Nitric Oxide Toxicity in Neuronal Injury and Degeneration

Varner, Pamela D.; Beckman, Joseph S.

doi:10.1016/b978-012721985-1/50012-5

Cited by 12 publications

(7 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the increase in Vmax, YC-1 shifted the EC50 for NO by one order of magnitude to the left, thereby sensitizing the enzyme. As depicted in Figure 2B, this potentiating YC-1 effect was prominent at physiological NO concentrations ranging between 1 and 100 nM (Varner and Beckman, 1995), thus pointing towards a possible therapeutic use.…”

Section: Discussionmentioning

confidence: 74%

“…As shown in Figure 2A, YC-1 had a dramatic effect on NO activation. At a concentration of 200 ,uM, YC-1 increased the maximal sGC activity observed in the presence of NO by >40% (see also (Varner and Beckman, 1995). Figure 2B In order to investigate the underlying mechanism of the potentiating effect of YC-1, we used sGC activators other than NO.…”

Section: Results Sgc Stimulation By Yc-1mentioning

confidence: 99%

See 1 more Smart Citation

Sensitizing soluble guanylyl cyclase to become a highly CO-sensitive enzyme.

1996

View full text Add to dashboard Cite

It took at least a decade to realize that the toxic gas NO is the physiological activator of soluble guanylyl cyclase (sGC), thereby acting as a signaling molecule in the nervous and cardiovascular systems. Despite its rather poor sGC‐activating property, CO has also been implicated as a physiological stimulator of sGC in neurotransmission and vasorelaxation. Here, we establish YC‐1 as a novel NO‐independent sGC activator that potentiates both CO‐ and NO‐induced sGC stimulation. As this potentiating effect is also observed with protoporphyrin IX which activates sGC independently of a gaseous ligand, we conclude that stabilization of the enzyme's active configuration is the underlying mechanism of YC‐1′s action. Moreover, the results obtained with YC‐1 reveal that CO is capable of stimulating sGC to a degree similar to NO, and thus provide the molecular basis for CO functioning as a signaling molecule.

show abstract

Section: Discussionmentioning

confidence: 74%

Section: Results Sgc Stimulation By Yc-1mentioning

confidence: 99%

Sensitizing soluble guanylyl cyclase to become a highly CO-sensitive enzyme.

1996

View full text Add to dashboard Cite

show abstract

“…It has been reported that NOS inhibitors have an effect on blood pressure; therefore, it is difficult to quantify how and to what extend these effects might have specifically affected cognition (Varner and Beckman, 1994). However, it has been reported that when 3-Br 7-NI is injected systemically, it does not have hypertensive effects at a dose of 20 mg/kg (Rees et al, 1990).…”

Section: Discussionmentioning

confidence: 98%

Evidence for the involvement of neuronal nitric oxide synthase and soluble guanylate cyclase on cognitive functions in rats

et al. 2011

View full text Add to dashboard Cite

“…In particular neuropathologies, microglia and astrocytes are activated and contribute to oligodendrocyte and neuron damage and recovery (2-4). One novel but increasingly common currency for intercellular signaling in the CNS is nitric oxide (-NO) (5), a relatively benign and not very reactive gas with a biological half-life of seconds to minutes (6). However, -NO becomes highly reactive through secondary reactions (for example, with O2--) that produce more toxic species (ONOO-and -OH).…”

mentioning

confidence: 99%

■ REVIEW : Glial NO: Normal and Pathological Roles

Murphy¹,

Grzybicki

1996

Neuroscientist

View full text Add to dashboard Cite

All nervous system cell types can be induced with cytokines or bacterial products to make nitric oxide, at least in culture. The signaling pathways invoked by inducers that result in transcriptional activation of the nitric oxide synthase gene are becoming clear, and modulators of this induction have been discovered. Much suggestive and, recently, more definitive evidence has accumulated for induction of nitric oxide synthase in glial cells in vivo associated with viral infection, as well as in animal models of trauma, ischemia, and autoimmunity. Whether nitric oxide from this source contributes to or limits the attendant conditions is not yet clear. The Neuroscientist 2: [90][91][92][93][94][95][96][97][98][99] 1996 It is overly simplistic but convenient to divide the parenchymal, non-neuronal CNS cells into astrocytes, oligodendrocytes, and microglia. Each glial cell type contributes more or less extensively to the development of the CNS and to its steady state functions (for the &dquo;compleat&dquo; account, see reference 1 ). In particular neuropathologies, microglia and astrocytes are activated and contribute to oligodendrocyte and neuron damage and recovery (2-4). One novel but increasingly common currency for intercellular signaling in the CNS is nitric oxide (-NO) (5), a relatively benign and not very reactive gas with a biological half-life of seconds to minutes (6). However, -NO becomes highly reactive through secondary reactions (for example, with O2--) that produce more toxic species (ONOO-and -OH).Three isoforms of NO synthase (NOS) sharing considerable sequence homology catalyze the formation of NO in the nervous system (7). These are designated Types I (NOS 1 ), II (NOS2), and III (NOS3) (the order in which the cDNAs were cloned, not historically according to when their existence was first mooted). NOS3 (&dquo;endothelial&dquo; NOS) is a constitutive and largely membrane-bound enzyme dependent on calcium and calmodulin for activity. NOS is activated by intracellular calcium transients and found constitutively in particular neurons. The suggestion of a constitutive NOS in glial cells arose from observations of the production of a nitrosyl factor from stimulated astrocytes (8). With a variety of antibodies raised against NOS I and also NADPH diaphorase (NADPH-d) histochemistry (an indication of NOS activity under stringent conditions), the presence of NOS I in astrocytes has been verified (9-12).Questions about the nature of this constitutive astrocyte NOS and its role in vivo remain to be answered. In particular, and related to the growing interest in NOS 1 expression during the development of the nervous system (13), such roles for glial-derived NO may include programmed cell death, as well as neuronal guidance and differentiation.NOS2, a dimeric, heme-containing, soluble protein, is independent of calcium for activity (14). First described in activated macrophages, it has now been reported in a wide variety of normal and neoplastic cell types. In the CNS, all parenchymal and cerebrovascular cel...

show abstract

Nitric Oxide Toxicity in Neuronal Injury and Degeneration

Cited by 12 publications

References 67 publications

Sensitizing soluble guanylyl cyclase to become a highly CO-sensitive enzyme.

Sensitizing soluble guanylyl cyclase to become a highly CO-sensitive enzyme.

Evidence for the involvement of neuronal nitric oxide synthase and soluble guanylate cyclase on cognitive functions in rats

■ REVIEW : Glial NO: Normal and Pathological Roles

Contact Info

Product

Resources

About