Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NO appears as an important determinant in auto and paracrine macrophage function. We hypothesized that NO switches monocyte/macrophage function from a pro- to an anti-inflammatory phenotype by activating anti-inflammatory properties of the peroxisome proliferator-activated receptor (PPAR)gamma. NO-releasing compounds (100 micro M S-nitrosoglutathione or 50 micro M spermine-NONOate) as well as inducible NO synthase induction provoked activation of PPARgamma. This was proven by EMSAs, with the notion that supershift analysis pointed to the involvement of PPARgamma. PCR analysis ruled out induction of PPARgamma mRNA as a result of NO supplementation. Reporter assays, with a construct containing a triple PPAR response element in front of a thymidine kinase minimal promoter driving the luciferase gene, were positive in response to NO delivery. DNA binding capacity as well as the transactivating capability of PPARgamma were attenuated by addition of the antioxidant N-acetyl-cysteine or in the presence of the NO scavenger 2-phenyl-4,4,5,6-tetramethyl-imidazoline-1-oxyl 3-oxide. Having established that NO but not lipophilic cyclic GMP analogs activated PPARgamma, we verified potential anti-inflammatory consequences. The oxidative burst of macrophages, evoked by phorbol ester, was attenuated in association with NO-elicited PPARgamma activation. A cause-effect relationship was demonstrated when PPAR response element decoy oligonucleotides, supplied in front of NO delivery, allowed to regain an oxidative response. PPARgamma-mediated down-regulation of p47 phagocyte oxidase, a component of the NAD(P)H oxidase system, was identified as one molecular mechanism causing inhibition of superoxide radical formation. We conclude that NO participates in controlling the pro- vs anti-inflammatory phenotype of macrophages by modulating PPARgamma.
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PMID:Activation of peroxisome proliferator-activated receptor gamma by nitric oxide in monocytes/macrophages down-regulates p47phox and attenuates the respiratory burst. 1219 33

Epstein-Barr virus (EBV)-specific immunoblot analysis was used to reveal the molecular diversity of immunoglobulin (Ig) G and IgA antibody responses against Epstein-Barr nuclear antigen (EBNA), early antigen (EA), and viral capsid antigen (VCA) in serum samples from patients with nasopharyngeal carcinoma (NPC) and control subjects, by use of immunofluorescence assay (IFA). Control donors (n=150) showed IgG responses to few EBV proteins--VCA-p18, VCA-p40, EBNA1, and Zebra--and sporadically weak IgA reactivity to EBNA1 and VCA-p18. Patients with NPC stage 1 (n=6) had similar response patterns. Patients with NPC stage 2-4 (n=132) showed significantly more diverse IgG and IgA responses to EA and VCA proteins--VCA-p18/-p40, EBNA1, Z-encoded broadly reactive activator, and EAd-p47/54, -DNAse, -thymidine kinase, and -p138. No correlation was found between IFA titers and the number of EBV proteins recognized by IgG or IgA. Our results reveal dissimilarity between EBV polypeptides recognized by IgG and IgA antibodies, which suggests independent B cell triggering events.
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PMID:Molecular diversity of Epstein-Barr virus IgG and IgA antibody responses in nasopharyngeal carcinoma: a comparison of Indonesian, Chinese, and European subjects. 1519 43