Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of both bovine adrenodoxin (ADX) and NADPH-adrenodoxin reductase (ADR) were examined in Saccharomyces cerevisiae. Three ADX and two ADR expression plasmids were constructed by inserting each of the corresponding cDNA fragments between the yeast alcohol dehydrogenase I promoter and terminator of the expression vector pAAH5N. Plasmids pAX and pMX contained the coding region for the precursor and mature ADX, respectively, while pCMX carried the mature ADX preceded by the mitochondrial signal of yeast cytochrome c oxidase subunit IV (COX IV). Similarly, pMR and pCMR coded for mature ADR without and with the mitochondrial signal of yeast COX IV, respectively. Transformed S. cerevisiae AH22[rho 0]/pAX cells produced the ADX precursor, while AH22[rho 0]/pMX and AH22[rho 0]/pCMX cells produced mature ADX (mat-ADX) and modified ADX (mat-COX/ADX), respectively. Mat-ADX and mat-COX/ADX were found mainly in the cytosolic and mitochondrial fractions, respectively, and showed cytochrome c reductase activity. AH22[rho+]/pMR and AH22[rho+]/pCMR cells produced mature ADR (mat-ADR) and modified ADR (mat-COX/ADR), respectively. Mat-ADR lacking the mitochondrial signal was found in the cytosolic fraction and exhibited cytochrome c reductase activity, while mat-COX/ADR was localized in the mitochondrial fraction, but showed no reductase activity. In an in vitro reconstituted system consisting of both mat-COX/ADX- and mat-ADR-containing fractions, bovine P450scc converted cholesterol into pregnenolone. Thus mat-COX/ADX and mat-ADR produced in the yeast can transfer electrons from NADPH to P450scc.
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PMID:Expression of bovine adrenodoxin and NADPH-adrenodoxin reductase cDNAs in Saccharomyces cerevisiae. 193 Jun 96

Amyloid-beta peptide (Abeta) binding alcohol dehydrogenase (ABAD), an enzyme present in neuronal mitochondria, is a cofactor facilitating Abeta-induced cell stress. We hypothesized that ABAD provides a direct link between Abeta and cytotoxicity via mitochondrial oxidant stress. Neurons cultured from transgenic (Tg) mice with targeted overexpression of a mutant form of amyloid precursor protein and ABAD (Tg mAPP/ABAD) displayed spontaneous generation of hydrogen peroxide and superoxide anion, and decreased ATP, as well as subsequent release of cytochrome c from mitochondria and induction of caspase-3-like activity followed by DNA fragmentation and loss of cell viability. Generation of reactive oxygen species (ROS) was associated with dysfunction at the level of mitochondrial complex IV (cytochrome c oxidase, or COX). In neurons cultured from Tg mAPP/ABAD mice, COX activity was selectively decreased, and cyanide, an inhibitor of complex IV, exacerbated leakage of ROS, induction of caspase-3-like activity, and DNA fragmentation. In vivo, Tg mAPP/ABAD mice displayed reduced levels of brain ATP and COX activity, diminished glucose utilization, as well as electrophysiological abnormalities in hippocampal slices compared with Tg mAPP mice. In contrast, neither Tg ABAD mice nor nontransgenic (non-TG) littermates showed similar changes in ATP, COX activity, glucose utilization or electrophysiological properties. Each of the genotypes (Tg ABAD, Tg mAPP and Tg mAPP/ABAD mice, and non-TG littermates) displayed normal reproductive fitness, development and lifespan (1) These findings link ABAD-induced oxidant stress to critical aspects of Alzheimer's disease (AD)-associated cellular dysfunction, suggesting a pivotal role for this enzyme in the pathogenesis of AD.
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PMID:ABAD enhances Abeta-induced cell stress via mitochondrial dysfunction. 1566 36

The increasing number of diagnosed breast lesions lead to the critical need for new markers that would elucidate the process of tumorigenesis. The objective of the study was to examine COX-2, p16, and Ki67 expression in a broad spectrum of breast lesions in order to define the proteins' phenotype throughout the tumorigenesis. Expression was studied by immunohistochemistry in 308 human breast samples divided into 7 subgroups - flat epithelial atypia (FEA), atypical hyperplasia (ADH), intraductal carcinoma (DCIS), invasive cancer (IC), benign lesions (BLs), normal tissue adjacent to breast cancer (CANT), and fatty tissue (FT). Analysis among 4 subgroups - premalignant lesions (DIN), IC, BLs, and normal tissue was also performed. High prevalence of COX-2 overexpression was found in all breast lesions including BLs (70% FEA, 89% ADH, 86% DCIS, 81% IC, 44% CANT, 92% BLs, 29% FT). Significant dominance of p16 overexpression was found in premalignant lesions and BLs (50% FEA, 67% ADH, 50% DCIS, 37% IC, 8% CANT, 58% BLs, 21% FT). The location of staining within p16+ cells differed - BLs showed nuclear positivity, whereas in IC it was exclusively cytoplasmic. Premalignant lesions showed all types of p16 positivity. Significantly higher prevalence of COX-2+p16+Ki67+ phenotype was in premalignant tumors with the highest prevalence in ADH (40% of FEA, 67% ADH, 35% DCIS, 20% IC, 3% CANT, 20% BLs, 14% FT). Our observations showed a high prevalence of COX-2+p16+Ki67+ phenotype in premalignant lesions. Further studies are needed in order to elucidate if this phenotype reflects any specific pathway of future progression of premalignant breast lesions.
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PMID:Expression of COX-2, p16, and Ki67 in the range from normal breast tissue to breast cancer. 3314 51