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)

The Fas ligand induces apoptosis in activated immunocytes that express the Fas receptor. Fas-ligand transcripts have been found previously in murine intestine but the intestinal tissues that express Fas ligand have not been identified. We used immunohistochemistry to examine the expression of the Fas ligand in the enteric nervous system of rats, mice, guinea-pigs, ferrets and humans. Fas-ligand immunoreactivity was detectable in enteric nerve fibres and neurons in all species tested, representing 25%-50% of the neurons in rats, mice and guinea-pigs. An antigen of approximately 48 kDa was detected by Western blot analysis with Fas-ligand antiserum in the dissected enteric plexuses of duodenum from a C3H/HeJ mouse. In gld mice that harbour a Fas-ligand mutation, Fas-ligand immunoreactivity was slightly more intense in neurons and fibres and was also apparent in submucosal lymphocytes. In the myenteric plexuses of guinea-pig ileum and human colon, Fas-ligand immunoreactivity was not contained in neurons exhibiting nicotinamide-adenine dinucleotide phosphate-diaphorase activity. In the submucosal plexus of guinea-pig ileum, labelled neurons included some neuropeptide-Y-containing neurons but none with vasoactive intestinal polypeptide. We conclude that the Fas ligand is expressed by a large subset of enteric neurons and may provide the basis for cytotoxic neuroimmune interactions in the intestines.
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PMID:Immunoreactivity for the Fas ligand in the mammalian enteric nervous system. 937 38

The mechanisms of injury- and disease-related degeneration of motor neurons (MNs) need clarification. Unilateral avulsion of the sciatic nerve in the mouse induces apoptosis of spinal MNs that is p53 and Bax dependent. We tested the hypothesis that MN apoptosis is Fas death receptor dependent and triggered by nitric oxide (NO)- and superoxide-mediated damage to DNA. MNs in mice lacking functional Fas receptor and Fas ligand were protected from apoptosis. Fas protein levels and cleaved caspase-8 increased in MNs after injury. Fas upregulation was p53 dependent. MNs in mice deficient in neuronal NO synthase (nNOS) and inducible NOS (iNOS) resisted apoptosis. After injury, MNs increased nNOS protein but decreased iNOS protein; however, iNOS contributed more than nNOS to basal and injury-induced levels of NADPH diaphorase activity in MNs. NO and peroxynitrite (ONOO-) fluorescence increased in injured MNs, as did nitrotyrosine staining of MNs. DNA damage, assessed as 8-hydroxy-2-deoxyguanosine and single-stranded DNA, accumulated within injured MNs and was attenuated by nNOS and iNOS deficiency. nNOS deficiency increased DNA repair protein oxoguanine DNA-glycosylase, whereas iNOS deficiency blocked diaphorase activity. MN apoptosis was blocked by the antioxidant Trolox and by overexpression of wild-type human superoxide dismutase-1 (SOD1). In contrast, injured MNs in mice harboring mutant human SOD1 had upregulated Fas and iNOS, escalated DNA damage, and accelerated and increased MN degeneration and underwent necrosis instead of apoptosis. Thus, adult spinal MN apoptosis is mediated by upstream NO and ONOO- genotoxicity and downstream p53 and Fas activation and is shifted to necrosis by mutant SOD1.
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PMID:Adult motor neuron apoptosis is mediated by nitric oxide and Fas death receptor linked by DNA damage and p53 activation. 1600 Jun 35

One pathogenic mechanism of ethanol-induced liver injury is the excessive production of reactive oxygen species (ROS), which may result in alcoholic liver disease (ALD) characterized by cell death due to necrosis and apoptosis. Taurine was proved to protect against liver damage. However, whether taurine attenuates ethanol-induced hepatic apoptosis remains unknown. The present study aims to elucidate this effect and its underlying mechanism. Taurine was administered to ALD rats and an in vitro experiment in which taurine was added to primary rat hepatocytes cultured with ethanol was conducted. Mitochondrial function and anti-oxidative capacity of the liver were tested. TUNEL and AO-EB double staining were conducted to detect apoptosis of liver cells. Expressions of factors and proteins involved in mitochondrial and death receptor pathways were detected by RT-PCR and Western-blot. The results showed that taurine inhibited the decline of cell functions and apoptosis in hepatocytes cultured with ethanol. Furthermore, increased malondialdehyde (MDA) and reduced superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), cytochrome c oxidase (COX) and NADH dehydrogenase (ND) in ALD rats were mediated by taurine. RT-PCR and western-blot results revealed that taurine down-regulated expression of Bax, Fas, Fas ligand (FasL), caspase 3 and caspase 9 while up-regulating the expression of Bcl-2 in ethanol-cultured hepatocytes. In summary, taurine inhibit ethanol-induced hepatic apoptosis by regulating mitochondrial or death receptor pathways.
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PMID:Taurine prevents ethanol-induced apoptosis mediated by mitochondrial or death receptor pathways in liver cells. 2962