Regulation of Nitric Oxide-Sensitive Guanylyl Cyclase

Friebe, Andreas; Koesling, Doris

doi:10.1161/01.res.0000082524.34487.31

Cited by 460 publications

(330 citation statements)

References 144 publications

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“…RBF or E2F proteins themselves are potential direct targets for NO action, for example, via S-nitrosylation of cysteine residues by endogenous NO or NO donors (Stamler et al 2001); intriguingly, Rb is one of the several proteins identified in an in vivo screen for S-nitrosylated proteins in mammalian cells (Jaffrey et al 2001). Furthermore, the effects of NO may also be mediated by cGMP signaling, as guanylate cyclase is a crucial direct target of NO in many systems (Ignarro 2000;Russwurm and Koesling 2002) and activated cGMP-phosphodiesterases can serve as an effective counterbalance to the NO signal (Broderick et al 2003;Friebe and Koesling 2003;Mullershausen et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Regulation of multimers via truncated isoforms: a novel mechanism to control nitric-oxide signaling

Stasiv

Kuzin²,

Regulski³

et al. 2004

Genes Dev.

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Nitric oxide (NO) is an essential regulator of Drosophila development and physiology. We describe a novel mode of regulation of NO synthase (NOS) function that uses endogenously produced truncated protein isoforms of Drosophila NOS (DNOS). These isoforms inhibit NOS enzymatic activity in vitro and in vivo, reflecting their ability to form complexes with the full-length DNOS protein (DNOS1). Truncated isoforms suppress the antiproliferative action of DNOS1 in the eye imaginal disc by impacting the retinoblastoma-dependent pathway, yielding hyperproliferative phenotypes in pupae and adult flies. Our results indicate that endogenous products of the dNOS locus act as dominant negative regulators of NOS activity during Drosophila development.

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Section: Discussionmentioning

confidence: 99%

Regulation of multimers via truncated isoforms: a novel mechanism to control nitric-oxide signaling

Stasiv

Kuzin²,

Regulski³

et al. 2004

Genes Dev.

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“…NO stimulates cGMP production by activating soluble guanylate cyclases [29]. Therefore, we exposed A549 cells to NO-Cbi for different times; additionally some cells were treated with the PDE V inhibitor vardenafil.…”

Section: No-cbi Positively Affects Wound Closure Through a Cgmp-depenmentioning

confidence: 99%

Nitrosyl-cobinamide (NO-Cbi), a new nitric oxide donor, improves wound healing through cGMP/cGMP-dependent protein kinase

Spitler

Schwappacher

et al. 2013

Cellular Signalling

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a b s t r a c t a r t i c l e i n f oNitric oxide (NO) donors have been shown to improve wound healing, but the mechanism is not well defined. Here we show that the novel NO donor nitrosyl-cobinamide (NO-Cbi) improved in vitro wound healing in several cell types, including an established line of lung epithelial cells and primary human lung fibroblasts. On a molar basis, NO-Cbi was more effective than two other NO donors, with the effective NO-Cbi concentration ranging from 3 to 10 μM, depending on the cell type. Improved wound healing was secondary to increased cell migration and not cell proliferation. The wound healing effect of NO-Cbi was mediated by cGMP, mainly through cGMPdependent protein kinase type I (PKGI), as determined using pharmacological inhibitors and activators, and siRNAs targeting PKG type I and II. Moreover, we found that Src and ERK were two downstream mediators of NO-Cbi's effect. We conclude that NO-Cbi is a potent inducer of cell migration and wound closure, acting via cGMP, PKG, Src, and extracellular signal regulated kinase (ERK).

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“…NO activates the guanylyl cyclase and increases the synthesis of cyclic guanosine monophosphate [52]. The major target of NO is NO-sensitive guanylyl cyclase or soluble guanylyl cyclase.…”

Section: No-cyclic Guanosine Monophosphate (Cgmp) Pathwaymentioning

confidence: 99%

“…The major target of NO is NO-sensitive guanylyl cyclase or soluble guanylyl cyclase. Activation of the guanylyl cyclase results in conversion of guanosine triphosphate to the second messenger cGMP [52]. The NO/cGMP signaling cascade (Fig.5) is of importance in the cardiovascular and nervous systems, where it controls smooth muscle relaxation and modulation of synaptic transmission [53].…”

Section: No-cyclic Guanosine Monophosphate (Cgmp) Pathwaymentioning

confidence: 99%

“…Activation of guanylyl cyclase results in conversion of guanosine triphosphate to the second messenger cGMP [52] that in turn activates two specific cGMP-dependent protein-kinases (PKG I and II) important for vasodilatation and inhibition of platelet aggregation (PKG I) [54] . The second messenger (cGMP ) also inhibits the activity of phosphodiesterases (PDE II and III).…”

Section: No-cyclic Guanosine Monophosphate (Cgmp) Pathwaymentioning

confidence: 99%

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Cerebral protection in experimental cardiopulmonary resuscitation (with special reference to the effects of methylene blue)

Miclescu¹

2010

Acta Anaesthesiol Scand

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Although survival rates are increasing, brain injury continues to be a leading cause of death after cardiac arrest (CA). Permanent brain damage after CA is determined by limited tolerance to ischemia from CA and cardiopulmonary resuscitation (CPR), as well as the unique cerebral response to reperfusion after return of spontaneous circulation (ROSC). A major pathway leading to neurotoxic cascade and neuronal injury after CA involves the increased presence of reactive oxygen and nitrogen species generated during ischemia and reperfusion. The magnitude of cerebral oxidative injury induced by free radicals increased with the duration of CA (Paper I). Nitric oxide (NO), a free radical responsible for the formation of reactive nitrogen species, is increased during global ischemia from CA and reperfusion (Paper IV). Hypothetically, the administration of a drug that counteracts the overproduction of NO and also acts as a scavenger of oxygen free radicals might be warranted in order to reduce the damage caused by nitrosative and oxidative stress. For these purposes we used methylene blue (MB), an old dye that has been used in medicine for almost half a century, and an experimental pig model of 20 min of ventricular fibrillation (VF) to reflect a clinical scenario of ischemia/reperfusion injury. Administration of MB added to a hypertonic-hyperoncotic solution (MBHSD) that was started during CPR and continued for 50 min after ROSC increased short-term survival by decreasing myocardial damage, as well as cerebral peroxidation and inflammatory injury (Paper II). Immunostaining of cerebral tissue collected at different time points after CA and ROSC (Paper IV) provided experimental evidence that cortical blood-brain barrier (BBB) disruption begins as early as during the initial phase of untreated as well as treated CA. The results indicated that MB administration reduced the neurologic injury and BBB disruption considerably, but did not reverse the ongoing detrimental processes. The demonstrated positive effects of MB were related to a decrease of nitrite/nitrate tissue content, and thus to a decrease of excess NO due to the MB inhibitory effects on NOS isoforms. A mixture of MB in hypertonic sodium lactate (MBL) was investigated to facilitate administration of MB in "the field." Based on findings that MBL cardio-and neuroprotective properties were similar to those of MBHSD, there is reason to believe that the use of MBL might be extended during ongoing CPR and after ROSC (Paper III). It would therefore make sense to try using MB as a pharmacological neuroprotectant during or after clinical CPR in order to expand the temporal therapeutic window before other measures for neuroprotection such as hypothermia are available. Keywords: Cardiac arrest, cardiopulmonary resuscitation, reperfusion injury, methylene blue, nitric oxide, nitric oxide synthases, blood-brain barrier

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Regulation of Nitric Oxide-Sensitive Guanylyl Cyclase

Cited by 460 publications

References 144 publications

Regulation of multimers via truncated isoforms: a novel mechanism to control nitric-oxide signaling

Regulation of multimers via truncated isoforms: a novel mechanism to control nitric-oxide signaling

Nitrosyl-cobinamide (NO-Cbi), a new nitric oxide donor, improves wound healing through cGMP/cGMP-dependent protein kinase

Cerebral protection in experimental cardiopulmonary resuscitation (with special reference to the effects of methylene blue)

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