Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A large number of hepatoma cell lines has been used to study expression and regulation of liver-specific function. However these cells, even the most differentiated, are morphologically far from hepatocytes. In no case is the typical hepatocyte cell polarity well maintained. Cell hybridization has been used as a potential means for turning on specific genes. From hybrids between well differentiated Fao rat hepatoma cells and WI 38 human fibroblasts, we have attempted to isolate segregated cells that are highly differentiated and polarized. Such cells, detected in aged cultures of only one hybrid (WIF12), were isolated by subcloning. One subclone, WIF12-1 was analyzed. Expression of liver-specific functions extinguished in the original hybrid is restored in all WIF12-1 cells at a very high level, similar to that of hepatocytes and 5-30 times higher that that of parental cells. Moreover human genes coding for liver-specific proteins (albumin, fibrinogen, and alcohol dehydrogenase) are actively expressed. WIF12-1 cells have acquired a polarized phenotype as attested by the presence of bile canaliculi between adjacent cells and by the asymmetrical localization of apical (Mg(2+)-ATPase, gamma-glutamyl transpeptidase) and basolateral membrane markers. The bile canaliculi formed are dynamic and functional structures, characterized by long periods of expansion followed by rapid contractions. The ability to polarize is a general and permanent property of WIF12-1 cells. These cells appear to constitute a valid model for the in vitro study of hepatocyte cell polarity, membrane domain formation and mechanisms of membrane protein sorting.
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PMID:Hybrid cell lines constitute a potential reservoir of polarized cells: isolation and study of highly differentiated hepatoma-derived hybrid cells able to form functional bile canaliculi in vitro. 195 80

In the present experiments, selective quenching by trinitrophenyl groups as well as steady-state fluorescence polarization and differential polarized phase fluorescence techniques, using three different lipid soluble fluorophores, were used to directly examine the fluidity of the exofacial and cytofacial leaflets of rat small intestinal brush-border membranes. These studies revealed that the fluidity of the exofacial hemileaflet was greater than the cytofacial hemileaflet. Differences in the distribution of phosphatidylcholine and phosphatidylethanolamine, as assessed by phospholipase A2 treatment and trinitrophenylation of aminophospholipids, were, at least partially, responsible for the asymmetrical fluidity of the hemileaflets. Moreover, in vitro addition of benzyl alcohol (final concn 25 mM) preferentially fluidized the exofacial leaflet and concomitantly decreased leucine aminopeptidase activity but did not affect the activities of maltase, sucrase, alkaline phosphatase, or gamma-glutamyltranspeptidase. In vivo addition of the membrane-mobility agent 2-(2-methoxyethoxy)ethyl 8-(cis-2-n-octylcyclopropyl)octanate] (A2C) (final concn 7.5 microM) preferentially fluidized the cytofacial leaflet and increased Na(+)-gradient-dependent D-glucose transport but not Na(+)-gradient-dependent L-leucine transport.
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PMID:Characterization and modulation of rat small intestinal brush-border membrane transbilayer fluidity. 201 33

Using an immunochemical method, we measured the activity of the mitochondrial isoenzyme (mAST) of aspartate amino-transferase (EC 2.6.1.1, AST) in the serum of 687 subjects attending the Centre for Preventive Medicine for a health examination. The distributions of the activities were asymmetrical, with mean values of 1.8 U/L (SD 2.0) for men and 1.4 U/L (SD 1.6) for women. The average ratio of mitochondrial to total AST activity was 0.051 (range 0-0.42). In this unselected population we found no change in the mitochondrial activity or in the mitochondrial-to-total ratio attributable to alcohol consumption, even in subjects who consumed more than 88 g per day. Of 35 men with an alcohol consumption greater than 88 g/d, 19 had a serum gamma-glutamyltransferase activity of greater than or equal to 60 U/L, 17 had glutamate dehydrogenase values greater than or equal to 5 U/L, and only nine had an mAST activity greater than or equal to 3 U/L (values corresponding to the 80th percentiles of the total population). We conclude that the test is not particularly useful as a screening procedure in an unselected population under present-day conditions of measurement.
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PMID:Serum mitochondrial aspartate aminotransferase activity: not useful as a marker of excessive alcohol consumption in an unselected population. 256 16

1,2,3,4-Diepoxybutane (DEB) is a prominent carcinogenic metabolite of 1,3-butadiene (1,3-BD), an important industrial chemical and an environmental pollutant found in cigarette smoke and automobile exhaust. DEB is capable of inducing a variety of genotoxic effects, including point mutations, large deletions, and chromosomal aberrations. The mutagenicity and carcinogenicity of DEB are thought to result from its ability to form bifunctional DNA-DNA adducts by sequentially alkylating two nucleobases within the DNA double helix. We recently reported that DEB-induced DNA-DNA cross-linking leads to the formation of 1,4-bis-(guan-7-yl)-2,3-butanediol (bis-N7G-BD) adducts [Park, S., and Tretyakova, N. (2004) Structural characterization of the major DNA-DNA cross-link of 1,2,3,4-diepoxybutane. Chem. Res. Toxicol. 17 (2), 129-136]. However, guanine-guanine cross-linking by DEB cannot explain the development of A:T base pair mutations following exposure to DEB and 1,3-BD. In the present work, four asymmetrical DNA-DNA cross-links involving both adenine and guanine nucleobases were identified in double-stranded DNA treated with racemic DEB. These novel lesions were assigned the structures of 1-(aden-1-yl)-4-(guan-7-yl)-2,3-butanediol (N1A-N7G-BD), 1-(aden-3-yl)-4-(guan-7-yl)-2,3-butanediol (N3A-N7G-BD), 1-(aden-7-yl)-4-(guan-7-yl)-2,3-butanediol (N7A-N7G-BD), and 1-(aden-N6-yl)-4-(guan-7-yl)-2,3-butanediol (N6A-N7G-BD), based on the comparison of their MS/MS spectra, HPLC retention times, and UV spectra with those of the corresponding authentic standards prepared independently. Although guanine-adenine lesions are approximately 10 times less abundant in DEB-treated double-stranded DNA than the corresponding bis-N7G cross-links, N1A-N7G-BD and N6A-N7G-BD are more hydrolytically stable and, if formed in vivo, may accumulate in target tissues. HPLC-ESI-MS/MS analysis of guanine-adenine DEB cross-links induced in synthetic DNA duplexes 5'-(GGT)5, 5'-(GT)7G, and 5'-(GAA)5 (+-strand) demonstrate that G-A cross-linking by DEB produces primarily 1,3-interstrand N1A-N7G lesions. The formation of bifunctional guanine-adenine adducts is likely to contribute to AT base pair substitutions and deletion mutations following DEB exposure.
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PMID:Guanine-adenine DNA cross-linking by 1,2,3,4-diepoxybutane: potential basis for biological activity. 1560 40