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

Transforming growth factors beta (TGF-beta), a family of pleiotropic cytokines, are widely distributed in the developing and adult nervous system. In order to further determine the neural functions of TGF-beta, we have localized the TGF-beta isoforms 1, 2 and 3 in the adult rat adrenal medulla and studied the neuroprotective capacity of one representative family member, TGF-beta 2, for those spinal cord neurons which innervate adrenal chromaffin cells and which die after destruction of the adrenal medulla. Unilateral electrothermal destruction of the adrenal medulla led to the disappearance of 25% of sympathetic preganglionic neurons, which are located in the intermediolateral (IML) column of thoracic spinal cord segments 7-10 and can be selectively marked by NADPH-diaphorase. The neurons which disappeared following adrenomedullectomy constitute the full set of neurons that innervate the adrenal medulla. Implantation of gelfoam soaked with 0.5 micrograms TGF-beta 2 into the adrenal wound cavity rescued all spinal cord neurons in the IML ipsilaterally to the lesioned side. Cytochrome c was not effective. Injections of [125I]TGF-beta 2 into the adrenal medulla did not result in retrograde transport and subsequent labelling of spinal cord neurons, suggesting that TGF-beta may exert its neuroprotective actions by indirect mechanisms. TGF-beta applied to cultured adrenocortical cells did not overtly increase the amount of mRNA for fibroblast growth factor-2, an established trophic molecule for sympathetic preganglionic spinal cord neurons. The mechanisms by which TGF-beta exerts its neurotrophic effect are therefore unclear. Even so, our data provide the first evidence that TGF-beta may play an important role in vivo in the control of maintenance of a population of spinal cord neurons.
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PMID:TGF-beta rescues target-deprived preganglionic sympathetic neurons in the spinal cord. 871 64

Purposes of this work were to examine the plausible down-regulation of porcine heart diaphorase (PHD) enzyme reactivity and nitric oxide synthase (NOS) enzyme reactivity by trimanganese hexakis(3,5-diisopropylsalicylate), [Mn(3)(3,5-DIPS)(6)] as well as dicopper tetrakis(3,5- diisopropylsalicylate, [Cu(II)(2)(3,5-DIPS)(4)] as a mechanistic accounting for their pharmacological activities.Porcine heart disease was found to oxidize 114 muM reduced nicotinamide-adenine- dinucleotide-'(3)-phosphate (NADPH) with a corresponding reduction of an equivalent concentration of 2,6-dichlorophenolindophenol (DCPIP). As reported for Cu(II)(2) (3,5-DIPS)(4), addition of Mn(3)(3,5-DIPS)(6) to this reaction mixture decreased the reduction of DCPIP without significantly affecting the oxidation of NADPH. The concentration of Mn(3)(3,5-DIPS)(6) that produced a 50% decrease in DCPIP reduction (IC(50)) was found to be 5muM. Mechanistically, this inhibition of DCPIP reduction with ongoing NADPH oxidation by PHD was found to be due to the ability of Mn(3)(3,5-DIPS)(6) to serve as a catalytic electron acceptor for reduced PHD as had been reported for Cu(II)(2)(3,5-DIPS)(4). This catalytic decrease in reduction of DCPIP by Mn(3)(3,5-DIPS)(6) was enhanced by the presence of a large concentration of DCPIP and decreased by the presence of a large concentration of NADPH, consistent with what had been observed for the activity of Cu(II)(2)(3,5-DIPS)(4)Oxidation of NADPH by PHD in the presence of Mn(3)(3,5-DIPS)(6) and the absence of DCPIP was linearly related to the concentration of added Mn(3)(3,5-DIPS)(6) through the concentration range of 2.4 muM to 38muM with a 50% recovery of NADPH oxidation by PHD at a concentration of 6 muM Mn(3)(3,5-DIPS)(6)Conversion of [(3)H] L-Arginine to [(3)H] L-Citrulline by purified rat brain nitric oxide synthase (NOS) was decreased in a concentrated related fashion with the addition of Mn(3)(3,5-DIPS)(6) as well as Cu(II)(2)(3,5-DIPS)(4) which is an extention of results reported earlier for Cu(II)(2)(3,5-DIPS)(4). The concentration of these two compounds required to produce a 50% decrease in L-Citrulline synthesis by NOS, which may be due to down-regulation of NOS, were 0.1 mM and 8muM respectively, consistent with the relative potencies of these two complexes in preventing the reduction of Cytochrome c by NOS.It is concluded that Mn(3)(3,5-DIPS)(6), as has been reported for Cu(II)(2) (3,5-DIPS)(4) , serves as an electron acceptor in down-regulating PHD and both of these complexes down-regulate rat brain NOS reactivity. A decrease in NO synthesis in animal models of seizure and radiation injury may account for the anticonvulsant, radioprotectant, and radiorecovery activities of Mn(3)(3,5-DIPS)(6) and Cu(II)(2)(3,5-DIPS)(4).
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PMID:Down-Regulation of Porcine Heart Diaphorase Reactivity by Trimanganese Hexakis(3,5-Diisopropylsalicylate), Mn(3)(3,5-DIPS)6, and Down-Regulation of Nitric Oxide Synthase Reactivity by Mn(3)(3,5-DIPS)(6) and Cu(II)(2)(3,5-DIPS)(4). 1847 89