Analysis of the Neuroprotective Effects of Various Nitric Oxide Donor Compounds in Murine Mixed Cortical Cell Culture

Vidwans, Aniruddha S.; Kim, Sungmee; Coffin, Deborah; Wink, David A.; Hewett, Sandra J.

doi:10.1046/j.1471-4159.1999.0721843.x

Cited by 61 publications

(25 citation statements)

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“…Indeed, whether NO is beneficial or detrimental is critically dependent on the concentration and duration of exposure as well as the cellular oxygen environment. [62][63][64][65][66][67]. Additionally, in the subset of astrocytes in which COX-2 and NOS-2 are co-expressed, a possible interplay may be functionally relevant as the enzymes have been shown to physically associate with one another in both in vitro and in vivo assays [68].…”

Section: Discussionmentioning

confidence: 99%

TGF-β1 reduces the heterogeneity of astrocytic cyclooxygenase-2 and nitric oxide synthase-2 gene expression in a stimulus-independent manner

Hamby

Hewett

2008

Prostaglandins & Other Lipid Mediators

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Transforming growth factor-β1 (TGF-β1) is upregulated by inflammatory mediators in several neurological diseases/disorders where it either participates in the pathology or provides protection. Often, the biological outcome of TGF-β1 is dependent upon changes in gene expression. Recently, we demonstrated that TGF-β1 enhances astrocytic nitric oxide production induced by lipopolysaccharide (LPS) plus interferon-γ (IFNγ) by increasing the number of astrocytes in a population that express NOS-2. The purpose of this study was two-fold: 1) to determine whether this effect occurs more generally by assessing the effect of TGF-β1 on another pro-inflammatory gene, cyclooxygenase-2 (COX-2); and 2) to assess stimulus specificity. We found that TGF-β1 augmented LPS plus IFNγ-induced COX-2 mRNA and protein expression, by nearly tripling the number of astrocytes that express COX-2. The effect was not stimulus-specific as TGF-β1 enhanced the number of astrocytes that expressed both COX-2 and NOS-2 protein when either IL-1β or TNFα was used in lieu of LPS. Collectively, these results suggest that TGF-β1 augments overall protein expression levels of select pro-inflammatory genes in astrocytes in a promiscuous manner by reducing the magnitude of noise in the cellular population.

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Section: Discussionmentioning

confidence: 99%

TGF-β1 reduces the heterogeneity of astrocytic cyclooxygenase-2 and nitric oxide synthase-2 gene expression in a stimulus-independent manner

Hamby

Hewett

2008

Prostaglandins & Other Lipid Mediators

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“…Nitrosative stress has a protective side where nitrosation of caspase 3 and 8 as well as PARP leads to protection against apoptosis 31-33 . Nitrosation and other oxidants closed NMDA channels preventing calcium influx [34][35][36][36][37][38] . Oxidative mechanisms such as nitration also have been shown to have biological signals of protection against apoptosis 39 .…”

Section: )mentioning

confidence: 99%

The chemical biology of nitric oxide: Implications in cellular signaling

Thomas¹,

Ridnour²,

Isenberg³

et al. 2008

Free Radical Biology and Medicine

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Nitric oxide (NO) has earned the reputation of being a signaling mediator with many diverse and often opposing biological activities. The diversity in response to this simple diatomic molecule comes from the enormous variety of chemical reactions and biological properties associated with it. In the last few years, the importance of steady state NO concentrations have emerged as a key determinant of its biological function. Precise cellular responses are differentially regulated by specific NO concentration. We propose 5 basic distinct concentration levels of NO activity; cGMP mediated processes ([NO] <1-30 nM; Akt phosphorylation ([NO] = 30-100 nM); stabilization of HIF-1α ([NO] = 100-300 nM); phosphorylation of p53 ([NO] > 400 nM) and nitrosative stress (1 µM). In general, lower NO concentrations promote cell survival and proliferation, while higher levels favor cell cycle arrest, apoptosis, and senescence. Free radical interactions will also influence NO signaling. One of the consequences of reactive oxygen species (ROS) generation is to reduce NO concentrations. This antagonizes the signaling of nitric oxide and in some cases results in converting a cell cycle arrest profile to a cell survival one. The resulting reactive nitrogen species (RNS) that are generated from these reactions can also have biological effects and increase oxidative and nitrosative stress responses. A number of factors determine the formation of NO and its concentration, such as diffusion, consumption, and substrate availability which are referred to as Kinetic Determinants for Molecular Target Interactions. These are the chemical and biochemical parameters that shape cellular responses to NO. Herein we discuss signal transduction and the chemical biology of NO in terms of the direct and indirect reactions.

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“…18 Yet a variety of exogenous NO donors have been shown to produce neuroprotective effects via nitrosation (NO+) chemistry. 19,20 In fact, recent in vitro and in vivo studies show that exogenous nitric oxide can act as a free radical scavenger and protect neurons (including dopaminergic neurons) from oxidative injury. 21,22 Although the molecular mechanisms of how exogenous NO donors contribute to neuroprotection are not completely understood, studies have shown that NO may confer neuroprotection by a variety of mechanisms.…”

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confidence: 99%

Preparation and Properties of Polyamines: Part II–Controlled and Sustained Release of Nitric Oxide (NO) from Nitrosated Polymers

Wang¹,

Teng

et al. 2009

Polym. J.

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The secondary amine moieties of polyamines prepared by the reactions of aliphatic diamines, and 1,5-difluoro-2,4-dinitrobenzene, were nitrosated using sodium nitrite and aqueous concentrated sulfuric acid at low temperature. Released NO from these polymers, suspended in water or phosphate buffer solutions (PBS), was measured at increasing time intervals by colorimetric techniques using Griess Reagent. Similar tests were also conducted with model compounds. In general, both the model compounds and the corresponding polymers exhibited similar NO release profiles, with apparent half lives up to 88 h and 81 h, respectively. They were strongly dependent on the length of the alkyl chains derived from the primary amines used for the preparation of these NO-releasing materials. Results from in vitro studies using low molecular weight NO-releasing compounds with PC-12 cell are also reported. High concentration of NO induced neuronal cell death. On the other hand, low concentration of NO inhibited cell death induced by oxidative stress. This suggests that cell survival effect is NO-dependent.KEY WORDS: Nitrosated Polyamines / Nitric Oxide / Controlled Release / Cell Culture / Nitrogen monoxide, NO, more commonly known as nitric oxide, plays a critical role in a variety of biological functions.1-3 Towards the end of 1987, the discovery that mammalian cells synthesize nitric oxide, which regulates virtually every critical cellular function, has led to an explosion of research activities.4,5 For example, NO, which is produced from the amino acid L-Arginine in vivo, is involved in the regulation of neurotransmissions, blood pressure, and immune response.6 Nitric oxide can exist as a radical, NO , as a positively charged ion, NO þ (nitrosonium ion), and as nitroxyl anion (NO À ). 7 This allows NO to participate in numerous important biological functions mentioned above as well as others. Diseased states ensue when the bioavailability of NO, for a variety of reasons, becomes impaired. 8,9 Exogenous NO, derived from various families of NO-donors, has been used to ameliorate debilitating symptoms of a few of these diseases. 10A vast majority of NO-donors are low molecular weight compounds including: nitrates, nitrites, N-nitroso, C-nitroso, certain heterocycles, metal-NO complexes, and diazeniumdiolates. 10 Depending on the chemical nature of these compounds, NO is released spontaneously either in the presence or the absence of a catalyst. In the case of diazeniumdiolates, half-life of NO generation can be varied between 2 s to 56 h by changing the nature of the backbone to which the diazenuimdiolate moiety is attached. 11In contrast to the low molecular weight NO-donors, which have been investigated extensively, polymeric NO donors are new arrivals in this field. Since NO is known to prevent platelet aggregation, 12 NO generating polymers can be used as biomaterials, which are likely to come in contact with blood. In addition, the biocompatibility of implanted chemical sensors can be enhanced significantly by using NO-releasing...

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Analysis of the Neuroprotective Effects of Various Nitric Oxide Donor Compounds in Murine Mixed Cortical Cell Culture

Cited by 61 publications

References 61 publications

TGF-β1 reduces the heterogeneity of astrocytic cyclooxygenase-2 and nitric oxide synthase-2 gene expression in a stimulus-independent manner

TGF-β1 reduces the heterogeneity of astrocytic cyclooxygenase-2 and nitric oxide synthase-2 gene expression in a stimulus-independent manner

The chemical biology of nitric oxide: Implications in cellular signaling

Preparation and Properties of Polyamines: Part II–Controlled and Sustained Release of Nitric Oxide (NO) from Nitrosated Polymers

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