Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.5 (NADH dehydrogenase)
 2,135 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of novel genes that are up-regulated in diabetic kidneys have been identified. Recently, transforming growth factor-beta (TGF-beta)--driven secreted proteins, i.e., connective tissue growth factor (CTGF) and gremlin, were identified. They are up-regulated in kidneys of diabetic animals and modulate the biology of mesangial cells. CTGF mediates TGF-beta--induced matrix overproduction by the mesangial cells. Gremlin is a putative antagonist of bone morphogenetic protein-2 that blocks mesangial cell proliferation. Thus, gremlin may modulate the biology of mesangium by stimulating mesangial cell proliferation and in turn production of matrix. In addition, transcriptionally regulated kinases, serum glucocorticoid-regulated kinase and munc-13 have been identified. The former stimulates renal tubular Na+ transport and is involved in hyperfiltraion of diabetic kidneys by a Na+ transport feedback mechanism. Munc-13 has been shown to induce apoptosis in hyperglycemic state via diacylglycerol-activated, PKC-independent signaling pathway. Another pathway relevant to diabetic nephropathy is polyol pathway, where glucose is reduced to sorbitol by aldose reductase. Recently, a renal-specific reductase of the aldo-keto reductase family was isolated. It is up-regulated in diabetic mice, and this could serve as a suitable target for gene therapy in renal complications of diabetes. Several mitochondrial genome-encoded genes, such as, cytochrome oxidase and NADH dehydrogenase, are up-regulated in diabetic kidneys. A novel nuclear-encoded mitochondrial gene, i.e., translocase inner mitochondrial membrane 44 (Tim44), is up-regulated in diabetic kidneys, and it may also serve as another target for molecular therapeutic intervention at the core storage energy sites, i.e., mitochondria. In this review, these novel differentially regulated genes that respond to hyperglycemic stress are described, and they may serve as possible targets for gene therapy in the treatment of diabetic nephropathy.
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PMID:Gene expression and identification of gene therapy targets in diabetic nephropathy. 1184 17

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

A bush-type plant was selected from tropical pumpkin 'cga' (Cucurbita moschata Duchesne) in order to study the vine development in C. moschata. In this study, a novel gene encoding NADH dehydrogenase was isolated from the vine line (cgaV) of C. moschata, that was not expressed in the near isogenic bush line (cgaBu). This gene, designated as CmV1 (C. moschata vine 1), was 545 bp in length and was composed of a 477 bp open reading frame, which had 99% nucleotide similarity to the chloroplast ndhJ gene for NADH dehydrogenase subunit J from Brassica oleracea. The deduced amino acid sequence of CmV1 had 99% similarity to NADH dehydrogenase subunit J from Arabidopsis and had 98% similarity to NADH dehydrogenase subunit from Barbarea verna. Analysis of the basic characteristics of the CmV1 protein revealed that it has one Respiratory chain NADH dehydrogenase 30 kD subunit signature, three N-myristoylation sites, one Casein kinase II phosphorylation site, and one Protein kinase C phosphorylation site. Reverse transcriptase-PCR analysis showed that CmV1 was expressed at a high level in the internodes and hypocotyls and was expressed stronger in elongating internodes than in fully expanded internodes. In conclusion, results obtained in the present study suggest that CmV1 gene might play important roles in vine elongation of tropical pumpkin.
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PMID:Molecular cloning and expression of a bush related CmV1 gene in tropical pumpkin. 1930 73