). These pulmonary vascular changes result, in large part, from altered expression of genes encoding ion channels and transporters that control PASMC ion homeostasis, including increased expression of Na ϩ /H ϩ exchanger isoform 1 (NHE1) and the canonical transient receptor potential (TRPC) family members TRPC1 and TRPC6, as well as reduced levels of mRNA...

show abstract

“…Nox5 is the most recently identified Nox and is unique: It is Ca 2 + sensitive, possesses a calmodulin-like domain with Ca 2 + binding sites, and does not require any Nox subunits for its activity (62,92,138,185). Nox5 was first identified in testes and spleen and, more recently, in vascular cells.…”

Section: Nox5mentioning

confidence: 99%

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

Montezano

Touyz²

2014

Antioxidants & Redox Signaling

232

177

View full text Add to dashboard Cite

Significance: Reactive oxygen species (ROS) are signaling molecules that are important in physiological processes, including host defense, aging, and cellular homeostasis. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in the onset and/or progression of chronic diseases, including hypertension. Recent Advances: Although oxidative stress may not be the only cause of hypertension, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors, such as salt loading, activation of the renin-angiotensin-aldosterone system, and sympathetic hyperactivity, at least in experimental models. A major source for ROS in the cardiovascular-renal system is a family of nicotinamide adenine dinucleotide phosphate oxidases (Noxs), including the prototypic Nox2-based Nox, and Nox family members: Nox1, Nox4, and Nox5. Critical Issues: Although extensive experimental data support a role for increased ROS levels and altered redox signaling in the pathogenesis of hypertension, the role in clinical hypertension is unclear, as a direct causative role of ROS in blood pressure elevation has yet to be demonstrated in humans. Nevertheless, what is becoming increasingly evident is that abnormal ROS regulation and aberrant signaling through redoxsensitive pathways are important in the pathophysiological processes which is associated with vascular injury and target-organ damage in hypertension. Future Directions: There is a paucity of clinical information related to the mechanisms of oxidative stress and blood pressure elevation, and a few assays accurately measure ROS directly in patients. Such further ROS research is needed in humans and in the development of adequately validated analytical methods to accurately assess oxidative stress in the clinic. Antioxid. Redox Signal. 20,[164][165][166][167][168][169][170][171][172][173][174][175][176][177][178][179][180][181][182]

show abstract

Nox5 and the Regulation of Cellular Function

Cited by 134 publications

References 78 publications

DNA hypermethylation of the NOX5 gene in fetal ventricular septal defect

DNA hypermethylation of the NOX5 gene in fetal ventricular septal defect

Activation of hypoxia-inducible factor-1 in pulmonary arterial smooth muscle cells by endothelin-1

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

Contact Info

Product

Resources

About