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

Maspin, a mammary serine protease inhibitor, was originally reported to be a tumor suppressor gene in breast and prostate cancers. The expression pattern of the maspin gene differs among cancer types and normal tissue however, and its significance as a tumor suppressor has been questioned. In this study, maspin expression and/or allele-specific methylation status were investigated in five melanoma cell lines and a normal human epidermal melanocyte (NHEM) cell line, and 80 surgically resected tumors (40 melanomas and 40 melanocytic nevi). One (HMV-I) of five melanoma cell lines overexpressed maspin protein whereas the remaining four melanoma cell lines and NHEM did not. The 19 CpG sites of the maspin promoter region were extensively hypomethylated in HMV-I, a maspin-positive cell line, and those of the remaining four melanoma and NHEM cell lines were hypermethylated. Furthermore, maspin-negative cell lines exhibited activation after treatment with 5-aza-2'-deoxycytidine, a DNA demethylating agent. Immunoreactivity for maspin was negative in normal skin melanocytes and 40 melanocytic nevi, but five (12.5%) of 40 melanomas were positive. The methylation status judged by the methylation-specific PCR method was inversely correlated with maspin protein expression in vitro and in vivo. These results suggest that maspin expression in normal skin melanocytes and melanocytic nevi may be repressed in a cell-type-specific manner, whereas maspin is expressed aberrantly in a subset of melanoma cells by epigenetic modification. Further investigations are required to determine the significance of aberrant maspin expression.
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PMID:Aberrant expression of the maspin gene associated with epigenetic modification in melanoma cells. 1508 68

Purified human alpha(1) proteinase inhibitor, a plasma glycoprotein with a molecular weight of 5.3 x 10(4) daltons and a major serine protease inhibitor has been covalently coupled to dextrans with molecular weights of 1.77 x 10(4) and 1.03 x 10(4) daltons. The coupled conjugates were soluble in aqueous medium and stable up to 6 months at +5 degrees C. Increased moles of dextran/mole protein ratio during coupling resulted in progressive decreases of inhibitory capacity, immunogenicity, and the association constant (k(assoc)) between the enzyme and the inhibitor. Compared to the native protein, the soluble conjugates showed improved stability at pH 3.0 and heat stability at 60 degrees C. At 60 degrees C, no loss of inhibitory capacity has been seen up to 60 min for the conjugates during which time the native protein lost greater than 90% of its inhibitory capacity. The presence of antioxidant catalase was needed to prevent oxidative degradation by hydrogen peroxide.
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PMID:Preparation and characterization of a soluble dextran alpha(1) proteinase inhibitor complex. 1855 39

Human alpha(1)-proteinase inhibitor (alpha(1)-PI), also known as alpha(1)-antitrypsin, is the most abundant plasma serine protease inhibitor (serpin). It is best recognized for inhibition of neutrophil elastase. The alpha(1)-PI interactions with non-protease ligands were investigated mainly in regards to those molecules that may block the aggregation of alpha(1)-PI Z mutant. The objective of this study was to evaluate the potential of alpha(1)-PI to bind small non-peptide ligands of pharmaceutical interest that may attain additional properties to currently available alpha(1)-PI therapeutic preparations. Among putative ligands of bio-medical interest examined in this study, all-trans retinoic acid (RA) was selected due to its recently proposed roles in the lungs, and as an efficient optical probe. The results of this study, including absorption spectroscopy data, fluorescence quenching and the protein-induced chirality of the visible circular dichroism strongly suggest that alpha(1)-PI does bind RA in vitro to non-covalent complexes of up to two moles of RA per one mole of the protein. To our knowledge, this is the first report that provides experimental evidence of the alpha(1)-PI potential towards bi-functional drugs via a combination with RA, or potentially other molecules of pharmaceutical interest, that ultimately, may enhance currently available alpha(1)-PI therapies.
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PMID:Interactions of alpha1-proteinase inhibitor with small ligands of therapeutic potential: binding with retinoic acid. 1949 39