1,721,157 research outputs found
Nitric oxide: an inhibitor of NF-κB/Rel system in glial cells
No full textNitric oxide (NO) has been reported to regulate
NF-kB, one of the best-characterized transcription factors playing
important roles in many cellular responses to a large variety
of stimuli. NO has been suggested to induce or inhibit the
activation of NF-kB, its effect depending, among others, on the
cell type considered. In this review, the inhibitory effect of NO
on NF-kB (and subsequent suppression of NF-kB-dependent
gene expression) in glial cells is reported. In particular, exogenous
and endogenous NO has been observed to keep NF-kB
suppressed, thus preventing the expression of NF-kB-induced
genes, such as inducible NO synthase itself or HIV-1 long terminal
repeat. Furthermore, the possible molecular mechanisms
of NO-mediated NF-kB inhibition are discussed. More specifically,
NO has been reported to suppress NF-kB activation inducing
and stabilizing the NF-kB inhibitor, IkB-a. On the other
hand, NO may inhibit NF-kB DNA binding through S-nitrosylation
of cysteine residue (i.e., Cys62) of the p50 subunit. As a
whole, a novel concept that the balance of intracellular NO
levels may control the induction of NF-kB in glial cells has been
hypothesized
Nitric oxide pathway in lower metazoans
No full textThe presence of nitric oxide (NO) pathway has been well demonstrated in the main invertebrate groups,
showing parallel findings on the role of NO in vertebrates and invertebrates. Noteworthy is the example
of the role played by the nitrergic pathway in the sensorial functions, mainly in olfactory-like systems. On
the other hand, the emerging molecular information about NOSs from lower metazoans (Porifera, cnidarians
up to higher invertebrates) suggests that NO pathways might represent examples of a parallel evolution
of the NOS prototypes in different animal lineages. Nevertheless, increasing evidence suggests that
NO is one of the earliest and most widespread signaling molecules in living organisms.
Here, we attempt to provide a survey of current knowledge of the synthesis and possible roles of NO
and the related signaling pathway in lower metazoans (i.e., Porifera and Cnidaria), two phyla forming
a crucial bridge spanning the evolutionary gap between the protozoans and higher metazoans. From
the literature data here reported, it emerges that future research on the biological roles of NO in basal
metazoans is likely to be very important for understanding the evolution of signaling systems
Amyloid-β 25-35 induces neurotoxicity through the up-regulation of astrocytic system xc −
Full text linkAmyloid-β (Aβ) deposition, a hallmark of Alzheimer’s disease, is known to induce free radical production and oxidative stress, leading to neuronal damage. During oxidative stress, several cell types (including astrocytes) can activate the nuclear factor erythroid 2-related factor 2 (Nrf2), a regulator of several phase II detoxifying and antioxidant genes, such as the System Xc− subunit xCT. Here, we studied (i) the effect of the Aβ fragment 25-35 (Aβ25-35 ) on Nrf2-dependent System Xc − expression in U373 human astroglial cells and (ii) the effect of Aβ25-35-induced astrocytic response on neuronal cell viability using an in vitro co-culture system. We found that Aβ25-35 was able to activate an antioxidant response in astrocytes, by inducing both Nrf2 activation and System Xc− up-regulation. However, this astrocytic response caused an enhanced cell mortality of co-cultured SH-SY5Y cells, taken as a neuronal model. Consistently, the specific System Xc− inhibitor sulfasalazine prevented the increase of both neuronal mortality and extracellular glutamate levels, thus indicating that the neurotoxic effect was due to an augmented release of glutamate through the transporter. The involvement of NMDA receptor activation in this pathway was also demonstrated using the specific inhibitor MK801 that completely restored neuronal viability at the control levels. The present study sheds light on the Nrf2/system Xc− pathway in the toxicity induced by Aβ25-35 and may help to better understand the involvement of astrocytes in neuronal death during Alzheimer’s disease
Molecular bases for the anti-HIV-1 effect of NO. Commentary
No full textIn infected human cells, nitric oxide (NO) has been shown to inhibit the replication of the human immunodeficiency virus-1 (HIV-1), the etiological agent of AIDS. Evidence suggests that NO may regulate HIV-1 replication by affecting the sulphydryl redox state. In this respect, it has been very recently demonstrated that NO-donors inactivate the HIV-1-encoded protease and reverse transcriptase in vitro. Further viral and host NO targets may be envisaged. Although no data are available on the anti-HIV-1 effect of NO in vivo, NO-releasing drugs, clinically used in the treatment of cardiovascular disorders, may represent a novel class of molecules for decreasing virus replication. Here, the possible molecular bases for the anti-HIV-1 effect of NO are discussed
Nitric oxide inhibits falcipain, the Plasmodium falciparum trophozoite cysteine protease
No full textNitric oxide (NO) is a pluripotent regulatory molecule possessing, among others, an antiparasitic activity. In the present study, the inhibitory effect of NO on the catalytic activity of falcipain, the papain-like cysteine protease involved in Plasmodium falciparum trophozoite hemoglobin degradation, is reported. In particular, NO donors S-nitrosoglutathione (GSNO), (±)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-n-3-hexenamide (NOR-3), 3-morpholinosydnonimine (SIN-1), and sodium nitroprusside (SNP) inhibit dose-dependently the falcipain activity present in the P. falciparum trophozoite extract, this effect likely attributable to S-nitrosylation of the Cys25 catalytic residue. The results represent a new insight into the modulation mechanism of falcipain activity, thereby being relevant in developing new strategies for inhibition of the P. falciparum life cycle. (C) 2000 Academic Press
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Inhibition of nitric-oxide synthase-I (NOS-I)-dependent nitric oxide production by lipopolysaccharide plus interferon-gamma is mediated by arachidonic acid. Effects on NFkappaB activation and late inducible NOS expression.
No full textPrevious results have indicated that lipopolysaccharide (LPS) plus interferon-gamma (IFNgamma) inhibits nitric-oxide synthase (NOS)-I activity in glial cells. We report here that arachidonic acid ( AA) plays a pivotal role in this response, which was consistently reproduced in different glial cell lines and in primary rat astrocytes. This notion was established using pharmacological inhibitors of phospholipase A(2) (PLA(2)), cytosolic PLA(2) (cPLA(2)) antisense oligonucleotides, and AA add-back experiments. This approach not only allowed the demonstration that AA promotes inhibition of NOS-I activity but also produced novel experimental evidence that LPS/IFNgamma itself is a potential stimulus for NOS-I. Indeed, LPS/IFNgamma fails to generate nitric oxide (NO) via NOS-I activation simply because it activates the AA-dependent signal that impedes NOS-I activity. Otherwise, LPS/IFNgamma promotes NO formation, sensitive to exogenous AA, in cells in which cPLA(2) is pharmacologically inhibited or genetically depleted. Because NO suppresses the NFkappaB-dependent NOS-II expression, inactivation of NOS-I by the LPS/IFNgamma-induced AA pathway provides optimal conditions for NFkappaB activation and subsequent NOS-II expression. Inhibition of cPLA(2) activity, while reducing the availability of AA, consistently inhibited NFkappaB activation and NOS-II mRNA induction and delayed NO formation. These responses were promptly re-established by addition of exogenous AA. Finally, we have demonstrated that the LPS/IFNgamma-dependent tyrosine phosphorylation of NOS-I and inhibition of its activity are mediated by endogenous AA
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