Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mouse liver microsomes were solubilized in various detergent systems, and the resulting aggregate structures associated with cytochrome P-450, cytochrome c reductase, and UDP glucuronosyltransferase were sized by gel filtration chromatography. Cholate or its derivative, CHAPS, in combination with Emulgen 911 or Lubrol 12A9 were necessary to generate a particle of about 140 k daltons, the smallest structure associated with cytochrome P-450. Cholate or CHAPS alone was sufficient to generate a minimally sized aggregate of 200 k daltons associated with NADPH cytochrome c reductase activity. Cholate in combination with Emulgen 911 or Lubrol 12A9 generated particles of about 280 k daltons associated with UDP glucuronosyltransferase activity. CHAPS alone also generated similarly sized particles under conditions in which UDP glucuronosyltransferase activity toward 1-naphthol and morphine was two to about twenty times greater, respectively, than with the combination of detergents. This finding suggests that the zwitterionic CHAPS is superior to other detergent systems for studies concerned with the purification of transferase enzymes, a microsomal system in which investigation of the number of different forms has been hampered by the instability of the enzyme upon solubilization and subsequent manipulation.
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PMID:Effect of different detergent systems on the molecular size of UDP glucuronosyltransferase and other microsomal drug-metabolizing enzymes. 643 Dec 26

The barrier functions in epithelial and endothelial cells seem to be very important for maintaining normal biological homeostasis. However, it is unclear whether or how bile acids affect the epithelial barrier. We examined the bile acid-induced disruption of the epithelial barrier. We measured the transepithelial electrical resistance (TEER) of Caco-2 cells as a marker of disruption of the epithelial barrier. Reactive oxygen species (ROS) generation was also measured. Cholic acid (CA) decreased the TEER and increased intracellular ROS generation. PLA2 (phospholipase A2), COX (cyclooxygenase), PKC (protein kinase), ERK 1/2 (extracellular signal-regulated kinase 1/2), PI 3 K (phosphatidylinositol 3-kinase), p38 MAPK (p38 mitogen-activated protein kinase), MLCK (myosin light-chain kinase), NADH dehydrogenase, and XO (xanthine oxidase) inhibitors or ROS scavengers prevented the CA-induced TEER decrease. PLA2, COX, PKC, NADH dehydrogenase, and XO inhibitors prevented the CA-induced ROS generation but not ERK 1/2, PI 3 K, p38 MAPK, and MLCK inhibitors. If the cells were treated with ROS generators such as superoxide dismutase, the TEER decreased. ERK 1/2, PI 3 K, p38 MAPK, and MLCK inhibitors prevent these ROS generators from inducing the TEER decrease. These results suggest that ROS play an important role. In addition, PLA2, COX, PKC, NADH dehydrogenase, and XO are located upstream of the ROS generation, but ERK 1/2, PI 3 K, p38 MAPK, and MLCK are downstream during the signaling of CA-induced TEER alterations.
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PMID:Bile acid modulates transepithelial permeability via the generation of reactive oxygen species in the Caco-2 cell line. 1610 7