Prolonged exposures of cerebellar granule neurons to S-nitroso-N-acetylpenicillamine (SNAP) induce neuronal damage independently of peroxynitrite

Fatokun, Amos A.; Stone, T.W.; Smith, Robert A.

doi:10.1016/j.brainres.2008.06.109

Cited by 15 publications

(10 citation statements)

References 59 publications

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“…Therefore, the identification of other microglia-released factors involved in neuroprotection will likely contribute to explaining why other types of neurotoxicity (a shift of CGNs to nondepolarizing con-ditions or excitotoxicity) are significantly reverted by MCM, but not by exogenous SOD1. Differences in SOD1 neuroprotection against different toxic stimuli are in line with previous works that have or have not found neuroprotective effects of SOD1 in nonconditioned media, sometimes using very high amounts of exogenously added protein [60,61,62,63,64,65,66]. To further complicate this situation, it has to be considered that SOD1 may act on target cells both through its catalytic activity and through receptor interaction [46,47].…”

Section: Discussionmentioning

confidence: 70%

“…While superoxide dismutase is usually released by cells in its SOD3 isoform [58,59], also SOD1 is released by several cell lines [31,32,33,34]. Moreover, high concentrations of SOD1 may protect neurons from some toxic insults [60,61,62,63,64,65,66]. Here we show that SOD1 is produced and released by microglia and is a neuroprotective factor against 6-OHDA neurotoxicity in CGNs.…”

Section: Discussionmentioning

confidence: 84%

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Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA Neurotoxicity

Polazzi¹,

Mengoni²,

Caprini

et al. 2012

Neurosignals

7,257

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Microglial-neuronal interactions are essential for brain physiopathology. In this framework, recent data have changed the concept of microglia from essentially macrophagic cells to crucial elements in maintaining neuronal homeostasis and function through the release of neuroprotective molecules. Using proteomic analysis, here we identify copper-zinc superoxide dismutase (SOD1) as a protein produced and released by cultured rat primary microglia. Evidence for a neuroprotective role of microglia-derived SOD1 resulted from experiments in which primary cerebellar granule neurons (CGNs) were exposed to the dopaminergic toxin 6-hydroxydopamine (6-OHDA). Microglial conditioned medium, in which SOD1 had accumulated, protected CGNs from degeneration, and neuroprotection was abrogated by SOD1 inhibitors. These effects were replicated when exogenous SOD1 was added to a nonconditioned medium. SOD1 neuroprotective action was mediated by increased cell calcium from an external source. Further experiments demonstrated the specificity of SOD1 neuroprotection against 6-OHDA compared to other types of neurotoxic challenges. SOD1, constitutively produced and released by microglia through a lysosomal secretory pathway, is identified here for the first time as an essential component of neuroprotection mediated by microglia. This novel information is relevant to stimulating further studies of microglia-mediated neuroprotection in in vivo models of neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 84%

Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA Neurotoxicity

Polazzi¹,

Mengoni²,

Caprini

et al. 2012

Neurosignals

7,257

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“…Use of a thin outer layer of a highly crosslinked polymer could also be employed to further retard the leaching of SNAP from the E2As polymer. Applications of SNAP have been reported to cause hypotension [68, 69], hyperglycemia and impaired insulin secretion [69], and decreased cell viability [70–72]. Endogenous thiols and superoxide dismutase will reduce many of these adverse effects.…”

Section: Resultsmentioning

confidence: 99%

Long-term nitric oxide release and elevated temperature stability with S-nitroso-N-acetylpenicillamine (SNAP)-doped Elast-eon E2As polymer

et al. 2013

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Nitric oxide (NO) is known to be a potent inhibitor of platelet activation and adhesion. Healthy endothelial cells that line the inner walls of all blood vessels exhibit a NO flux of 0.5~4×10−10 mol cm−2 min−1 that helps prevent thrombosis. Materials with a NO flux that is equivalent to this level are expected to exhibit similar anti-thrombotic properties. In this study, five biomedical grade polymers doped with S-nitroso-N-acetylpenicillamine (SNAP) were investigated for their potential to control the release of NO from the SNAP within the polymers, and further control the release of SNAP itself. SNAP in the Elast-eon E2As polymer creates an inexpensive, homogeneous coating that can locally deliver NO (via thermal and photochemical reactions) as well slowly release SNAP. Furthermore, SNAP is surprisingly stable in the E2As polymer, retaining 82% of the initial SNAP after 2 months storage at 37°C. The E2As polymer containing SNAP was coated on the walls of extracorporeal circuits (ECC) and exposed to 4 h blood flow in a rabbit model of extracorporeal circulation to examine the effects on platelet count, platelet function, clot area, and fibrinogen adsorption. After 4 h, platelet count was preserved at 100±7% of baseline for the SNAP/E2As coated loops, compared to 60±6% for E2As control circuits (n=4). The SNAP/E2As coating also reduced the thrombus area when compared to the control (2.3±0.6 and 3.4±1.1 pixels/cm2, respectively). The results suggest that the new SNAP/E2As coating has potential to improve the thromboresistance of intravascular catheters, grafts, and other blood contacting medical devices, and exhibits excellent storage stability compared to previously reported NO release polymeric materials.

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“…The co-administration of intravenous fluids counteracted the blood pressure fall but this could pose significant difficulties in a clinical situation. SNAP administration has been shown to cause hypotension [35], hyperglycemia [36] and decreased cell viability [37–39]. However, most of these adverse effects are ameliorated in the presence of endogenous thiols and superoxide dismutase.…”

Section: Discussionmentioning

confidence: 99%

The hemocompatibility of a nitric oxide generating polymer that catalyzes S-nitrosothiol decomposition in an extracorporeal circulation model

et al. 2011

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Nitric oxide (NO) generating (NOGen) materials have been shown previously to create localized increases in NO concentration by the catalytic decomposition of blood S-nitrosothiols (RSNO) via copper (Cu)-containing polymer coatings and may improve extracorporeal circulation (ECC) hemocompatibility. In this work, a NOGen polymeric coating composed of a Cuo-nanoparticle (80 nm)-containing hydrophilic polyurethane (SP-60D-60) combined with the intravenous infusion of an RSNO, S-nitroso-N-acetylpenicillamine (SNAP), is evaluated in a 4 h rabbit thrombogenicity model and the anti-thrombotic mechanism is investigated. Polymer films containing 10 wt.% Cuo-nanoparticles coated on the inner walls of ECC circuits are employed concomitantly with systemic SNAP administration (0.1182 μmol/kg/min) to yield significantly reduced ECC thrombus formation compared to polymer control + systemic SNAP or 10 wt.% Cu NOGen + systemic saline after 4 h blood exposure (0.4 ± 0.2 NOGen/SNAP vs 4.9 ± 0.5 control/SNAP or 3.2 ± 0.2 pixels/cm2 NOGen/saline). Platelet count (3.9 ± 0.7 NOGen/SNAP vs 1.8 ± 0.1 control/SNAP or 3.0 ± 0.2 × 108/ml NOGen/saline) and plasma fibrinogen levels were preserved after 4 h blood exposure with the NOGen/SNAP combination vs either the control/SNAP or the NOGen/saline groups. Platelet function as measured by aggregometry (51 ± 9 NOGen/SNAP vs 49 ± 3% NOGen/saline) significantly decreased in both the NOGen/SNAP and NOGen/saline groups while platelet P-selectin mean fluorescence intensity (MFI) as measured by flow cytometry was not decreased after 4 h on ECC to ex vivo collagen stimulation (26 ± 2 NOGen/SNAP vs 29 ± 1 MFI baseline). Western blotting showed that fibrinogen activation as assessed by Aγ dimer expression was reduced after 4 h on ECC with NOGen/SNAP (68 ± 7 vs 83 ± 3% control/SNAP). These results suggest that the NOGen polymer coating combined with SNAP infusion preserves platelets in blood exposure to ECCs by attenuating activated fibrinogen and preventing platelet aggregation. These NO-mediated platelet changes were shown to improve thromboresistance of the NOGen polymer-coated ECCs when adequate levels of RSNOs are present.

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Prolonged exposures of cerebellar granule neurons to S-nitroso-N-acetylpenicillamine (SNAP) induce neuronal damage independently of peroxynitrite

Cited by 15 publications

References 59 publications

Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA Neurotoxicity

Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA Neurotoxicity

Long-term nitric oxide release and elevated temperature stability with S-nitroso-N-acetylpenicillamine (SNAP)-doped Elast-eon E2As polymer

The hemocompatibility of a nitric oxide generating polymer that catalyzes S-nitrosothiol decomposition in an extracorporeal circulation model

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