Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

gamma-Immune protein-10 (gamma-IP10) is a cytokine whose expression has been shown to be induced by interferon-gamma. It is a member of a group of closely related cytokines (e.g., interleukin 8 and platelet factor 4) with chemotactic properties. gamma-IP10 has been detected in keratinocytes, lymphocytes, monocytes, and endothelial cells in immunologically mediated processes, such as positive tuberculin skin tests, and in growth-activated keratinocytes, such as in psoriasis. Keratinocytes in normal epidermis do not produce gamma-IP10. We tested the hypothesis that keratinocytes adjacent to dysplastic nevi and melanomas would produce gamma-IP10, perhaps as part of an immune response to a tumor, and that this response would not be seen in ordinary melanocytic nevi. We used an affinity-purified, polyclonal rabbit anti-gamma-IP10 antibody to examine 10 nevi with moderate to severe histologic dysplasia, one superficial spreading melanoma, and 10 compound melanocytic nevi with no features of dysplasia. As predicted, keratinocytes surrounding all of the cytologically atypical melanocytic lesions displayed strong staining with gamma-IP10. There was no staining of keratinocytes adjacent to ordinary melanocytic nevi. The observed keratinocyte staining with gamma-IP10 may be related to a host immune response to antigenically abnormal cells.
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PMID:Detection of cytokine-induced protein gamma-immune protein-10 (gamma-IP10) in atypical melanocytic proliferations. 172 47

Chemical modification of proteins is a common theme in their regulation. Nitrosylation of protein sulfhydryl groups has been shown to confer nitric oxide (NO)-like biological activities and to regulate protein functions. Several other nucleophilic side chains -- including those with hydroxyls, amines, and aromatic carbons -- are also potentially susceptible to nitrosative attack. Therefore, we examined the reactivity and functional consequences of nitros(yl)ation at a variety of nucleophilic centers in biological molecules. Chemical analysis and spectroscopic studies show that nitrosation reactions are sustained at sulfur, oxygen, nitrogen, and aromatic carbon centers, with thiols being the most reactive functionality. The exemplary protein, BSA, in the presence of a 1-, 20-, 100-, or 200-fold excess of nitrosating equivalents removes 0.6 +/- 0.2, 3.2 +/- 0.4, 18 +/- 4, and 38 +/- 10, respectively, moles of NO equivalents per mole of BSA from the reaction medium; spectroscopic evidence shows the proportionate formation of a polynitrosylated protein. Analogous reaction of tissue-type plasminogen activator yields comparable NO protein stoichiometries. Disruption of protein tertiary structure by reduction results in the preferential nitrosylation of up to 20 thus-exposed thiol groups. The polynitrosylated proteins exhibit antiplatelet and vasodilator activity that increases with the degree of nitrosation, but S-nitroso derivatives show the greatest NO-related bioactivity. Studies on enzymatic activity of tissue-type plasminogen activator show that polynitrosylation may lead to attenuated function. Moreover, the reactivity of tyrosine residues in proteins raises the possibility that NO could disrupt processes regulated by phosphorylation. Polynitrosylated proteins were found in reaction mixtures containing interferon-gamma/lipopolysaccharide-stimulated macrophages and in tracheal secretions of subjects treated with NO gas, thus suggesting their physiological relevance. In conclusion, multiple sites on proteins are susceptible to attack by nitrogen oxides. Thiol groups are preferentially modified, supporting the notion that S-nitrosylation can serve to regulate protein function. Nitrosation reactions sustained at additional nucleophilic centers may have (patho)physiological significance and suggest a facile route by which abundant NO bioactivity can be delivered to a biological system, with specificity dictated by protein substrate.
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PMID:Polynitrosylated proteins: characterization, bioactivity, and functional consequences. 864 72

Single cell analysis with capillary electrophoresis, a technique capable of detecting zeptomole quantities (10(-21) mole) of neurochemical species, has been used to demonstrate that lymphocytes are capable of active synthesis of dopamine and norepinephrine. Exposure of lymphocytes to catecholamines at concentrations as low as 10 nM leads to decreased proliferation and differentiation, e.g. interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and immunoglobulin (Ig). In addition, both inhibition of dopamine uptake with nomifensine and inhibition of packing of catecholamines into vesicles with tetrabenazine, results in significantly lower levels of dopamine and norepinephrine (p < 0.01 and p < 0.05, respectively). The catecholamine-dependent inhibition of T- and B-lymphocyte activity is mediated via an induction of a Bcl-2/Bax and Fas/FasL involved apoptosis. These findings indicate a novel mechanism for regulation of lymphocyte activity in the central nervous system, whereby elevated regional levels of catecholamines might lead to the immunoprivilege of the brain.
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PMID:Measurements of catecholamine-mediated apoptosis of immunocompetent cells by capillary electrophoresis. 937 67