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)

We examined effects of three structurally related pyridinium compounds, 1-methyl-4-phenylpyridinium (MPP+), paraquat, and 1-methyl-4-(4'-nitrophenyl) pyridinium (analog 1), on the energy metabolism in pheochromocytoma PC12 cells. MPP+ inhibited the intracellular NADH oxidation by the mitochondrial respiratory chain, judging from the decrease of the cytosolic NAD+/NADH ratio. Paraquat enhanced the oxidation of NADH and decreased intracellular ATP more than MPP+. The inhibition of the mitochondrial respiration by MPP+ was partially compensated by enhanced glycolysis, while paraquat inhibited glycolysis at the level of hexokinase probably due to the intracellular production of oxygen radicals. Analog 1 moderately enhanced glycolysis, moderately increased a cytosolic ratio of NAD+/NADH, and caused only a slight decline of intracellular ATP. Paraquat was the most cytotoxic of the three compounds. Thus, the three structurally related compounds, MPP+, paraquat, and analog 1, showed different effects on the mitochondrial respiratory chain and the glycolytic pathway in PC 12 cells. Their properties found in the cells well reflected those obtained by using bovine heart submitochondrial particles.
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PMID:Changes of energy metabolism induced by 1-methyl-4-phenylpyridinium (MPP+)-related compounds in rat pheochromocytoma PC12 cells. 899 Feb 70

A 1532-base pair 5'-flanking region of the gene encoding rat type III hexokinase has been cloned and sequenced. The total sequence includes positions -1548 to -17 (A of the translational start ATG as position +1). Using luciferase reporter constructs transfected into PC12 (rat pheochromocytoma) and L2 (rat lung) cells, basal promoter activity has been associated with sequence between -182 and -89. This includes a single transcriptional start site, an adenine at position -134 identified by primer extension. Together with previously cloned cDNA sequence, this accounts for an mRNA of approximately 3.9 kilobases, found by Northern blotting of RNA from rat lung and kidney. Sequence upstream of the transcriptional start site was devoid of canonical TATA and CAAT elements. An octamer 1 (Oct-1) binding site, located between positions -166 and -159 was shown by deletion analysis and site-directed mutation to be critical for promoter activity. Nuclear extracts from PC12 cells contained a protein (or proteins) specifically binding the octamer sequence, and supershift experiments with anti-Oct-1 indicated involvement of this ubiquitously expressed transcription factor in the complex. Sequence including the Oct-1 site and immediately adjacent regions was protected from DNase I digestion in footprinting experiments with nuclear extracts from PC12 cells. Reverse transcription polymerase chain reaction indicated that levels of type III hexokinase mRNA in rat tissues increased in the order brain < liver < lung approximately kidney; immunoblotting indicated that type III hexokinase protein in these tissues increased in a similar manner.
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PMID:Characterization of the rat type III hexokinase gene promoter. A functional octamer 1 motif is critical for basal promoter activity. 1053 80