Neuronal differentiation of NG108-15 cells has impact on nitric oxide- and membrane (natriuretic peptide receptor-A) cyclic GMP-generating proteins

Müller, Dieter; Greenland, Karen J.; Speth, Robert C.; Middendorff, Ralf

doi:10.1016/j.mce.2010.01.022

Cited by 10 publications

(6 citation statements)

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“…NG108 cells have neuronal properties, are immunoreactive to renin, and have angiotensin, angiotensinogen, angiotensin-converting enzyme as well as AT 1 and AT 2 receptor subtypes (8,20,39). These cells also have endogenous expression of nNOS (23,37,38) and NMDAR (3,18,25) and therefore serve as a suitable model for studying the interplay between receptors and gene expression at the cellular level in neurons (33,36).…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II-mediated posttranslational modification of nNOS in the PVN of rats with CHF: role for PIN

Sharma

Llewellyn

Zheng

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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An increased sympathetic drive is an adverse characteristic in chronic heart failure (CHF). The protein expression of neuronal nitric oxide synthase (nNOS)- and hence nitric oxide (NO)-mediated sympathoinhibition is reduced in the paraventricular nucleus (PVN) of rats with CHF. However, the molecular mechanism(s) of nNOS downregulation remain(s) unclear. The aim of the study was to reveal the underlying molecular mechanism for the downregulation of nNOS in the PVN of CHF rats. Sprague-Dawley rats with CHF (6-8 wk after coronary artery ligation) demonstrated decreased nNOS dimer/monomer ratio (42%), with a concomitant increase in the expression of PIN (a protein inhibitor of nNOS known to dissociate nNOS dimers into monomers) by 47% in the PVN. Similarly, PIN expression is increased in a neuronal cell line (NG108) treated with angiotensin II (ANG II). Furthermore, there is an increased accumulation of high-molecular-weight nNOS-ubiquitin (nNOS-Ub) conjugates in the PVN of CHF rats (29%). ANG II treatment in NG108 cells in the presence of a proteasome inhibitor, lactacystin, also leads to a 69% increase in accumulation of nNOS-Ub conjugates immunoprecipitated by an antiubiquitin antibody. There is an ANG II-driven, PIN-mediated decrease in the dimeric catalytically active nNOS in the PVN, due to ubiquitin-dependent proteolytic degradation in CHF. Our results show a novel intermediary mechanism that leads to decreased levels of active nNOS in the PVN, involved in subsequent reduction in sympathoinhibition during CHF, offering a new target for the treatment of CHF and other cardiovascular diseases.

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Section: Discussionmentioning

confidence: 99%

Angiotensin II-mediated posttranslational modification of nNOS in the PVN of rats with CHF: role for PIN

Sharma

Llewellyn

Zheng

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…2004). For GC‐A and GC‐B detection, blots were routinely incubated with blocking solution, then stripped (Müller et al. 2010) and re‐incubated with blocking solution prior to antibody exposure.…”

Section: Methodsmentioning

confidence: 99%

“…Goat anti-rabbit or anti-mouse IgG (Pierce, Rockford, IL, USA), linked to peroxidase, served as secondary antibodies, and signals were detected via enhanced chemiluminescence (Müller et al 2004). For GC-A and GC-B detection, blots were routinely incubated with blocking solution, then stripped (Müller et al 2010) and re-incubated with blocking solution prior to antibody exposure. This treatment was found to further reduce background staining of the blots, leading to enhanced resolution of specific immunoreactivity.…”

Section: Immunoblottingmentioning

confidence: 99%

The membrane receptors guanylyl cyclase‐A and ‐B undergo distinctive changes in post‐translational modification during brain development

Müller

Hildebrand

Lübberstedt

et al. 2010

Journal of Neurochemistry

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J. Neurochem. (2010) 115, 1024–1034. Abstract Temporal carbohydrate expression patterns at cell surfaces are thought to be of crucial regulatory significance during developmental processes. Hitherto, however, data on individual membrane proteins undergoing development‐associated changes in glycosylation are sparsely. Here, we show that the two natriuretic peptide receptors, guanylyl cyclase‐A (GC‐A) and GC‐B are subject to pronounced size alterations in the rat brain between postnatal day 1 and adult. Comparable size changes were not detectable for GC‐A and GC‐B in peripheral tissues and for three other membrane proteins (insulin receptor, insulin‐like growth factor‐II/mannose‐6‐phoshate receptor, neutral endopeptidase) in brain, indicating remarkable specificity. As revealed by treatments with carbohydrate‐digesting enzymes, both GC‐A and GC‐B are hyperglycosylated at N‐linked glycosylation sites in the developing brain. At postnatal day 1, the vast majority of GC‐B (but not GC‐A) molecules contain additionally an O‐linked carbohydrate modification of about 1 kDa in mass and a further modification of similar size which is resistant to enzymatic removal. The glycoforms exhibited functional activity in membrane GC assays, indicating proper folding and signaling capability. These data link recently reported roles of natriuretic peptides during brain development for the first time with specific glycosylation states of their cyclic GMP‐generating receptors.

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“…Indeed, in neuronal cell lines, observations with the selective AT 2 receptor agonist C21/M024 revealed that this production of NO induced by AT 2 was necessary for AT 2 -induced hyperpolarization of potassium channel function (Gao and Zucker, 2011). Production of NO following AT 2 receptor stimulation has been observed in various cell types, such as neuronal cells (Chaki and Inagami, 1993; Coté et al, 1998; Gendron et al, 2002; Zhao et al, 2003; Muller et al, 2010), vascular endothelial cells (Wiemer et al, 1993; Seyedi et al, 1995; Saito et al, 1996; Thorup et al, 1998; Baranov and Armstead, 2005) as well as in smooth muscle cells (de Godoy et al, 2004). It is already well accepted that AT 2 receptor activation plays an important role in the control of renal function particularly in chronic kidney diseases.…”

Section: Main Signaling Pathways Of the At2 Receptormentioning

confidence: 99%

How does angiotensin AT2 receptor activation help neuronal differentiation and improve neuronal pathological situations?

Guimond

Gallo‐Payet

2012

Front. Endocrin.

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The angiotensin type 2 (AT2) receptor of angiotensin II has long been thought to be limited to few tissues, with the primary effect of counteracting the angiotensin type 1 (AT1) receptor. Functional studies in neuronal cells have demonstrated AT2 receptor capability to modulate neuronal excitability, neurite elongation, and neuronal migration, suggesting that it may be an important regulator of brain functions. The observation that the AT2 receptor was expressed in brain areas implicated in learning and memory led to the hypothesis that it may also be implicated in cognitive functions. However, linking signaling pathways to physiological effects has always proven challenging since information relative to its physiological functions has mainly emerged from indirect observations, either from the blockade of the AT1 receptor or through the use of transgenic animals. From a mechanistic standpoint, the main intracellular pathways linked to AT2 receptor stimulation include modulation of phosphorylation by activation of kinases and phosphatases or the production of nitric oxide and cGMP, some of which are associated with the Gi-coupling protein. The receptor can also interact with other receptors, either G protein-coupled such as bradykinin, or growth factor receptors such as nerve growth factor or platelet-derived growth factor receptors. More recently, new advances have also led to identification of various partner proteins, thus providing new insights into this receptor’s mechanism of action. This review summarizes the recent advances regarding the signaling pathways induced by the AT2 receptor in neuronal cells, and discussed the potential therapeutic relevance of central actions of this enigmatic receptor. In particular, we highlight the possibility that selective AT2 receptor activation by non-peptide and selective agonists could represent new pharmacological tools that may help to improve impaired cognitive performance in Alzheimer’s disease and other neurological cognitive disorders.

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Neuronal differentiation of NG108-15 cells has impact on nitric oxide- and membrane (natriuretic peptide receptor-A) cyclic GMP-generating proteins

Cited by 10 publications

References 58 publications

Angiotensin II-mediated posttranslational modification of nNOS in the PVN of rats with CHF: role for PIN

Angiotensin II-mediated posttranslational modification of nNOS in the PVN of rats with CHF: role for PIN

The membrane receptors guanylyl cyclase‐A and ‐B undergo distinctive changes in post‐translational modification during brain development

How does angiotensin AT2 receptor activation help neuronal differentiation and improve neuronal pathological situations?

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