Nitric oxide and cGMP activate the Ras-MAP kinase pathway-stimulating protein tyrosine phosphorylation in rabbit aortic endothelial cells

Oliveira, Carlos Jorge Rocha; Schindler, Fernanda; Ventura, Armando Morais; Morais, Miriam S; Arai, Roberto Jun; Debbas, Victor; Stern, Arnold; Monteiro, Hugo P.

doi:10.1016/s0891-5849(03)00311-3

Cited by 92 publications

(49 citation statements)

References 33 publications

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“…This was further supported by our results showing that SNAP increased the ERK1/2 phosphorylation after 2 h of treatment, which was restored to control levels by PD-98059. Our results are in accordance with the studies of other investigators who showed that SNAP at 100 -300 M stimulated the ERK1/2 phosphorylation in various cell types including rabbit aortic endothelial cells (28,36). In addition, sodium nitroprusside, another donor of NO, was also shown to stimulate ERK1/2 phosphorylation in rat cardiomyocytes (24).…”

Section: Discussionsupporting

confidence: 93%

“…cAMP has been reported to modulate MAPK activity (36,45). Since SNAP treatment decreases the basal activity of adenylyl cyclase and results in decreased levels of cAMP, it may be possible that the decreased levels of cAMP induced by SNAP may be responsible for SNAP-evoked decreased ERK1/2 phosphorylation at 6 h and thereby decreased levels of G i ␣ proteins.…”

Section: Effect Of Odq Kt-5823 and Mntbap On Snap-induced Decreasedmentioning

confidence: 99%

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Nitric oxide attenuates the expression of natriuretic peptide receptor C and associated adenylyl cyclase signaling in aortic vascular smooth muscle cells: role of MAPK

Arejian

Li²,

Anand‐Srivastava³

2009

American Journal of Physiology-Heart and Circulatory Physiology

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Arejian M, Li Y, Anand-Srivastava MB. Nitric oxide attenuates the expression of natriuretic peptide receptor C and associated adenylyl cyclase signaling in aortic vascular smooth muscle cells: role of MAPK. Am J Physiol Heart Circ Physiol 296: H1859 -H1867, 2009. First published February 27, 2009 doi:10.1152/ajpheart.01108.2008We have earlier shown that the treatment of A10 vascular smooth muscle cells with S-nitroso-N-acetyl-penicillamine (SNAP); nitric oxide donor (NO) for 24 h decreased the expression of natriuretic peptide receptor C (NPR-C) and adenylyl cyclase signaling. The present study was undertaken to examine the implication of different signaling mechanisms in a NO-induced response. The treatment of A10 vascular smooth muscle cells with SNAP decreased the expression of NPR-C and Gi␣ proteins in a time-dependent manner. The expression of Gi␣ proteins was decreased at 6 h, whereas the expression of NPR-C was attenuated at 2 h. The NPR-C-mediated inhibition of adenylyl cyclase was attenuated (ϳ50%) after 2 h of treatment and was completely abolished after 6 h of treatment. The decreased expression of NPR-C and NPR-C-mediated attenuation of adenylyl cyclase after 2 h of treatment was reversed to control levels by PD-98059, a MEK inhibitor. SNAP also modulated the ERK1/2 phosphorylation in a time-dependent manner; an increase was observed up to 2 h, and, thereafter, the ERK1/2 phosphorylation was decreased. On the other hand, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and KT-5823 inhibitor of soluble guanylyl cyclase and protein kinase G, respectively, and Mn(III)tetrakis(4-benzoic acid)porphyrin, a scavenger of peroxynitrite, were unable to restore the SNAPinduced decreased expression of NPR-C protein and increased ERK1/2 phosphorylation to control levels. However, the decreased levels of phosphorylated ERK1/2 and Gi␣ proteins were restored to control levels by 8-bromo-cAMP. These results indicate that a temporal relationship follows between a NO-induced decreased expression of NPR-C and Gi␣ proteins. The decreased expression of NPR-C is mediated through cGMP-independent but MAPK-dependent pathway, whereas NO-induced decreased levels of cAMP may contribute to the decreased activation of MAPK and thereby decreased the expression of Gi␣ proteins. G proteins; mitogen-activated protein kinase NATRIURETIC PEPTIDES (NPs) are a family of three peptide hormones termed atrial NP (ANP), brain NP, and C-type NP, all of which are produced in mammalian hearts, including human hearts (31). ANP regulates a variety of physiological parameters, including blood pressure (7), by interacting with receptors on plasma membrane either to generate second messengers such as cAMP (2, 3) and cGMP (20,48) or to affect ion channels (7). Three types of NP receptors (NPRs) have been cloned; NPR-A (16) and NPR-B (15) subtypes are membranebound guanylate cyclases (130-180 kDa) that mediate the biological actions of NP through a regulation of intracellular cGMP levels (7), whereas NPR-C (4, 17) is a disulfide-bridged homodimer of 67-an...

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Section: Discussionsupporting

confidence: 93%

Section: Effect Of Odq Kt-5823 and Mntbap On Snap-induced Decreasedmentioning

confidence: 99%

Nitric oxide attenuates the expression of natriuretic peptide receptor C and associated adenylyl cyclase signaling in aortic vascular smooth muscle cells: role of MAPK

Arejian

Li²,

Anand‐Srivastava³

2009

American Journal of Physiology-Heart and Circulatory Physiology

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“…Previous studies exploring the relationship between NO and surfactant protein emphasized the role of toxic intermediates of NO such as peroxynitrite, methemoglobin, and NO 2 on the nitration of crucial tyrosine amino acids. However, in endothelial cell cultures, NO was shown to activate the Ras-ERK1/2 MAPK intracellular pathway, which stimulated protein tyrosine phosphorylation and led to the activation of transcription factors Myc and Elk1 (44,46).…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide decreases surfactant protein gene expression in primary cultures of type II pneumocytes

Lee

Gonzalez

Chapin

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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Inhaled nitric oxide (NO) is a selective pulmonary vasodilator effective in treating persistent pulmonary hypertension in newborns and in infants following congenital heart disease surgery. Recently, multiple in vivo and in vitro studies have shown a negative effect of NO on surfactant activity as well as surfactant protein gene expression. Although the relationship between NO and surfactant has been studied previously, the data has been hard to interpret due to the model systems used. The objective of the current study was to characterize the effect of NO on surfactant protein gene expression in primary rat type II pneumocytes cultured on a substratum that promoted the maintenance of type II cell phenotype. Exposure to a NO donor, S-nitroso-N-acetylpenicillamine (SNAP), decreased surfactant protein (SP)-A, (SP)-B, and (SP)-C mRNA levels in type II pneumocytes in a time-and dose-dependent manner. The effect was mediated in part by an increase in endothelin-1 secretion and a decrease in the intracellular messenger, phosphorylated ERK1/2 mitogen-activated protein kinases (MAPK). Exposing type II pneumocytes to endothelin-1 receptor antagonists PD-156707 or bosentan before exposure to SNAP partially prevented the decrease in surfactant protein gene expression. The results showed that NO mediated the decrease in surfactant protein gene expression at least in part through an increase in endothelin-1 secretion and a decrease in phosphorylated ERK1/2 MAPKs. extracellular signal-regulated kinase 1/2; endothelin-1 INHALED NITRIC OXIDE (NO) is a selective pulmonary vasodilator effective in treating elevated pulmonary vascular resistance in newborns with persistent pulmonary hypertension (10, 50) and in children with pulmonary hypertension following congenital heart disease (CHD) surgery (8, 43). However, multiple in vivo and in vitro studies have shown a negative effect of NO on surfactant activity as well as surfactant protein gene expression (26,58). In children with elevated pulmonary vascular resistance, any decrease in pulmonary compliance due to low surfactant activity can contribute to significant morbidity (13,31). Although the relationship between NO and surfactant has been studied, the model systems used previously included primary cultures that immediately begin to undergo dedifferentiation, whole animals, and alveolar epithelial cell lines that do not express the entire type II cell phenotype.Previous experiments exploring the role of NO on surfactant synthesis, secretion, and/or metabolism have focused on the role of toxic intermediates of NO such as peroxynitrite (25-26, 28, 42, 61), methemoglobin (29 -30, 32), and nitrogen dioxide (NO 2 ) (45). In vitro, peroxynitrite has been shown to decrease surfactant surface activity through lipid peroxidation and nitration of tyrosine residues on surfactant protein (SP)-A and SP-B (25-26, 28, 42, 61). Haddad et al. (27) also have shown that, in freshly isolated adult rat type II cells, several NO donors decreased the rate of surfactant synthesis as measured by the ...

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“…Subsequent studies have been done using isolated proteins inactivated with chemical NO donors. NO-mediated Ras activation has been shown to mediate signal transduction processes in cells including Raf 180 and Erk activation 181,182 leading to many different effects depending on the specific cells 180,[182][183][184][185] . It appears that Ras mutations do not normally occur in human hepatocellular carcinoma development 186 but it is quite clear that the Ras pathway is activated, however as evidenced by significantly enhanced Raf overexpression and enhanced activation 187,188 .…”

Section: Ras Pathway In Cancer Developmentmentioning

confidence: 99%

Nitric Oxide and Cancer Development

et al. 2007

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Abstract:The role of nitric oxide (NO) in cancer development has become a very active research area. This review presents an overview of many studies that implicate an important role of NO in the development of cancer. These include results in experimental models as well as many observations made on NO and inducible nitric oxide synthase (iNOS) in human cancers. Our survey of the literature has allowed us to conclude that in general large levels of NO will kill cancer cells but paradoxically at intermediate to lower levels NO prevents cancer cell apoptosis and enhances tumor growth. This basic tenet has been demonstrated in many experimental models. The mechanistic basis of how intermediate levels of NO mediate tumor development is an active area of research and is the subject of this review. NO mediated S-nitrosylation of key enzymes and regulatory proteins plays a critical role. Key proteins S-nitrosylated which enhance tumor development include several caspases involved in apoptosis, PTEN the tumor suppressor protein, Bcl-2 the mitochondrial protein which protects from apoptosis, OGG1 the DNA repair protein and methionine adenosyl transferase the liver protein which synthesizes adenosylmethionine. The S-nitrosylation of these proteins enhances DNA mutations, prevents cancer cell apoptosis and enhances oncogenic cell growth. (J Toxicol Pathol 2007; 20: 77-92)

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Nitric oxide and cGMP activate the Ras-MAP kinase pathway-stimulating protein tyrosine phosphorylation in rabbit aortic endothelial cells

Cited by 92 publications

References 33 publications

Nitric oxide attenuates the expression of natriuretic peptide receptor C and associated adenylyl cyclase signaling in aortic vascular smooth muscle cells: role of MAPK

Nitric oxide attenuates the expression of natriuretic peptide receptor C and associated adenylyl cyclase signaling in aortic vascular smooth muscle cells: role of MAPK

Nitric oxide decreases surfactant protein gene expression in primary cultures of type II pneumocytes

Nitric Oxide and Cancer Development

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