Whole-cell and nuclear NADPH oxidases levels and distribution in human endocardial endothelial, vascular smooth muscle, and vascular endothelial cells

Ahmarani, Lena; Avedanian, Levon; Al-Khoury, Johny; Perreault, Claudine; Jacques, Danielle; Bkaily, Ghassan

doi:10.1139/cjpp-2012-0265

Cited by 28 publications

(22 citation statements)

References 47 publications

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“…The pattern of immunohistochemical reactivity to NOX5 in pediatric ALK+ ALCL samples was faint and focal, displaying either a nuclear or cytoplasmic reactivity. These results are in line with a recent study demonstrating the presence of NOX5 in the cytosol and/or the nucleus in renal proximal tubule cells derived from patients with hypertension, in leukemia cells, endocardial and vascular endothelial cells, vascular smooth muscle cells, and in prostate cancer cells [20,[37][38][39]. The precise physiopathological significance of different NOX5 intracellular localization is currently unknown.…”

Section: Discussionsupporting

confidence: 93%

“…The precise physiopathological significance of different NOX5 intracellular localization is currently unknown. Nuclear ROS production might be involved in the modulation of mitogenic gene transcription, nuclear MAPK activation and/or nucleoplasmic calcium release from the nuclear Ttubule (NTT) system [39]. The characterization of the importance of nuclear NOX5-derived superoxide production in these processes was out of the scope of the current study but will constitute a worthy topic for further investigations.…”

Section: Discussionmentioning

confidence: 97%

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The NADPH oxidase NOX5 protects against apoptosis in ALK-positive anaplastic large-cell lymphoma cell lines

Carnesecchi

Rougemont²,

Doroshow

et al. 2015

Free Radical Biology and Medicine

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Reactive oxygen species (ROS) are key modulators of apoptosis and carcinogenesis. One of the important sources of ROS is NADPH oxidases (NOXs). The isoform NOX5 is highly expressed in lymphoid tissues, but it has not been detected in any common Hodgkin or non-Hodgkin lymphoma cell lines. In diverse, nonlymphoid malignant cells NOX5 exerts an antiapoptotic effect. Apoptosis suppression is the hallmark feature of a rare type of lymphoma, termed anaplastic lymphoma kinase-positive (ALK(+)) anaplastic large-cell lymphoma (ALCL), and a major factor in the therapy resistance and relapse of ALK(+) ALCL tumors. We applied RT-PCR and Western blot analysis to detect NOX5 expression in three ALK(+) ALCL cell lines (Karpas-299, SR-786, SUP-M2). We investigated the role of NOX5 in apoptosis by small-interfering RNA (siRNA)-mediated gene silencing and chemical inhibition of NOX5 using FACS analysis and examining caspase 3 cleavage in Karpas-299 cells. We used immunohistochemistry to detect NOX5 in ALK(+) ALCL pediatric tumors. NOX5 mRNA was uniquely detected in ALK(+) ALCL cells, whereas cell lines of other lymphoma classes were devoid of NOX5. Transfection of NOX5-specific siRNA and chemical inhibition of NOX5 abrogated calcium-induced superoxide production and increased caspase 3-mediated apoptosis in Karpas-299 cells. Immunohistochemistry revealed focal NOX5 reactivity in pediatric ALK(+) ALCL tumor cells. These results indicate that NOX5-derived ROS contribute to apoptosis blockage in ALK(+) ALCL cell lines and suggest NOX5 as a potential pharmaceutical target to enhance apoptosis and thus to suppress tumor progression and prevent relapse in pediatric ALK(+) ALCL patients that resist classical therapeutic approaches.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 97%

The NADPH oxidase NOX5 protects against apoptosis in ALK-positive anaplastic large-cell lymphoma cell lines

Carnesecchi

Rougemont²,

Doroshow

et al. 2015

Free Radical Biology and Medicine

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“…Nox1, Nox2, Nox3 and Nox4 are primarily associated with the cell membrane, in large part because of their obligatory need for cell membrane‐associated p22phox (Bedard & Krause, ; Maghzal et al., ). In contrast, NOX5 is expressed mainly in intracellular compartments localized mainly in the perinuclear area and ER (Ahmarani et al., ). The reason why NOX5 is abundant in these areas is unclear, but the ER is a site of protein synthesis and post‐translational modification.…”

Section: Regulation Of Nox5mentioning

confidence: 99%

NOX5: Molecular biology and pathophysiology

Touyz

Anagnostopoulou

Ríos

et al. 2019

Experimental Physiology

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New Findings What is the topic of this review? This review provides a comprehensive overview of Nox5 from basic biology to human disease and highlights unique features of this Nox isoform What advances does it highlight? Major advances in Nox5 biology relate to crystallization of the molecule and new insights into the pathophysiological role of Nox5. Recent discoveries have unravelled the crystal structure of Nox5, the first Nox isoform to be crystalized. This provides new opportunities to develop drugs or small molecules targeted to Nox5 in an isoform‐specific manner, possibly for therapeutic use. Moreover genome wide association studies (GWAS) identified Nox5 as a new blood pressure‐associated gene and studies in mice expressing human Nox5 in a cell‐specific manner have provided new information about the (patho) physiological role of Nox5 in the cardiovascular system and kidneys. Nox5 seems to be important in the regulation of vascular contraction and kidney function. In cardiovascular disease and diabetic nephropathy, Nox5 activity is increased and this is associated with increased production of reactive oxygen species and oxidative stress implicated in tissue damage. Abstract Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox), comprise seven family members (Nox1–Nox5 and dual oxidase 1 and 2) and are major producers of reactive oxygen species in mammalian cells. Reactive oxygen species are crucially involved in cell signalling and function. All Noxs share structural homology comprising six transmembrane domains with two haem‐binding regions and an NADPH‐binding region on the intracellular C‐terminus, whereas their regulatory systems, mechanisms of activation and tissue distribution differ. This explains the diverse function of Noxs. Of the Noxs, NOX5 is unique in that rodents lack the gene, it is regulated by Ca 2+ , it does not require NADPH oxidase subunits for its activation, and it is not glycosylated. NOX5 localizes in the perinuclear and endoplasmic reticulum regions of cells and traffics to the cell membrane upon activation. It is tightly regulated through numerous post‐translational modifications and is activated by vasoactive agents, growth factors and pro‐inflammatory cytokines. The exact pathophysiological significance of NOX5 remains unclear, but it seems to be important in the physiological regulation of sperm motility, vascular contraction and lymphocyte differentiation, and NOX5 hyperactivation has been implicated in cardiovascular disease, kidney injury and cancer. The field of NOX5 biology is still in its infancy, but with new insights into its biochemistry and cellular regulation, discovery of the NOX5 crystal structure and genome‐wide association studies implicating NOX5 in disease, the time is now ripe to advance NOX5 research. This review provides a comprehensive overview of our current understanding of NOX5, from basic ...

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“…24,40,41 Furthermore, the fact that in vivo treatment of SHRs with C-ANP 4-23 resulted in the attenuation of the enhanced production of O 2 − , NADPH oxidase activity, and NADPH oxidase subunits NOX4 and P 47phox suggests that C-ANP 4-23 -induced attenuation of high BP may also involve a reduction in oxidative stress. However, the implication of Nox5 that has been shown recently to be expressed in human endocardial cells, human VSMC, and human endothelial cells 42 in enhanced oxidative stress in VSMC from SHRs and its regulation by C-ANP [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] is not known and needs to be investigated. We earlier showed the implication of enhanced oxidative stress in the enhanced expression of Giα proteins in VSMC from SHR.…”

Section: Discussionmentioning

confidence: 99%

Natriuretic Peptide Receptor-C Attenuates Hypertension in Spontaneously Hypertensive Rats

Sarkar

Brochu

et al. 2014

Hypertension

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Abstract-C-Atrial natriuretic peptide (ANP) 4-23 , a ring deleted analog of ANP that specifically interacts with natriuretic peptide receptor-C (NPR-C), has been shown to decrease the enhanced expression of Giα proteins implicated in the pathogenesis of hypertension. In the present study, we investigated whether in vivo treatment of spontaneously hypertensive rats (SHRs) with C-ANP 4-23 could attenuate the development of high blood pressure (BP) and explored the underlying mechanisms responsible for this response. Intraperitoneal injection of C-ANP 4-23 at the concentration of 2 or 10 nmol/kg body weight to prehypertensive SHRs attenuated the development of high BP, and at 8 weeks it was decreased by ≈20 and 50 mm Hg, respectively; however, this treatment did not affect BP in Wistar-Kyoto rats. C-ANP 4-23 treatment of adult SHRs for 2 weeks also attenuated high BP, heart rate, and restored the impaired vasorelaxation toward control levels. In addition, the enhanced levels of superoxide anion (O 2 − ), peroxynitrite, NADPH oxidase activity, and the enhanced expression of Giα proteins, NOX4, p47 phox , nitrotyrosine, and decreased levels of endothelial nitric oxide synthase (eNOS or NOS3) and NO in SHRs were attenuated by C-ANP 4-23 treatment; however, the altered levels of NPR-A/NPR-C were not affected by this treatment. In conclusion, these results indicate that NPR-C activation by C-ANP 4-23 attenuates the development of high BP in SHRs through the inhibition of enhanced levels of Giα proteins and nitroxidative stress and not through eNOS/ cGMP pathway and suggest that NPR-C ligand may have the potential to be used as therapeutic agent in the treatment of Li et al NPR-C and Blood Pressure Regulation 847injection of pertussis toxin in prehypertensive rats (2-week-old SHRs) has been reported to prevent the development of BP,22 suggesting the implication of enhanced expression of Gi proteins in the pathogenesis of hypertension. C-ANP 4-23 that specifically interacts with NPR-C has been reported to decrease the levels of Giα proteins in A10 vascular smooth muscle cell (VSMC) 23 and in VSMC from SHRs. 24 In addition, C-ANP 4-23 was also shown to attenuate the enhanced oxidative stress in VSMC from SHRs 24 that contributes to the enhanced expression of Giα proteins in SHRs.25 Taken together, it may be possible that C-ANP 4-23 treatment of SHRs could also attenuate the high BP in SHRs. The present study was undertaken to investigate the effect of in vivo administration of C-ANP 4-23 on the development of high BP in SHRs. We have provided the first evidence that the treatment of prehypertensive SHRs with C-ANP 4-23 , an activator of NPR-C, attenuates the development of high BP in SHRs through the inhibition of enhanced expression of Gi proteins and oxidative stress.We have provided the first evidence that NPR-C activation by C-ANP 4-23 attenuates high BP through decreasing the enhanced oxidative stress and the augmented levels of Giα proteins. From these results it may be suggested that C-ANP [4][5][6][7][8][9][10][...

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Whole-cell and nuclear NADPH oxidases levels and distribution in human endocardial endothelial, vascular smooth muscle, and vascular endothelial cells

Cited by 28 publications

References 47 publications

The NADPH oxidase NOX5 protects against apoptosis in ALK-positive anaplastic large-cell lymphoma cell lines

The NADPH oxidase NOX5 protects against apoptosis in ALK-positive anaplastic large-cell lymphoma cell lines

NOX5: Molecular biology and pathophysiology

Natriuretic Peptide Receptor-C Attenuates Hypertension in Spontaneously Hypertensive Rats

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