Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver alcohol dehydrogenase oxidizes ethanol to acetaldehyde, which is further oxidized to acetate by aldehyde dehydrogenase-2 (ALDH2*1). Individuals who carry a low-activity ALDH2 (ALDH2*2) display high blood acetaldehyde levels after ethanol consumption, which leads to dysphoric effects, such as facial flushing, nausea, dizziness, and headache ("Asian alcohol phenotype"), which result in an aversion to alcohol and protection against alcohol abuse and alcoholism. Mimicking this phenotype may reduce alcohol consumption in alcoholics. RNA interference (RNAi) is a cell process in which a short interfering RNA (siRNA) of 21-25 bp guides the degradation of a complementary target mRNA. Thus, siRNAs may be useful in mimicking the Asian phenotype by inhibiting ALDH2 gene expression. We determined the inhibitory effect of three chemically synthesized siRNAs targeted against rat ALDH2 mRNA in human embryonic kidney cells (HEK-293 cell lines) transfected with a plasmid carrying the rat ALDH2 cDNA. Two of the three siRNAs were active, yielding a 65-75% reduction of ALDH2 activity. Based on the most promising siRNA sequence, three short hairpin RNA (shRNA) genes driven by the human U6 RNA promoter were designed and cloned in a plasmid. After transfection of HEK-293 cells, one of the genes was shown to be active, yielding a 50% reduction of ALDH2 activity. This effect is consistent with a 50% reduction in ALDH2 mRNA, whereas neither beta-actin mRNA nor the interferon-inducible transmembrane protein-1 mRNA levels were affected. This study describes chemically synthesized siRNAs and an endogenously synthesized shRNA, which reduce ALDH2 activity and constitute tools that should be of value for further alcohol research.
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PMID:RNA interference against aldehyde dehydrogenase-2: development of tools for alcohol research. 1925 Nov 11

Surface-imprinted polymers allow for specific cell detection based on simultaneous recognition of the cell shape, cell size, and cell membrane functionalities by macromolecular cell imprints. In this study, the specificity of detection and the detection sensitivity for target cells within a pool of non-target cells were analyzed for a cell-specific surface-imprinted polymer combined with a heat-transfer-based read-out technique (HTM). A modified Chinese hamster ovarian cell line (CHO-ldlD) was used as a model system on which the transmembrane protein mucin-1 (MUC1) could be excessively expressed and for which the occurrence of MUC1 glycosylation could be controlled. In specific cancer cells, the overexpressed MUC1 protein typically shows an aberrant apical distribution and glycosylation. We show that surface-imprinted polymers discriminate between cell types that (1) only differ in the expression of a specific membrane protein (MUC1) or (2) only differ in the membrane protein being glycosylated or not. Moreover, surface-imprinted polymers of cells carrying different glycoforms of the same membrane protein do target both types of cells. These findings illustrate the high specificity of cell detection that can be reached by the structural imprinting of cells in polymer layers. Competitiveness between target and non-target cells was proven to negatively affect the detection sensitivity of target cells. Furthermore, we show that the detection sensitivity can be increased significantly by repetitively exposing the surface to the sample and eliminating non-specifically bound cells by flushing between consecutive cell exposures.
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PMID:Heat-transfer resistance measurement method (HTM)-based cell detection at trace levels using a progressive enrichment approach with highly selective cell-binding surface imprints. 2460 12