Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oxyR regulon plays a central role in the defense of Escherichia coli against the endogenous oxidative damage associated with active aerobic growth. Here we have studied the transcriptional regulation of oxyR in E. coli growing aerobically in rich medium. Expression of a single-copy oxyR'::lacZ reporter construct varied sixfold along the growth curve, with the highest value at 4 to 6 h of growth (approximately 14 x 10(8) cells x ml(-1)). Direct measurements of oxyR mRNA by primer extension showed the same biphasic expression but with a peak somewhat earlier in cell growth (2 to 3 h; approximately 3.5 x 10(8) cells x ml(-1)). The results of immunoblotting experiments demonstrated that the level of OxyR protein exhibits the same biphasic expression. Mutant strains lacking adenylate cyclase (cya) or Crp protein (crp) failed to increase oxyR expression during exponential growth. On the other hand, an rpoS mutation allowed oxyR expression to continue increasing as the cells entered stationary phase. Consistent with a biological role for increased levels of OxyR during exponential growth, the crp cya strain had lower activities of catalase hydroperoxidase I and glutathione reductase and an increased sensitivity to exogenously added hydrogen peroxide. These results suggest that the Crp-dependent upregulation of oxyR in exponential phase is a component of a multistep strategy to counteract endogenous oxidative stress in actively growing E. coli cells.
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PMID:Transcriptional regulation of the Escherichia coli oxyR gene as a function of cell growth. 932 69

Preliminary clinical trials have recently shown that phenytoin, an antiepileptic drug, may also be beneficial for treatment of bipolar disorder. To examine molecular mechanisms of action of phenytoin as a potential mood stabilizer, DNA microarrays were used to study the effect of phenytoin on gene expression in the hippocampus and frontal cortex of Sprague-Dawley rats. While our particular interest is in bipolar disorder, this is the first DNA microarray study on the effect of phenytoin in brain tissue, in general. As compared with control rats, treated rats had 508 differentially expressed genes in the hippocampus and 62 in the frontal cortex. Phenytoin modulated the expression of genes which may affect neurotransmission, e.g. glutamate decarboxylase 1 (Gad1) and gamma-aminobutyric acid A receptor, alpha 5 (Gabra5). Phenytoin also exerted an effect on neuroprotection-related genes, namely the survival-promoting and antioxidant genes v-akt murine thymoma viral oncogene homolog 1 (Akt1), FK506 binding protein 12-rapamycin associated protein 1 (Frap1), glutathione reductase (Gsr) and glutamate cysteine ligase catalytic subunit (Gclc). The expression of genes potentially associated with mechanisms of mood regulation such as adenylate cyclase-associated protein 1 (Cap1), Glial Fibrillary Acidic Protein (Gfap) and prodynorphin (Pdyn) was also altered. Some of the above genes are regarded as targets of classical mood stabilizers and their modulation supports the clinical observation that phenytoin may have mood-stabilizing effects. The results may provide new insights regarding the mechanism of action of phenytoin and genes found differentially expressed following phenytoin administration may play a role in the pathophysiology of either bipolar disorder or epilepsy.
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PMID:Effect of prolonged phenytoin administration on rat brain gene expression assessed by DNA microarrays. 2041 26