Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.13.3 (histidine kinase)
 2,405 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hexokinase plays an important role in glucose-utilizing tissues like normal brain and cancers. In these tissues, hexokinase (HK) is mainly bound to mitochondria (mHK). Our objectives were to evaluate total HK (tHK) activity and mHK fraction in gliomas and to determine whether mHK binding could be targeted for therapy. Tumors were obtained from 26 patients and 13 were xenografted. HK, lactate and ATP were measured in cytosol and mitochondria extracts. The tHK expressed in mU/mg protein were 147 +/- 19 and 78 +/- 12, in fresh gliomas and xenografts, respectively, and of 489 in the normal brain. The mHK fraction was 76% in normal brain, 74 +/- 4% in fresh tumors and 53 +/- 6% in xenografts. Lactate/mHK ratios were higher in gliomas than in normal brain. The ATP was 10, 52 +/- 31 and 19 +/- 8 nmol/mg protein in normal brain, xenografts and fresh gliomas respectively. Loss of one copy of chromosome 10 which carries the HK1 gene, was evidenced in 11 of the 13 xenografted gliomas. The anti-tumor effect of lonidamine (LND), which affects glycolysis in interfering with mHK activity, was tested in nude mice bearing 4 gliomas. LND (125 mg/kg, given i.p., twice daily for 5 days) led to a growth inhibition of TG-7-RO of 72%, with 2-fold growth retardation, and had no effect for TG-8-OZ. Intermediate LND-sensitivities for TG-11-DU and TG-10-PY were noted. The LND-sensitivity was correlated with the mHK activity (R2 = 0.73) and mHK fraction (R2 = 0.88). HK binding to mitochondria is a key of glycolysis in malignant gliomas, and targetting this binding with appropriate agents could be an effective therapeutic approach.
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PMID:Mitochondria-bound hexokinase as target for therapy of malignant gliomas. 762 99

Lactic acid bacteria are widely used in industrial fermentation. The potential use of these bacteria as homologous and heterologous protein expression hosts has been investigated extensively. The NIsin-Controlled gene Expression system (the NICE system) is an efficient and promising gene expression system based on the autoregulation mechanism of nisin biosynthesis in the Lactococcus lactis. In the NICE system, the membrane-located histidine kinase NisK senses the inducing signal nisin and autophosphorylates, then transfers phosphorous group to intracellular response regulator protein NisR which activates nisA promoter to express the downstream gene(s). The NICE system allows regulated overproduction of a variety of interest proteins by several Gram-positive bacteria, especially L. lactis. The essential elements for system construction, its application for expression of some biotechnologically important proteins and further improvements of this system are discussed.
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PMID:The nisin-controlled gene expression system: construction, application and improvements. 1638 Feb 25