NADPH Oxidase Contributes to Angiotensin II Signaling in the Nucleus Tractus Solitarius

Wang, Gang; Anrather, Josef; Huang, Jie; Speth, Robert C.; Pickel, Virginia M.; Iadecola, Costantino

doi:10.1523/jneurosci.1176-04.2004

Cited by 157 publications

(199 citation statements)

References 67 publications

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“…Within dendrites, the major site of NADPH oxidase subunit immunolabeling in dmNTS neurons, p47 phox immunoreactivity was associated with intracellular organelles that are involved in protein transport and calcium signaling, particularly ER-like tubulovesicular organelles, which were frequently associated with the outer mitochondrial membrane. Thus, p47 phox immunolabeling in dendritic smooth ER, which are sites for calcium storage and release, is consistent with physiological evidence that calcium currents in dmNTS neurons are modulated by superoxide produced by NADPH oxidase (23,47,48). In addition to intracellular sites, p47 phox immunolabeling was also seen at synaptic and extra-synaptic areas of the plasmalemma, similar to other reports in the literature indicating that NADPH oxidase has a synaptic distribution in other brain regions (41).…”

Section: Dendritic P47 Phox Labeling In Dmnts Neurons Of Saline Adminsupporting

confidence: 90%

“…In the NTS, previous ultrastructural evidence indicates that NADPH oxidase subunits p47 phox, gp91 phox , and p22 phox are present in association with endomembranes, as well as the plasmalemma in neurons (16). In addition, previous neurophysiological results also indicate that functional NADPH oxidase potentiates AT-1A mediated calcium currents in dissociated second-order neurons in the dmNTS (47,48). The present results demonstrate that the subcellular distribution of p47 phox , and presumably functional NADPH oxidase-mediated superoxide production, is not spatially static, but subject to repartitioning in dendrites of dmNTS neurons in response to regimens of AngII or phenylephrine that produce a similar degree of hypertension.…”

Section: Repartitioning Of P47 Phox In Dendritic Profiles Of Dmnts Nementioning

confidence: 83%

“…This antiserum shows recognition of its epitope by Western Blotting, immunoprecipitation, and immunocytochemistry (Manufacturer's data). Preadsorption of each antisera with its respective blocking peptide prevented detection of immunolabeling (48). To label AT-1A receptors, we used an affinity purified rabbit anti-AT-1A receptor antiserum against the carboxy terminal peptide (amino acids 341-355), which was provided by Dr. Robert Speth (17,21).…”

Section: Antiseramentioning

confidence: 99%

“…NADPH oxidase was first described in phagocytes (24), but is also expressed in a wide range of cell-types (36,41,44), including NTS neurons (48). This enzyme consists of two membrane-bound subunits, gp91 phox and p22 phox , several mobile cytoplasmic subunits including, p40 phox , and p67 phox , and the essential p47 phox , as well as the small GTPase RAC (24,38).…”

Section: Introductionmentioning

confidence: 99%

“…In the dorsomedial NTS (dmNTS), an area that receives a high density of baroreceptors (9), the activation of AT-1A receptors produces a superoxide-dependent potentiation of calcium currents (47,48). In dmNTS, NADPH oxidase subunits are also present in membranous organelles in astroglia and dendritic processes of neurons (16).…”

Section: Introductionmentioning

confidence: 99%

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Changes in the subcellular distribution of NADPH oxidase subunit p47phox in dendrites of rat dorsomedial nucleus tractus solitarius neurons in response to chronic administration of hypertensive agents

Glass

Chan

Frys

et al. 2007

Experimental Neurology

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NADPH oxidase-generated superoxide can modulate crucial intracellular signaling cascades in neurons of the nucleus tractus solitarius (NTS), a brain region that plays an important role in cardiovascular processes. Modulation of NTS signaling by superoxide may be linked to the subcellular location of the mobile NADPH oxidase p47 phox subunit, which is known to be present in dendrites of NTS neurons. It is not known, however, if hypertension can produce changes in the trafficking of p47 phox in defined NTS subregions, particularly the preferentially barosensitive dorsomedial NTS (dmNTS), or preferentially gastrointestinal medial NTS (mNTS). We used immunogold electron microscopy to determine if p47 phox localization was differentially affected in dendritic profiles of neurons from these NTS subregions of the rat in response to distinct models of hypertension, namely chronic seven-day subcutaneous administration of angiotensin II (AngII), or phenylephrine. In small (<1 μm) dendritic processes, both AngII and phenylephrine produced a decrease in intracellular p47 phox labeling selectively in dmNTS neurons. In intermediate-size (1-2 μm) dendritic profiles in the dmNTS region only, there was an increase in p47 phox labeling in response to each hypertensive agent, although these changes occurred in different subcellular compartments. There was an increase in non-vesicular labeling in response to AngII, but an increase in surface labeling with phenylephrine. Moreover, each of the changes in p47 phox targeting mentioned above occurred in dendritic profiles with, or without immunoperoxidase labeling for the AngII AT-1A receptor subtype (AT-1A). These results indicate that chronic administration of agents that induce hypertension can also produce changes in the subcellular localization in p47 phox in dmNTS neurons. Thus, systemic hypertension may produce alterations in the trafficking of proteins associated with superoxide production in central autonomic neurons, thus revealing a potentially important neurogenic component of free radical production and systemic blood pressure elevation.

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Section: Dendritic P47 Phox Labeling In Dmnts Neurons Of Saline Adminsupporting

confidence: 90%

Section: Repartitioning Of P47 Phox In Dendritic Profiles Of Dmnts Nementioning

confidence: 83%

Section: Antiseramentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Changes in the subcellular distribution of NADPH oxidase subunit p47phox in dendrites of rat dorsomedial nucleus tractus solitarius neurons in response to chronic administration of hypertensive agents

Glass

Chan

Frys

et al. 2007

Experimental Neurology

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NADPH Oxidases: Structure and Function

Quinn¹

2013

Molecular Basis of Oxidative Stress

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Angiotensin‐converting enzyme inhibition reduces oxidative stress and protects dopaminergic neurons in a 6‐hydroxydopamine rat model of Parkinsonism

Lopez-Real

Rey

Soto‐Otero

et al. 2005

J of Neuroscience Research

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It is now established that the brain possesses a local renin-angiotensin system and that angiotensin II exerts multiple actions in the nervous system, including regulation of striatal dopamine release. Furthermore, angiotensin activates NADPH-dependent oxidases, which are a major source of superoxide, and angiotensin-converting enzyme inhibitors, commonly used in the treatment of hypertension and chronic heart failure, have shown antioxidant properties in several tissues. Oxidative stress is a key contributor to the pathogenesis and progression of Parkinson's disease. In the present study, we treated rats with intraventricular injections of the dopaminergic neurotoxin 6-hydroxydopamine and subcutaneous injections of the angiotensin-converting enzyme inhibitor Captopril to study the possible neuroprotective effect of the latter on the dopaminergic system and on 6-hydroxydopamine-induced oxidative stress. Rats treated with Captopril and 6-hydroxydopamine showed significantly less reduction in the number of dopaminergic neurons (i.e., immunoreactive to tyrosine hydroxylase) in the substantia nigra and in the density of striatal dopaminergic terminals than 6-hydroxydopamine-lesioned rats not treated with Captopril. In addition, Captopril reduced the levels of major oxidative stress indicators (i.e., lipid peroxidation and protein oxidation) in the ventral midbrain and the striatum of 6-hydroxydopamine-lesioned rats. Our results suggest that angiotensin-converting enzyme inhibitors may be useful for treatment of Parkinson's disease and that further investigation should focus on the neuroprotective capacity of these compounds.

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NADPH Oxidase Contributes to Angiotensin II Signaling in the Nucleus Tractus Solitarius

Cited by 157 publications

References 67 publications

Changes in the subcellular distribution of NADPH oxidase subunit p47phox in dendrites of rat dorsomedial nucleus tractus solitarius neurons in response to chronic administration of hypertensive agents

Changes in the subcellular distribution of NADPH oxidase subunit p47phox in dendrites of rat dorsomedial nucleus tractus solitarius neurons in response to chronic administration of hypertensive agents

NADPH Oxidases: Structure and Function

Angiotensin‐converting enzyme inhibition reduces oxidative stress and protects dopaminergic neurons in a 6‐hydroxydopamine rat model of Parkinsonism

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