Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because of the limited availability of human tissues, leukemia cell lines are often utilized as the models for human leukocytes. In this study, we investigated the NADPH-dependent reductases and polyol pathway in commonly utilized human leukemia cell lines. The relative amounts of aldose and aldehyde reductases were estimated by separating two enzymes with chromatofocusing. The flux of glucose through the polyol pathway was examined by 19F-NMR using 3-fluoro-3-deoxy-D-glucose (3FG) as substrate. Sugar alcohol analysis was conducted by gas chromatography. In myelocytic leukemia cells, the major reductase was aldehyde reductase, and levels of aldose reductase were extremely low. Although lymphocytic cells also contained both aldose and aldehyde reductases, the levels of aldose reductase appeared to be higher in lymphocytic cells than myeolcytic cells. In two lymphocytic cells MOLT-4 and SKW6.4, aldose reductase is clearly dominant. When incubated in medium containing D-galactose, all cell lines quickly accumulated galactitol. There was correlation between galactitol levels and aldose reductase levels. The aldose reductase inhibitor FK 366 significantly reduced the formation of galactitol. 19F-NMR of the cells cultured with 3FG as substrate demonstrated the formation of 3-fluoro-3-dexoy-sorbitol in all the cell lines examined in this study. The relative amounts of sorbitol and fructose varied significantly among the cells. The data confirm that the polyol pathway is present in both myelocytic and lymphocytic leukemia cell lines. However, there is a large variation among the cell lines in the levels of enzymes and flux of glucose through the polyol pathway.
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PMID:NADPH-dependent reductases and polyol formation in human leukemia cell lines. 1260 23

Human zinc-fingers and homeoboxes (ZHX) 1, a transcriptional repressor, was originally cloned as an interacting protein with the activation domain of the A subunit of nuclear factor-Y (NF-YA). As the first step in investigating the mechanism by which ZHX1 acts as a transcriptional repressor, we conducted a search of ZHX1-interacting proteins using a yeast two-hybrid system. Nuclear proteins such as ZHX1, transcriptional co-factors and DNA-binding proteins, zyxin, androgen-induced aldose reductase and eleven-nineteen lysine-rich leukaemia gene, as well as some unknown proteins, were cloned. Molecular cloning and determination of the nucleotide sequence of the full-length cDNA encoding a novel protein revealed that it consists of 956 amino acid residues and contains two zinc-finger (Znf) motifs and five homeodomains (HDs) as well as ZHX1. We concluded that the protein forms the ZHX family with ZHX1 and denoted it ZHX3. ZHX3 not only dimerizes with both ZHX1 and ZHX3, but also interacts with the activation domain of the NF-YA. Further analysis revealed that ZHX3 is a ubiquitous transcriptional repressor that is localized in nuclei and functions as a dimer. Lastly, the dimerization domain, the interaction domain with NF-YA, and the repressor domain are mapped to a region including the HD1 region, and two nuclear localization signals are mapped to the N-terminal through Znf1 and the HD2 region, respectively.
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PMID:Analysis of zinc-fingers and homeoboxes (ZHX)-1-interacting proteins: molecular cloning and characterization of a member of the ZHX family, ZHX3. 1265 32