J Biol Chem 2001,
PMID: 11316802
Fabrizi, C; Silei, V; Menegazzi, M; Salmona, M; Bugiani, O; Tagliavini, F; Suzuki, H; Lauro, G M
A synthetic peptide consisting of amino acid residues 106-126 of the human prion protein (PrP-(106--126)) has been previously demonstrated to be neurotoxic and to induce microglial activation. The present study investigated the expression of the inducible form of the nitric-oxide synthase (NOS-II) in human microglial cells treated with PrP-(106--126). Using reverse transcriptase-polymerase chain reaction, we found that PrP-(106--126) induces NOS-II gene expression after 24 h of treatment and that this effect is accompanied by a peak of nuclear factor kappa B (NF-kappa B) binding at 30 min as evaluated by electrophoretic mobility shift assay. Since our previous data demonstrated tumor necrosis factor-alpha (TNF-alpha) to be a potent inducer of NOS-II in these cells, we analyzed the expression of this cytokine in PrP-(106--126)-treated microglia. PrP-(106--126) caused the release of TNF-alpha as detected by enzyme-linked immunosorbent assay, and a blocking antibody, anti-TNF-alpha, abolished NOS-II induction elicited by this peptide. Moreover, PrP-(106-126) activates p38 mitogen-activated protein kinase, and the inhibition of this pathway determines the ablation of NF-kappa B binding induced by this fragment peptide.
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Text Mining Data
nitric-oxide synthase → mitogen activated protein kinase: "
The stimulation of inducible
nitric-oxide synthase by the prion protein fragment 106 -- 126 in human microglia is tumor necrosis factor-alpha dependent and
involves p38
mitogen activated protein kinase
"
NOS-II → PrP-: "
Using reverse transcriptase-polymerase chain reaction, we found that PrP- ( 106 -- 126 ) induces NOS-II gene expression after 24 h of treatment and that this effect is accompanied by a peak of nuclear factor kappa B (NF-kappa B) binding at 30 min as evaluated by electrophoretic mobility shift assay
"
TNF-alpha → PrP-: "
PrP- ( 106 -- 126 ) caused the release of TNF-alpha as detected by enzyme linked immunosorbent assay, and a blocking antibody, anti-TNF-alpha, abolished NOS-II induction elicited by this peptide
"
mitogen activated protein kinase → PrP-: "
Moreover, PrP- ( 106-126 ) activates p38 mitogen activated protein kinase , and the inhibition of this pathway determines the ablation of NF-kappa B binding induced by this fragment peptide
"
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