Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypoxic cells in solid tumors are known to be resistant to radiation, and may also be resistant to some anti-cancer drugs. Biochemical properties of hypoxic cells, such as their dependence on anaerobic glycolysis leading to production of lactate and low pH might have potential for inhibition by drugs with selective activity against hypoxic cells. Such drugs might improve the Therapeutic Index when used with radiation or some conventional anti-cancer drugs. Preliminary studies have shown that the combination of hypoxia and low pH (pH 6.5-6.0) was cytotoxic to Chinese Hamster Ovary (CHO) cells incubated in vitro for up to 6 hours, although neither factor alone reduced plating efficiency. Lonidamine, an inhibitor of mitochondrially-bound hexokinase and lactate transport, was cytotoxic to CHO cells at low pH, but had no effect at physiological pH under aerobic or hypoxic conditions. Lonidamine has also been tested for in vivo effects against three murine tumors: the KHT fibrosarcoma, 16/C mammary carcinoma and the Lewis Lung Tumor. The drug was tested either alone, or with radiation or Adriamycin to kill aerobic cells, and/or with glucose and insulin to lower intra-tumor pH. No major therapeutic effects have been demonstrated.
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PMID:The effect of the drug lonidamine on Chinese hamster ovary cells in vitro and on experimental tumors. 648 Apr 46

In cystic fibrosis, the mutation of the CFTR protein causes reduced transepithelial Cl(-) secretion. As recently proposed, beside its role of Cl(-) channel, CFTR may regulate the activity of other channels such as a Ca(2+)-activated Cl(-) channel. Using a calcium imaging system, we show, in adenovirus-CFTR infected Chinese Hamster Ovary (CHO) cell monolayers, that CFTR can act as a regulator of intracellular [Ca(2+)](i) ([Ca(2+)](i)), involving purino-receptors. Apical exposure to ATP or UTP produced an increase in ([Ca(2+)](i) in noninfected CHO cell monolayers (CHO-WT), in CHO monolayers infected with an adenovirus-CFTR (CHO-CFTR) or infected with an adenovirus-LacZ (CHO-LacZ). The transient [Ca(2+)](i) increase produced by ATP or UTP could be mimicked by activation of CFTR with forskolin (20 microm) in CHO-CFTR confluent monolayers. However, forskolin had no significant effect on [Ca(2+)](i) in noninfected CHO-WT or in CHO-LacZ cells. Pretreatment with purino-receptor antagonists such as suramin (100 microm) or reactive blue-2. (100 microm), and with hexokinase (0.28 U/mg) inhibited the [Ca(2+)](i) response to forskolin in CHO-CFTR infected cells. Taken together, our experiments provide evidence for purino-receptor activation by ATP released from the cell and regulation of [Ca(2+)](i) by CFTR in CHO epithelial cell membranes.
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PMID:Regulation of intracellular Ca(2+) by CFTR in Chinese hamster ovary cells. 1050 33

Glycosylation-deficient Chinese Hamster Ovary (CHO) cell lines can be used to expand our understanding of N-glycosylation pathways and to study Congenital Disorders of Glycosylation, diseases caused by defects in the synthesis of N-glycans. The mammalian N-glycosylation pathway involves the step-wise assembly of sugars onto a dolichol phosphate (P-Dol) carrier, forming a lipid-linked oligosaccharide (LLO), followed by the transfer of the completed oligosaccharide onto the protein of interest. In order to better understand how deficiencies in this pathway affect the availability of the completed LLO donor for use in N-glycosylation, we used a non-radioactive, HPLC-based assay to examine the intermediates in the LLO synthesis pathway for CHO-K1 cells and for three different glycosylation-deficient CHO cell lines. B4-2-1 cells, which have a mutation in the dolichol phosphate-mannose synthase (DPM2) gene, accumulated LLO with the structure Man(5)GlcNAc(2)-P-P-Dol, while MI8-5 cells, which lack glucosyltransferase I (ALG6) activity, accumulated Man(9)GlcNAc(2)-P-P-Dol. CHO-K1 and MI5-4 cells both produced primarily the complete LLO, Glc(3)Man(9)GlcNAc(2)-P-P-Dol, though the relative quantity was lower in MI5-4. MI5-4 cells have reduced hexokinase activity which could affect the availability of many of the substrates required for LLO synthesis and, consequently, impair production of the final LLO donor. Increasing hexokinase activity by overexpressing hexokinase II in MI5-4 caused a decrease in the relative quantities of the incomplete LLO intermediates from Man(5)GlcNAc(2)-PP-Dol through Glc(1)Man(9)GlcNAc(2)-PP-Dol, and an increase in the relative quantity of the final LLO donor, Glc(3)Man(9)GlcNAc(2)-P-P-Dol. This study suggests that metabolic engineering may be a useful strategy for improving LLO availability for use in N-glycosylation.
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PMID:Analysis and metabolic engineering of lipid-linked oligosaccharides in glycosylation-deficient CHO cells. 2033 63