Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.1 (NADPH-diaphorase)
 3,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Administration of inhibitors of neuronal nitric oxide synthase or deletion of the encoding gene in rodents provided evidence that neuronal nitric oxide synthase activity may contribute to neuronal cell death following global and focal cerebral ischemia. In the present study, we investigated by in situ hybridization the expression of an endogenous inhibitor of neuronal nitric oxide synthase activity, designated protein inhibitor of neuronal nitric oxide synthase and homologous to cytoplasmic dynein light chain, in the post-ischemic rat brain. Following global ischemia induced by cardiac arrest, messenger RNA expression of protein inhibitor of neuronal nitric oxide synthase was rapidly induced in pyramidal neurons of the hippocampal CA3 region and granule cell of the dentate gyrus which are resistant to ischemic damage. In vulnerable CA1 pyramidal neurons however, protein inhibitor of neuronal nitric oxide synthase expression remained at basal level after global ischemia and was associated with an increase in nicotinamide adenine dinucleotide phosphate-diaphorase activity and subsequent DNA fragmentation indicating ischemia-mediated neuronal cell death. Following focal cerebral ischemia induced by permanent occlusion of the middle cerebral artery, transcripts of protein inhibitor of neuronal nitric oxide synthase progressively accumulated in cortical neurons bordering the infarct area. After transient middle cerebral artery occlusion however, messenger RNA levels of protein inhibitor of neuronal nitric oxide synthase increased in the reperfused neocortex. Our findings indicate that cerebral ischemia leads to an increase in neuronal expression of protein inhibitor of neuronal nitric oxide synthase in brain regions where sustained or "uncoupled" nitric oxide synthase activity may be detrimental to neurons. Lack of post-ischemic induction of protein inhibitor of neuronal nitric oxide synthase in CA1 pyramidal neurons may result in high nitric oxide synthase activity after global ischemia and could contribute to delayed neuronal cell death.
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PMID:Induction of protein inhibitor of neuronal nitric oxide synthase/cytoplasmic dynein light chain following cerebral ischemia. 952 64

The protein inhibitor of neuronal nitric oxide synthase (PIN) performs critical functions in several biological processes including inhibition of neuronal nitric oxide synthase (nNOS) activity, intracellular trafficking of proteins and cellular maturation. In this study, we isolated a gene that putatively encoded a PIN homologue in the Taenia solium metacestode (TsM), a causative agent for neurocysticercosis (NC). A full-length cDNA of 452-bp in length, designated TsMPIN, was found to encode an open reading frame (ORF) of 103 amino acids with a predicted molecular weight of 11.3kDa. This single copy gene possessed an intervening short intron (74bp-long) within its ORF region. The deduced amino acid sequence revealed a substantial degree of sequence identity with the PINs and the dynein light-chains isolated from other organisms (63-81%). TsMPIN ectopically expressed in neuroblastoma N1E115 cells effectively inhibited dimerization of nNOS upon stimulation. The recombinant TsMPIN also negatively regulated the dimerization of recombinant nNOS, which was attenuated significantly by the TsMPIN-specific antibody. TsMPIN was primarily localized in the lining cells of the trabecules and the muscles surrounding the scolex, and was sparsely within the cytosol of the bladder wall. We also identified TsM nNOS-immunoreactive protein by both NADPH-diaphorase histochemical staining, and immunohistochemical localization and immunoprecipitation with antibodies specific to nNOS N-terminus. These two functionally related proteins showed a co-localized expression pattern. Our results strongly suggest that the production of NO in the TsM might be tightly regulated through the nNOS-TsMPIN feedback system to maintain physiological homeostasis in the parasite.
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PMID:Functional identification of a protein inhibitor of neuronal nitric oxide synthase of Taenia solium metacestode. 1709 1